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Sample records for aldehyde dehydrogenase aldh

  1. The roles of aldehyde dehydrogenases (ALDHs in the PDH bypass of Arabidopsis

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    Lin Ming

    2009-03-01

    Full Text Available Abstract Background Eukaryotic aldehyde dehydrogenases (ALDHs, EC 1.2.1, which oxidize aldehydes into carboxylic acids, have been classified into more than 20 families. In mammals, Family 2 ALDHs detoxify acetaldehyde. It has been hypothesized that plant Family 2 ALDHs oxidize acetaldehyde generated via ethanolic fermentation, producing acetate for acetyl-CoA biosynthesis via acetyl-CoA synthetase (ACS, similar to the yeast pathway termed the "pyruvate dehydrogenase (PDH bypass". Evidence for this pathway in plants has been obtained from pollen. Results To test for the presence of the PDH bypass in the sporophytic tissue of plants, Arabidopsis plants homozygous for mutant alleles of all three Family 2 ALDH genes were fed with 14C-ethanol along with wild type controls. Comparisons of the incorporation rates of 14C-ethanol into fatty acids in mutants and wild type controls provided direct evidence for the presence of the PDH bypass in sporophytic tissue. Among the three Family 2 ALDHs, one of the two mitochondrial ALDHs (ALDH2B4 appears to be the primary contributor to this pathway. Surprisingly, single, double and triple ALDH mutants of Arabidopsis did not exhibit detectable phenotypes, even though a Family 2 ALDH gene is required for normal anther development in maize. Conclusion The PDH bypass is active in sporophytic tissue of plants. Blocking this pathway via triple ALDH mutants does not uncover obvious visible phenotypes.

  2. Cloning and molecular evolution of the aldehyde dehydrogenase 2 gene (Aldh2) in bats (Chiroptera).

    Science.gov (United States)

    Chen, Yao; Shen, Bin; Zhang, Junpeng; Jones, Gareth; He, Guimei

    2013-02-01

    Old World fruit bats (Pteropodidae) and New World fruit bats (Phyllostomidae) ingest significant quantities of ethanol while foraging. Mitochondrial aldehyde dehydrogenase (ALDH2, encoded by the Aldh2 gene) plays an important role in ethanol metabolism. To test whether the Aldh2 gene has undergone adaptive evolution in frugivorous and nectarivorous bats in relation to ethanol elimination, we sequenced part of the coding region of the gene (1,143 bp, ~73 % coverage) in 14 bat species, including three Old World fruit bats and two New World fruit bats. Our results showed that the Aldh2 coding sequences are highly conserved across all bat species we examined, and no evidence of positive selection was detected in the ancestral branches leading to Old World fruit bats and New World fruit bats. Further research is needed to determine whether other genes involved in ethanol metabolism have been the targets of positive selection in frugivorous and nectarivorous bats.

  3. Aldehyde Dehydrogenase-2 (ALDH2) Ameliorates Chronic Alcohol Ingestion-Induced Myocardial Insulin Resistance and Endoplasmic Reticulum Stress

    OpenAIRE

    Li, Shi-Yan; Gilbert, Sara A. B.; Li, Qun; Ren, Jun

    2009-01-01

    Chronic alcohol intake leads to insulin resistance and alcoholic cardiomyopathy, which appears to be a result of the complex interaction between genes and environment. This study was designed to examine the impact of aldehyde dehydrogenase-2 (ALDH2) transgenic overexpression on alcohol-induced insulin resistance and myocardial injury. ALDH2 transgenic mice were produced using chicken β-actin promoter. Wild-type FVB and ALDH2 mice were fed a 4% alcohol or control diet for 12 wks. Cell shorteni...

  4. The activity of alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) in the sera of patients with brain cancer.

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    Jelski, Wojciech; Laniewska-Dunaj, Magdalena; Orywal, Karolina; Kochanowicz, Jan; Rutkowski, Robert; Szmitkowski, Maciej

    2014-12-01

    Human brain tissue contains various alcohol dehydrogenase (ADH) isoenzymes and possess also aldehyde dehydrogenase (ALDH) activity. In our last experiments we have shown that ADH and ALDH are present also in the brain tumour cells. Moreover the activities of total ADH and class I isoenzymes were significantly higher in cancer tissue than healthy cells. It can suggests that these changes may be reflected by enzyme activity in the serum of patients with brain cancer. Serum samples were taken for routine biochemical investigation from 62 patients suffering from brain cancer (36 glioblastoma, 26 meningioma). For the measurement of the activity of class I and II ADH isoenzymes and ALDH activity, the fluorometric methods were used. The total ADH activity and activity of class III and IV isoenzymes were measured by the photometric method. A statistically significant increase of class I alcohol dehydrogenase isoenzymes was found in the sera of patients with brain cancer. The median activity of this class isoenzyme in the patients group increased about 24 % in the comparison to the control level. The total alcohol dehydrogenase activity was also significantly higher (26 %) among patients with brain tumour than healthy ones. The activities of other tested ADH isoenzymes and total ALDH were unchanged. The increase of the activity of total ADH and class I alcohol dehydrogenase isoenzyme in the sera of patients with brain cancer seems to be caused by the release of this isoenzyme from tumour's cells.

  5. Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1, in human epithelial cancers.

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    Shan Deng

    Full Text Available Aldehyde dehydrogenase isoform 1 (ALDH1 has been proved useful for the identification of cancer stem cells. However, our knowledge of the expression and activity of ALDH1 in common epithelial cancers and their corresponding normal tissues is still largely absent. Therefore, we characterized ALDH1 expression in 24 types of normal tissues and a large collection of epithelial tumor specimens (six cancer types, n = 792 by immunohistochemical staining. Using the ALDEFUOR assay, ALDH1 activity was also examined in 16 primary tumor specimens and 43 established epithelial cancer cell lines. In addition, an ovarian cancer transgenic mouse model and 7 murine ovarian cancer cell lines were analyzed. We found that the expression levels and patterns of ALDH1 in epithelial cancers are remarkably distinct, and they correlate with their corresponding normal tissues. ALDH1 protein expression levels are positively correlated with ALDH1 enzymatic activity measured by ALDEFLUOR assay. Long-term in vitro culture doesn't significantly affect ALDH1 activity in epithelial tumor cells. Consistent with research on other cancers, we found that high ALDH1 expression is significantly associated with poor clinical outcomes in serous ovarian cancer patients (n = 439, p = 0.0036. Finally, ALDH(br tumor cells exhibit cancer stem cell properties and are resistant to chemotherapy. As a novel cancer stem cell marker, ALDH1 can be used for tumors whose corresponding normal tissues express ALDH1 in relatively restricted or limited levels such as breast, lung, ovarian or colon cancer.

  6. Modeling-dependent protein characterization of the rice aldehyde dehydrogenase (ALDH superfamily reveals distinct functional and structural features.

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    Simeon O Kotchoni

    Full Text Available The completion of the rice genome sequence has made it possible to identify and characterize new genes and to perform comparative genomics studies across taxa. The aldehyde dehydrogenase (ALDH gene superfamily encoding for NAD(P(+-dependent enzymes is found in all major plant and animal taxa. However, the characterization of plant ALDHs has lagged behind their animal- and prokaryotic-ALDH homologs. In plants, ALDHs are involved in abiotic stress tolerance, male sterility restoration, embryo development and seed viability and maturation. However, there is still no structural property-dependent functional characterization of ALDH protein superfamily in plants. In this paper, we identify members of the rice ALDH gene superfamily and use the evolutionary nesting events of retrotransposons and protein-modeling-based structural reconstitution to report the genetic and molecular and structural features of each member of the rice ALDH superfamily in abiotic/biotic stress responses and developmental processes. Our results indicate that rice-ALDHs are the most expanded plant ALDHs ever characterized. This work represents the first report of specific structural features mediating functionality of the whole families of ALDHs in an organism ever characterized.

  7. Effect of the allelic variants of aldehyde dehydrogenase ALDH2*2 and alcohol dehydrogenase ADH1B*2 on blood acetaldehyde concentrations

    OpenAIRE

    Peng Giia-Sheun; Yin Shih-Jiun

    2009-01-01

    Abstract Alcoholism is a complex behavioural disorder. Molecular genetics studies have identified numerous candidate genes associated with alcoholism. It is crucial to verify the disease susceptibility genes by correlating the pinpointed allelic variations to the causal phenotypes. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes responsible for ethanol metabolism in humans. Both ADH and ALDH exhibit functional polymorphisms among racial populations; the...

  8. The diagnostic value of alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) measurement in the sera of gastric cancer patients.

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    Jelski, Wojciech; Orywal, Karolina; Laniewska, Magdalena; Szmitkowski, Maciej

    2010-12-01

    Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are present in gastric cancer cells (GC). Moreover, the activity of total ADH and class IV isoenzymes is significantly higher in cancer tissue than in healthy mucosa. The activity of these enzymes in cancer cells is probably reflected in the sera and could thus be helpful for diagnostics of gastric cancer. The aim of this study was to investigate a potential role of ADH and ALDH as tumor markers for gastric cancer. We defined diagnostic sensitivity, specificity, predictive value for positive and negative results, and receiver-operating characteristics (ROC) curve for tested enzymes. Serum samples were taken from 168 patients with gastric cancer before treatment and from 168 control subjects. Total ADH activity and class III and IV isoenzymes were measured by photometric but ALDH activity and ADH I and II by the fluorometric method, with class-specific fluorogenic substrates. There was significant increase in the activity of ADH IV isoenzyme and ADH total in the sera of gastric cancer patients compared to the control. The diagnostic sensitivity for ADH IV was 73%, specificity 79%, positive and negative predictive values were 81 and 72% respectively. Area under ROC curve for ADH IV was 0.67. The results suggest a potential role for ADH IV as marker of gastric cancer.

  9. Pharmacological recruitment of aldehyde dehydrogenase 3A1 (ALDH3A1) to assist ALDH2 in acetaldehyde and ethanol metabolism in vivo

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    Chen, Che-Hong; Cruz, Leslie A.; Mochly-Rosen, Daria

    2015-01-01

    Correcting a genetic mutation that leads to a loss of function has been a challenge. One such mutation is in aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2. This mutation is present in ∼0.6 billion East Asians and results in accumulation of toxic acetaldehyde after consumption of ethanol. To temporarily increase metabolism of acetaldehyde in vivo, we describe an approach in which a pharmacologic agent recruited another ALDH to metabolize acetaldehyde. We focused on ALDH3A1, which is enriched in the upper aerodigestive track, and identified Alda-89 as a small molecule that enables ALDH3A1 to metabolize acetaldehyde. When given together with the ALDH2-specific activator, Alda-1, Alda-89 reduced acetaldehyde-induced behavioral impairment by causing a rapid reduction in blood ethanol and acetaldehyde levels after acute ethanol intoxication in both wild-type and ALDH2-deficient, ALDH2*1/*2, heterozygotic knock-in mice. The use of a pharmacologic agent to recruit an enzyme to metabolize a substrate that it usually does not metabolize may represent a novel means to temporarily increase elimination of toxic agents in vivo. PMID:25713355

  10. Genome-wide identification and analysis of the aldehyde dehydrogenase (ALDH) gene superfamily in apple (Malus × domestica Borkh.).

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    Li, Xiaoqin; Guo, Rongrong; Li, Jun; Singer, Stacy D; Zhang, Yucheng; Yin, Xiangjing; Zheng, Yi; Fan, Chonghui; Wang, Xiping

    2013-10-01

    Aldehyde dehydrogenases (ALDHs) represent a protein superfamily encoding NAD(P)(+)-dependent enzymes that oxidize a wide range of endogenous and exogenous aliphatic and aromatic aldehydes. In plants, they are involved in many biological processes and play a role in the response to environmental stress. In this study, a total of 39 ALDH genes from ten families were identified in the apple (Malus × domestica Borkh.) genome. Synteny analysis of the apple ALDH (MdALDH) genes indicated that segmental and tandem duplications, as well as whole genome duplications, have likely contributed to the expansion and evolution of these gene families in apple. Moreover, synteny analysis between apple and Arabidopsis demonstrated that several MdALDH genes were found in the corresponding syntenic blocks of Arabidopsis, suggesting that these genes appeared before the divergence of lineages that led to apple and Arabidopsis. In addition, phylogenetic analysis, as well as comparisons of exon-intron and protein structures, provided further insight into both their evolutionary relationships and their putative functions. Tissue-specific expression analysis of the MdALDH genes demonstrated diverse spatiotemporal expression patterns, while their expression profiles under abiotic stress and various hormone treatments indicated that many MdALDH genes were responsive to high salinity and drought, as well as different plant hormones. This genome-wide identification, as well as characterization of evolutionary relationships and expression profiles, of the apple MdALDH genes will not only be useful for the further analysis of ALDH genes and their roles in stress response, but may also aid in the future improvement of apple stress tolerance.

  11. Androgen regulation of aldehyde dehydrogenase 1A3 (ALDH1A3) in androgen responsive human prostate cancer cell LNCaP.

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    Previous gene array data from our laboratory identified the retinoic acid (RA) biosynthesis enzyme aldehyde dehydrogenase 1A3 (ALDH1A3) as a putative androgen-responsive gene in prostate cancer epithelial cells (LNCaP). In the present study we attempted to identify if any of the three ALDH1A/RA synt...

  12. The activity of class I, II, III and IV of alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) in brain cancer.

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    Laniewska-Dunaj, Magdalena; Jelski, Wojciech; Orywal, Karolina; Kochanowicz, Jan; Rutkowski, Robert; Szmitkowski, Maciej

    2013-07-01

    The brain being highly sensitive to the action of alcohol is potentially susceptible to its carcinogenic effects. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the main enzymes involved in ethanol metabolism, which leads to the generation of carcinogenic acetaldehyde. Human brain tissue contains various ADH isoenzymes and possess also ALDH activity. The purpose of this study was to compare the capacity for ethanol metabolism measured by ADH isoenzymes and ALDH activity in cancer tissues and healthy brain cells. The samples were taken from 62 brain cancer patients (36 glioblastoma, 26 meningioma). For the measurement of the activity of class I and II ADH isoenzymes and ALDH activity, the fluorometric methods were used. The total ADH activity and activity of class III and IV isoenzymes were measured by the photometric method. The total activity of ADH, and activity of class I ADH were significantly higher in cancer cells than in healthy tissues. The other tested classes of ADH and ALDH did not show statistically significant differences of activity in cancer and in normal cells. Analysis of the enzymes activity did not show significant differences depending on the location of the tumor. The differences in the activity of total alcohol dehydrogenase, and class I isoenzyme between cancer tissues and healthy brain cells might be a factor for metabolic changes and disturbances in low mature cancer cells and additionally might be a reason for higher level of acetaldehyde which can intensify the carcinogenesis.

  13. Transcriptional Regulation of Expression of the Maize Aldehyde Dehydrogenase 7 Gene (ZmALDH7B6) in Response to Abiotic Stresses

    Institute of Scientific and Technical Information of China (English)

    GU Ri-liang

    2014-01-01

    Aldehyde dehydrogenases (ALDHs) represent a large protein family, which includes several members that catalyze the oxidation of an aldehyde to its corresponding carboxylic acid in plants. Genes encoding members of theALDH7 subfamily have been suggested to play important roles in various stress adaptations in plants. In this study, quantitative RT-PCR analysis revealed that a maizeALDH7 subfamily member (ZmALDH7B6) was constitutively expressed in various organs, including roots, leaves, immature ears, tassels, and developing seeds. The abundance ofZmALDH7B6 mRNA transcripts in maize roots was increased by ammonium, NaCl, and mannitol treatments. To further analyze tissue-speciifc and stress-induced expression patterns, the 1.5-kb 5´-lfankingZmALDH7B6 promoter region was fused to the β-glucuronidase (GUS) reporter gene and introduced into maize plants. In roots of independent transgenic lines, there was signiifcant induction of GUS activity in response to ammonium supply, conifrming ammonium-dependent expression ofZmALDH7B6 at the transcript level. Histochemical staining showed that GUS activity driven by theZmALDH7B6 promoter was mainly localized in the vascular tissues of maize roots. These results suggested thatZmALDH7B6 is induced by multiple environmental stresses in maize roots, and may play a role in detoxifying aldehydes, particularly in vascular tissue.

  14. Differential expression of aldehyde dehydrogenase 1a1 (ALDH1 in normal ovary and serous ovarian tumors

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    Penumatsa Krishna

    2010-12-01

    Full Text Available Abstract Background We showed there are specific ALDH1 autoantibodies in ovarian autoimmune disease and ovarian cancer, suggesting a role for ALDH1 in ovarian pathology. However, there is little information on the ovarian expression of ALDH1. Therefore, we compared ALDH1 expression in normal ovary and benign and malignant ovarian tumors to determine if ALDH1 expression is altered in ovarian cancer. Since there is also recent interest in ALDH1 as a cancer stem cell (CSC marker, we assessed co-expression of ALDH1 with CSC markers in order to determine if ALDH1 is a potential CSC marker in ovarian cancer. Methods mRNA and protein expression were compared in normal human ovary and serous ovarian tumors using quantitative Reverse-Transcriptase PCR, Western blot (WB and semi-quantitative immunohistochemistry (IHC. ALDH1 enzyme activity was confirmed in primary ovarian cells by flow cytometry (FC using ALDEFLUOR assay. Results ALDH1 mRNA expression was significantly reduced (p Conclusions Total ALDH1 expression is significantly reduced in malignant ovarian tumors while it is relatively unchanged in benign tumors compared to normal ovary. Thus, ALDH1 expression in the ovary does not appear to be similar to breast, lung or colon cancer suggesting possible functional differences in these cancers. Significance These observations suggest that reduced ALDH1 expression is associated with malignant transformation in ovarian cancer and provides a basis for further study of the mechanism of ALDH1 in this process.

  15. Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human large bowel: association of the functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal cancer.

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    Chiang, Chien-Ping; Jao, Shu-Wen; Lee, Shiao-Pieng; Chen, Pei-Chi; Chung, Chia-Chi; Lee, Shou-Lun; Nieh, Shin; Yin, Shih-Jiun

    2012-02-01

    Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for metabolism of ethanol. Functional polymorphisms of ADH1B, ADH1C, and ALDH2 genes occur among racial populations. The goal of this study was to systematically determine the functional expressions and cellular localization of ADHs and ALDHs in human rectal mucosa, the lesions of adenocarcinoma and hemorrhoid, and the genetic association of allelic variations of ADH and ALDH with large bowel disorders. Twenty-one surgical specimens of rectal adenocarcinoma and the adjacent normal mucosa, including 16 paired tissues of rectal tumor, normal mucosae of rectum and sigmoid colon from the same individuals, and 18 surgical mixed hemorrhoid specimens and leukocyte DNA samples from 103 colorectal cancer patients, 67 hemorrhoid patients, and 545 control subjects recruited in previous study, were investigated. The isozyme/allozyme expression patterns of ADH and ALDH were identified by isoelectric focusing and the activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting using the corresponding purified class-specific antibodies; the cellular activity and protein localizations were detected by immunohistochemistry and histochemistry, respectively. Genotypes of ADH1B, ADH1C, and ALDH2 were determined by polymerase chain reaction-restriction fragment length polymorphisms. At 33mM ethanol, pH 7.5, the activity of ADH1C*1/1 phenotypes exhibited 87% higher than that of the ADH1C*1/*2 phenotypes in normal rectal mucosa. The activity of ALDH2-active phenotypes of rectal mucosa was 33% greater than ALDH2-inactive phenotypes at 200μM acetaldehyde. The protein contents in normal rectal mucosa were in the following order: ADH1>ALDH2>ADH3≈ALDH1A1, whereas those of ADH2, ADH4, and ALDH3A1 were fairly low. Both activity and content of ADH1 were significantly decreased in rectal tumors, whereas the ALDH activity remained

  16. Stem cell marker aldehyde dehydrogenase 1 (ALDH1)-expressing cells are enriched in triple-negative breast cancer.

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    Li, Huihui; Ma, Fei; Wang, Haijuan; Lin, Chen; Fan, Ying; Zhang, Xueyan; Qian, Haili; Xu, Binghe

    2013-12-17

    The stem cell marker ALDH1 has been of particular interest to scientists since it has been successfully used as a marker to isolate cancer stem cells from breast cancers. However, little is known, especially in Chinese breast cancer patients, on whether ALDH1 enrichment is prevalent in certain subtypes of breast cancer. In this study, we performed flow cytometry and immunohistochemistry to measure the expression of ALDH1 in 10 breast cancer cell lines and in a set of tissue microarrays consisting of 101 breast cancer tissues from the Chinese population. The 101 breast cancer tissues included 4 cancer subtypes defined on bases of their ER, PR, and HER2 statuses: triple-negative (25 cases), luminal A (33 cases), luminal B (16 cases) and HER2-overexpressing (HER2-OE, 27 cases). We found that ALDH1 was expressed in 25 of the 101 cases of breast cancer tissues. When the analysis was stratified, we found that the expression of ALDH1 varied significantly among the 4 subtypes, with a higher expression in triple-negative breast cancer (TNBC, p=0.003) than in the other 3 subtypes. In a series of breast cancer cell lines, we also confirmed that ALDH1 activity was mainly found in TNBC cell lines compared with non-TNBC ones (15.6% ± 2.45% vs 5.5% ± 2.58%, p=0.026). These data support the concept that the expression of ALDH1 is higher in TNBC than non-TNBC, which may be clinically meaningful for a better understanding of the poor prognosis of TNBC patients.

  17. Characterization of the rat Class 3 aldehyde dehydrogenase gene promoter.

    OpenAIRE

    Xie, Y Q; Takimoto, K; Pitot, H. C.; Miskimins, W K; Lindahl, R

    1996-01-01

    The Class 3 aldehyde dehydrogenase gene (ALDH-3) is differentially expressed. Expression is either constitutive or xenobiotic inducible via an aromatic hydrocarbon (Ah) receptor-mediated pathway, depending upon the tissue. A series of studies were performed to examine the regulation of rat ALDH-3 basal expression. DNase I footprint analysis identified four DNA regions within the proximal 1 kb of the 5' flanking region of rat ALDH-3 which interact with regulatory proteins. Reporter gene and ge...

  18. The Genetics of Alcohol Metabolism: Role of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Variants

    OpenAIRE

    Edenberg, Howard J

    2007-01-01

    The primary enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both enzymes occur in several forms that are encoded by different genes; moreover, there are variants (i.e., alleles) of some of these genes that encode enzymes with different characteristics and which have different ethnic distributions. Which ADH or ALDH alleles a person carries influence his or her level of alcohol consumption and risk of alcoholism. Researchers to date pri...

  19. Mitochondrial aldehyde dehydrogenase 2 protects gastric mucosa cells against DNA damage caused by oxidative stress.

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    Duan, Yantao; Gao, Yaohui; Zhang, Jun; Chen, Yinan; Jiang, Yannan; Ji, Jun; Zhang, Jianian; Chen, Xuehua; Yang, Qiumeng; Su, Liping; Zhang, Jun; Liu, Bingya; Zhu, Zhenggang; Wang, Lishun; Yu, Yingyan

    2016-04-01

    Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a member of the aldehyde dehydrogenase superfamily and is involved with the metabolic processing of aldehydes. ALDH2 plays a cytoprotective role by removing aldehydes produced during normal metabolism. We examined the cytoprotective role of ALDH2 specifically in gastric mucosa cells. Overexpression of ALDH2 increased the viability of gastric mucosa cells treated with H2O2, while knockdown of ALDH2 had an opposite effect. Moreover, overexpression of ALDH2 protected gastric mucosa cells against oxidative stress-induced apoptosis as determined by flow cytometry, Hoechst 33342, and TUNEL assays. Consistently, ALDH2 knockdown had an opposite effect. Additionally, DNA damage was ameliorated in ALDH2-overexpressing gastric mucosa cells treated with H2O2. We further identified that this cytoprotective role of ALDH2 was mediated by metabolism of 4-hydroxynonenal (4-HNE). Consistently, 4-HNE mimicked the oxidative stress induced by H2O2 in gastric mucosa cells. Treatment with 4-HNE increased levels of DNA damage in ALDH2-knockdown GES-1 cells, while overexpression of ALDH2 decreased 4-HNE-induced DNA damage. These findings suggest that ALDH2 can protect gastric mucosa cells against DNA damage caused by oxidative stress by reducing levels of 4-HNE.

  20. Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoid-dependent axial patterning in metazoans.

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    Sobreira, Tiago J P; Marlétaz, Ferdinand; Simões-Costa, Marcos; Schechtman, Deborah; Pereira, Alexandre C; Brunet, Frédéric; Sweeney, Sarah; Pani, Ariel; Aronowicz, Jochanan; Lowe, Christopher J; Davidson, Bradley; Laudet, Vincent; Bronner, Marianne; de Oliveira, Paulo S L; Schubert, Michael; Xavier-Neto, José

    2011-01-01

    Aldehyde dehydrogenases (ALDHs) catabolize toxic aldehydes and process the vitamin A-derived retinaldehyde into retinoic acid (RA), a small diffusible molecule and a pivotal chordate morphogen. In this study, we combine phylogenetic, structural, genomic, and developmental gene expression analyses to examine the evolutionary origins of ALDH substrate preference. Structural modeling reveals that processing of small aldehydes, such as acetaldehyde, by ALDH2, versus large aldehydes, including retinaldehyde, by ALDH1A is associated with small versus large substrate entry channels (SECs), respectively. Moreover, we show that metazoan ALDH1s and ALDH2s are members of a single ALDH1/2 clade and that during evolution, eukaryote ALDH1/2s often switched between large and small SECs after gene duplication, transforming constricted channels into wide opened ones and vice versa. Ancestral sequence reconstructions suggest that during the evolutionary emergence of RA signaling, the ancestral, narrow-channeled metazoan ALDH1/2 gave rise to large ALDH1 channels capable of accommodating bulky aldehydes, such as retinaldehyde, supporting the view that retinoid-dependent signaling arose from ancestral cellular detoxification mechanisms. Our analyses also indicate that, on a more restricted evolutionary scale, ALDH1 duplicates from invertebrate chordates (amphioxus and ascidian tunicates) underwent switches to smaller and narrower SECs. When combined with alterations in gene expression, these switches led to neofunctionalization from ALDH1-like roles in embryonic patterning to systemic, ALDH2-like roles, suggesting functional shifts from signaling to detoxification. PMID:21169504

  1. Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring

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    Ahadome, Sarah D.; Abraham, David J.; Rayapureddi, Suryanarayana; Saw, Valerie P.; Saban, Daniel R.; Calder, Virginia L.; Norman, Jill T.; Ponticos, Markella; Daniels, Julie T.; Dart, John K.

    2016-01-01

    Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. Aldehyde dehydrogenase family 1 (ALDH1) is upregulated in both ocular MMP (OMMP) conjunctiva and cultured fibroblasts. Application of the ALDH metabolite, retinoic acid (RA), to normal human conjunctival fibroblasts in vitro induced a diseased phenotype. Conversely, application of ALDH inhibitors, including disulfiram, to OMMP fibroblasts in vitro restored their functionality to that of normal controls. ALDH1 is also upregulated in the mucosa of the mouse model of scarring allergic eye disease (AED), used here as a surrogate for OMMP, in which topical application of disulfiram decreased fibrosis in vivo. These data suggest that progressive scarring in OMMP results from ALDH/RA fibroblast autoregulation, that the ALDH1 subfamily has a central role in immune-mediated ocular mucosal scarring, and that ALDH inhibition with disulfiram is a potential and readily translatable antifibrotic therapy. PMID:27699226

  2. Alcohol and Aldehyde Dehydrogenases: Retinoid Metabolic Effects in Mouse Knockout Models

    OpenAIRE

    Kumar, Sandeep; Sandell, Lisa L.; Trainor, Paul A; Koentgen, Frank; Duester, Gregg

    2011-01-01

    Retinoic acid (RA) is the active metabolite of vitamin A (retinol) that controls growth and development. The first step of RA synthesis is controlled by enzymes of the alcohol dehydrogenase (ADH) and retinol dehydrogenase (RDH) families that catalyze oxidation of retinol to retinaldehyde. The second step of RA synthesis is controlled by members of the aldehyde dehydrogenase (ALDH) family also known as retinaldehyde dehydrogenase (RALDH) that further oxidize retinaldehyde to produce RA. RA fun...

  3. Identification and characterisation of Aedes aegypti aldehyde dehydrogenases involved in pyrethroid metabolism.

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    Nongkran Lumjuan

    Full Text Available Pyrethroid insecticides, especially permethrin and deltamethrin, have been used extensively worldwide for mosquito control. However, insecticide resistance can spread through a population very rapidly under strong selection pressure from insecticide use. The upregulation of aldehyde dehydrogenase (ALDH has been reported upon pyrethroid treatment. In Aedes aegypti, the increase in ALDH activity against the hydrolytic product of pyrethroid has been observed in DDT/permethrin-resistant strains. The objective of this study was to identify the role of individual ALDHs involved in pyrethroid metabolism.Three ALDHs were identified; two of these, ALDH9948 and ALDH14080, were upregulated in terms of both mRNA and protein levels in a DDT/pyrethroid-resistant strain of Ae. aegypti. Recombinant ALDH9948 and ALDH14080 exhibited oxidase activities to catalyse the oxidation of a permethrin intermediate, phenoxybenzyl aldehyde (PBald, to phenoxybenzoic acid (PBacid.ALDHs have been identified in association with permethrin resistance in Ae. aegypti. Characterisation of recombinant ALDHs confirmed the role of this protein in pyrethroid metabolism. Understanding the biochemical and molecular mechanisms of pyrethroid resistance provides information for improving vector control strategies.

  4. Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

    DEFF Research Database (Denmark)

    Ferrari, P.; McKay, J. D.; Jenab, M.;

    2012-01-01

    BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populati......BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian...

  5. Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use–dependent inhibitor of dopamine synthesis

    OpenAIRE

    Yao, Lina; Fan, Peidong; Arolfo, Maria; Jiang, Zhang; Olive, M. Foster; Zablocki, Jeff; Sun, Hai-Ling; Chu, Nancy; Lee, Jeongrim; Kim, Hee-Yong; Leung, Kwan; Shryock, John; Blackburn, Brent; Diamond, Ivan

    2010-01-01

    There is no effective treatment for cocaine addiction despite extensive knowledge of the neurobiology of drug addiction1–4. Here we show that a selective aldehyde dehydrogenase-2 (ALDH-2) inhibitor, ALDH2i, suppresses cocaine self-administration in rats and prevents cocaine- or cue-induced reinstatement in a rat model of cocaine relapse-like behavior. We also identify a molecular mechanism by which ALDH-2 inhibition reduces cocaine-seeking behavior: increases in tetrahydropapaveroline (THP) f...

  6. Cloning and heterologous expression of two aryl-aldehyde dehydrogenases from the white-rot basidiomycete Phanerochaete chrysosporium

    International Nuclear Information System (INIS)

    We identified two aryl-aldehyde dehydrogenase proteins (PcALDH1 and PcALDH2) from the white-rot basidiomycete Phanerochaete chrysosporium. Both PcALDHs were translationally up-regulated in response to exogenous addition of vanillin, one of the key aromatic compounds in the pathway of lignin degradation by basidiomycetes. To clarify the catalytic functions of PcALDHs, we isolated full-length cDNAs encoding these proteins and heterologously expressed the recombinant enzymes using a pET/Escherichia coli system. The open reading frames of both PcALDH1 and PcALDH2 consisted of 1503 nucleotides. The deduced amino acid sequences of both proteins showed high homologies with aryl-aldehyde dehydrogenases from other organisms and contained ten conserved domains of ALDHs. Moreover, a novel glycine-rich motif 'GxGxxxG' was located at the NAD+-binding site. The recombinant PcALDHs catalyzed dehydrogenation reactions of several aryl-aldehyde compounds, including vanillin, to their corresponding aromatic acids. These results strongly suggested that PcALDHs metabolize aryl-aldehyde compounds generated during fungal degradation of lignin and various aromatic xenobiotics.

  7. Cloning and heterologous expression of two aryl-aldehyde dehydrogenases from the white-rot basidiomycete Phanerochaete chrysosporium

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Tomofumi [Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Fukuoka Institute of Health and Environmental Sciences, 39 Mukaizano, Dazaifu-shi, Fukuoka 818-0135 (Japan); Ichinose, Hirofumi [Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Wariishi, Hiroyuki, E-mail: hirowari@agr.kyushu-u.ac.jp [Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Bio-Architecture Center, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Innovation Center for Medical Redox Navigation, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan)

    2010-04-09

    We identified two aryl-aldehyde dehydrogenase proteins (PcALDH1 and PcALDH2) from the white-rot basidiomycete Phanerochaete chrysosporium. Both PcALDHs were translationally up-regulated in response to exogenous addition of vanillin, one of the key aromatic compounds in the pathway of lignin degradation by basidiomycetes. To clarify the catalytic functions of PcALDHs, we isolated full-length cDNAs encoding these proteins and heterologously expressed the recombinant enzymes using a pET/Escherichia coli system. The open reading frames of both PcALDH1 and PcALDH2 consisted of 1503 nucleotides. The deduced amino acid sequences of both proteins showed high homologies with aryl-aldehyde dehydrogenases from other organisms and contained ten conserved domains of ALDHs. Moreover, a novel glycine-rich motif 'GxGxxxG' was located at the NAD{sup +}-binding site. The recombinant PcALDHs catalyzed dehydrogenation reactions of several aryl-aldehyde compounds, including vanillin, to their corresponding aromatic acids. These results strongly suggested that PcALDHs metabolize aryl-aldehyde compounds generated during fungal degradation of lignin and various aromatic xenobiotics.

  8. Polymorphisms of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 and colorectal cancer risk in Chinese males

    Institute of Scientific and Technical Information of China (English)

    Chang-Ming Gao; Keitaro Matsuo; Nobuyuki Hamajima; Kazuo Tajima; Toshiro Takezaki; Jian-Zhong Wu; Xiao-Mei Zhang; Hai-Xia Cao; Jian-Hua Ding; Yan-Ting Liu; Su-Ping Li; Jia Cao

    2008-01-01

    AIM: To evaluate the relationship between drinking and polymorphisms of alcohol dehydrogenase 2 (ADH2) and/or aldehyde dehydrogenase 2 (ALDH2) for risk of colorectal cancer (CRC) in Chinese males.METHODS: A case-control study was conducted in 190 cases and 223 population-based controls.ADH2 Arg47His (G-A) and ALDH2 Glu487Lys (G-A) genotypes were identified by PCR and denaturing high-performance liquid chromatography (DHPLC).Information on smoking and drinking was collected and odds ratio (OR) was estimated.RESULTS: The ADH2 A/A and ALDH2 G/G genotypes showed moderately increased CRC risk. The age- and smoking-adjusted OR for ADH2 A/A relative to G/A and G/G was 1.60 (95% CI=1.08-2.36), and the adjusted OR for ALDH2 G/G relative to G/A and A/A was 1.79 (95% CI=1.19-2.69). Significant interactions between ADH2,ALDH2 and drinking were observed. As compared to the subjects with ADH2 G and ALDH2 A alleles, those with ADH2 A/A and ALDH2 G/G genotypes had a significantly increased OR (3.05, 95% CI= 1.67-5.57). The OR for CRC among drinkers with the ,4DH2 A/A genotype was increased to 3.44 (95% CI= 1.84-6.42) compared with non-drinkers with the ADH2 G allele. The OR for CRC among drinkers with theALDH2 G/G genotype was also increased to 2.70 (95% CI= 1.57-4.66) compared with non-drinkers with the ALDH2 A allele.CONCLUSION: Polymorphisms of the ADH2 and ALDH2 genes are significantly associated with CRC risk. There are also significant gene-gene and geneenvironment interactions between drinking and ADH2 and ALDH2 polymorphisms regarding CRC risk in Chinese males.

  9. Aldehyde Dehydrogenase Gene Superfamily in Populus: Organization and Expression Divergence between Paralogous Gene Pairs.

    Directory of Open Access Journals (Sweden)

    Feng-Xia Tian

    Full Text Available Aldehyde dehydrogenases (ALDHs constitute a superfamily of NAD(P+-dependent enzymes that catalyze the irreversible oxidation of a wide range of reactive aldehydes to their corresponding nontoxic carboxylic acids. ALDHs have been studied in many organisms from bacteria to mammals; however, no systematic analyses incorporating genome organization, gene structure, expression profiles, and cis-acting elements have been conducted in the model tree species Populus trichocarpa thus far. In this study, a comprehensive analysis of the Populus ALDH gene superfamily was performed. A total of 26 Populus ALDH genes were found to be distributed across 12 chromosomes. Genomic organization analysis indicated that purifying selection may have played a pivotal role in the retention and maintenance of PtALDH gene families. The exon-intron organizations of PtALDHs were highly conserved within the same family, suggesting that the members of the same family also may have conserved functionalities. Microarray data and qRT-PCR analysis indicated that most PtALDHs had distinct tissue-specific expression patterns. The specificity of cis-acting elements in the promoter regions of the PtALDHs and the divergence of expression patterns between nine paralogous PtALDH gene pairs suggested that gene duplications may have freed the duplicate genes from the functional constraints. The expression levels of some ALDHs were up- or down-regulated by various abiotic stresses, implying that the products of these genes may be involved in the adaptation of Populus to abiotic stresses. Overall, the data obtained from our investigation contribute to a better understanding of the complexity of the Populus ALDH gene superfamily and provide insights into the function and evolution of ALDH gene families in vascular plants.

  10. Aldehyde dehydrogenase 2 in aplastic anemia, Fanconi anemia and hematopoietic stem cells.

    Science.gov (United States)

    Van Wassenhove, Lauren D; Mochly-Rosen, Daria; Weinberg, Kenneth I

    2016-09-01

    Maintenance of the hematopoietic stem cell (HSC) compartment depends on the ability to metabolize exogenously and endogenously generated toxins, and to repair cellular damage caused by such toxins. Reactive aldehydes have been demonstrated to cause specific genotoxic injury, namely DNA interstrand cross-links. Aldehyde dehydrogenase 2 (ALDH2) is a member of a 19 isoenzyme ALDH family with different substrate specificities, subcellular localization, and patterns of expression. ALDH2 is localized in mitochondria and is essential for the metabolism of acetaldehyde, thereby placing it directly downstream of ethanol metabolism. Deficiency in ALDH2 expression and function are caused by a single nucleotide substitution and resulting amino acid change, called ALDH2*2. This genetic polymorphism affects 35-45% of East Asians (about ~560 million people), and causes the well-known Asian flushing syndrome, which results in disulfiram-like reactions after ethanol consumption. Recently, the ALDH2*2 genotype has been found to be associated with marrow failure, with both an increased risk of sporadic aplastic anemia and more rapid progression of Fanconi anemia. This review discusses the unexpected interrelationship between aldehydes, ALDH2 and hematopoietic stem cell biology, and in particular its relationship to Fanconi anemia. PMID:27650066

  11. Reversible, partial inactivation of plant betaine aldehyde dehydrogenase by betaine aldehyde: mechanism and possible physiological implications.

    Science.gov (United States)

    Zárate-Romero, Andrés; Murillo-Melo, Darío S; Mújica-Jiménez, Carlos; Montiel, Carmina; Muñoz-Clares, Rosario A

    2016-04-01

    In plants, the last step in the biosynthesis of the osmoprotectant glycine betaine (GB) is the NAD(+)-dependent oxidation of betaine aldehyde (BAL) catalysed by some aldehyde dehydrogenase (ALDH) 10 enzymes that exhibit betaine aldehyde dehydrogenase (BADH) activity. Given the irreversibility of the reaction, the short-term regulation of these enzymes is of great physiological relevance to avoid adverse decreases in the NAD(+):NADH ratio. In the present study, we report that the Spinacia oleracea BADH (SoBADH) is reversibly and partially inactivated by BAL in the absence of NAD(+)in a time- and concentration-dependent mode. Crystallographic evidence indicates that the non-essential Cys(450)(SoBADH numbering) forms a thiohemiacetal with BAL, totally blocking the productive binding of the aldehyde. It is of interest that, in contrast to Cys(450), the catalytic cysteine (Cys(291)) did not react with BAL in the absence of NAD(+) The trimethylammonium group of BAL binds in the same position in the inactivating or productive modes. Accordingly, BAL does not inactivate the C(450)SSoBADH mutant and the degree of inactivation of the A(441)I and A(441)C mutants corresponds to their very different abilities to bind the trimethylammonium group. Cys(450)and the neighbouring residues that participate in stabilizing the thiohemiacetal are strictly conserved in plant ALDH10 enzymes with proven or predicted BADH activity, suggesting that inactivation by BAL is their common feature. Under osmotic stress conditions, this novel partial and reversible covalent regulatory mechanism may contribute to preventing NAD(+)exhaustion, while still permitting the synthesis of high amounts of GB and avoiding the accumulation of the toxic BAL.

  12. Situational aldehyde dehydrogenase expression by regulatory T cells may explain the contextual duality of cyclophosphamide as both a pro-inflammatory and tolerogenic agent

    OpenAIRE

    Kanakry, Christopher G.; Ganguly, Sudipto; Luznik, Leo

    2015-01-01

    In two recent publications, we demonstrated that after allogeneic stimulation, regulatory T cells (Tregs) increase expression of aldehyde dehydrogenase (ALDH), the major in vivo mechanism of cyclophosphamide detoxification, thereby becoming cyclophosphamide resistant. Differential ALDH expression may explain why cyclophosphamide has pro- and anti-inflammatory effects that are temporally and contextually dependent.

  13. Characterization of aldehyde dehydrogenase isozymes in ovarian cancer tissues and sphere cultures

    International Nuclear Information System (INIS)

    Aldehyde dehydrogenases belong to a superfamily of detoxifying enzymes that protect cells from carcinogenic aldehydes. Of the superfamily, ALDH1A1 has gained most attention because current studies have shown that its expression is associated with human cancer stem cells. However, ALDH1A1 is only one of the 19 human ALDH subfamilies currently known. The purpose of the present study was to determine if the expression and activities of other major ALDH isozymes are associated with human ovarian cancer and ovarian cancer sphere cultures. Immunohistochemistry was used to delineate ALDH isozyme localization in clinical ovarian tissues. Western Blot analyses were performed on lysates prepared from cancer cell lines and ovarian cancer spheres to confirm the immunohistochemistry findings. Quantitative reverse transcription-polymerase chain reactions were used to measure the mRNA expression levels. The Aldefluor® assay was used to measure ALDH activity in cancer cells from the four tumor subtypes. Immunohistochemical staining showed significant overexpression of ALDH1A3, ALDH3A2, and ALDH7A1 isozymes in ovarian tumors relative to normal ovarian tissues. The expression and activity of ALDH1A1 is tumor type-dependent, as seen from immunohistochemisty, Western blot analysis, and the Aldefluor® assay. The expression was elevated in the mucinous and endometrioid ovarian epithelial tumors than in serous and clear cell tumors. In some serous and most clear cell tumors, ALDH1A1 expression was found in the stromal fibroblasts. RNA expression of all studied ALDH isozymes also showed higher expression in endometrioid and mucinous tumors than in the serous and clear cell subtypes. The expression of ALDH enzymes showed tumor type-dependent induction in ovarian cancer cells growing as sphere suspensions in serum-free medium. The results of our study indicate that ALDH enzyme expression and activity may be associated with specific cell types in ovarian tumor tissues and vary according to

  14. Residues that influence coenzyme preference in the aldehyde dehydrogenases.

    Science.gov (United States)

    González-Segura, Lilian; Riveros-Rosas, Héctor; Julián-Sánchez, Adriana; Muñoz-Clares, Rosario A

    2015-06-01

    To find out the residues that influence the coenzyme preference of aldehyde dehydrogenases (ALDHs), we reviewed, analyzed and correlated data from their known crystal structures and amino-acid sequences with their published kinetic parameters for NAD(P)(+). We found that the conformation of the Rossmann-fold loops participating in binding the adenosine ribose is very conserved among ALDHs, so that coenzyme specificity is mainly determined by the nature of the residue at position 195 (human ALDH2 numbering). Enzymes with glutamate or proline at 195 prefer NAD(+) because the side-chains of these residues electrostatically and/or sterically repel the 2'-phosphate group of NADP(+). But contrary to the conformational rigidity of proline, the conformational flexibility of glutamate may allow NADP(+)-binding in some enzymes by moving the carboxyl group away from the 2'-phosphate group, which is possible if a small neutral residue is located at position 224, and favored if the residue at position 53 interacts with Glu195 in a NADP(+)-compatible conformation. Of the residues found at position 195, only glutamate interacts with the NAD(+)-adenosine ribose; glutamine and histidine cannot since their side-chain points are opposite to the ribose, probably because the absence of the electrostatic attraction by the conserved nearby Lys192, or its electrostatic repulsion, respectively. The shorter side-chains of other residues-aspartate, serine, threonine, alanine, valine, leucine, or isoleucine-are distant from the ribose but leave room for binding the 2'-phosphate group. Generally, enzymes having a residue different from Glu bind NAD(+) with less affinity, but they can also bind NADP(+) even sometimes with higher affinity than NAD(+), as do enzymes containing Thr/Ser/Gln195. Coenzyme preference is a variable feature within many ALDH families, consistent with being mainly dependent on a single residue that apparently has no other structural or functional roles, and therefore can

  15. Immunohistochemical analysis of aldehyde dehydrogenase isoforms and their association with estrogen-receptor status and disease progression in breast cancer

    Science.gov (United States)

    Opdenaker, Lynn M; Arnold, Kimberly M; Pohlig, Ryan T; Padmanabhan, Jayasree S; Flynn, Daniel C; Sims-Mourtada, Jennifer

    2014-01-01

    In many types of tumors, especially breast tumors, aldehyde dehydrogenase (ALDH) activity has been used to identify cancer stem-like cells within the tumor. The presence and quantity of these cells are believed to predict the response of tumors to chemotherapy. Therefore, identification and eradication of these cells would be necessary to cure the patient. However, there are 19 different ALDH isoforms that could contribute to the enzyme activity. ALDH1A1 and ALDH1A3 are among the isoforms mostly responsible for the increased ALDH activity observed in these stem-like cells, although the main isoforms vary in different tissues and tumor types. In the study reported here, we attempted to determine if ALDH1A1 or ALDH1A3, specifically, correlate with tumor stage, grade, and hormone-receptor status in breast-cancer patients. While there was no significant correlation between ALDH1A1 and any of the parameters tested, we were able to identify a positive correlation between ALDH1A3 and tumor stage in triple-negative cancers. In addition, ALDH1A3 was negatively correlated with estrogen-receptor status. Our data suggest that ALDH1A3 could be utilized as a marker to identify stem-like cells within triple-negative tumors. PMID:25540596

  16. Aldehyde dehydrogenase-derived omega-crystallins of squid and octopus. Specialization for lens expression.

    Science.gov (United States)

    Zinovieva, R D; Tomarev, S I; Piatigorsky, J

    1993-05-25

    omega-Crystallin of the octopus lens is related to aldehyde dehydrogenases (ALDH) of vertebrates (Tomarev, S. I., Zinovieva, R. D., and Piatigorsky, J. (1991) J. Biol. Chem. 266, 24226-24231) and ALDH1/eta-crystallin of elephant shrews (Wistow, G., and Kim, H. (1991) J. Mol. Evol. 32, 262-269). Only very low amounts of omega-crystallin are present in the squid lens. Here, we have cloned omega-crystallin cDNAs of the octopus (Octopus dofleini) and squid (Ommastrephes sloani pacificus) lenses. The deduced amino acid sequences of omega-crystallin from these species are 78% identical to each other, 56-58% identical to cytoplasmic ALDH1 and mitochondrial ALDH2 of vertebrates (which are 66-68% identical to each other), and 40% identical to Escherichia coli and spinach ALDHs. These data are consistent with the idea that the ALDH1/ALDH2 gene duplication in vertebrates occurred after divergence of cephalopods from the line giving rise to vertebrates, but before the separation of squid and octopus. Southern blot hybridization indicated that omega-crystallin is encoded by few genes (possibly just one) in octopus and squid. Northern blot hybridization revealed two bands (2.7 and 9.0 kilobases) of omega-crystallin RNA in the octopus lens and one band (4.2 kilobases) in the squid lens; omega-crystallin RNAs were undetectable in numerous non-lens tissues of octopus and squid, suggesting lens-specific expression of this gene(s). Finally, extracts of the octopus lens had no detectable ALDH activity using different substrates, consistent with omega-crystallin having no enzymatic activity. Taken together, our results suggest that omega-crystallin evolved by duplication of an ancestral gene encoding ALDH and subsequently specialized for refraction in the transparent lens while losing ALDH activity and expression in other tissues. PMID:7684383

  17. Aldehyde Dehydrogenase 1 Is a Tumor Stem Cell-Associated Marker in Lung Cancer

    OpenAIRE

    Jiang, Feng; Qiu, Qi; Khanna, Abha; Todd, Nevins W.; Deepak, Janaki; Xing, Lingxiao; Wang, Huijun; Liu, Zhenqiu; Su, Yun; Stass, Sanford A.; Katz, Ruth L

    2009-01-01

    Tumor contains small population of cancer stem cells (CSC) that are responsible for its maintenance and relapse. Analysis of these CSCs may lead to effective prognostic and therapeutic strategies for the treatment of cancer patients. We report here the identification of CSCs from human lung cancer cells using Aldefluor assay followed by fluorescence-activated cell sorting analysis. Isolated cancer cells with relatively high aldehyde dehydrogenase 1 (ALDH1) activity display in vitro features o...

  18. Amino Acid Residues Critical for the Specificity for Betaine Aldehyde of the Plant ALDH10 Isoenzyme Involved in the Synthesis of Glycine Betaine1[W][OA

    Science.gov (United States)

    Díaz-Sánchez, Ángel G.; González-Segura, Lilian; Mújica-Jiménez, Carlos; Rudiño-Piñera, Enrique; Montiel, Carmina; Martínez-Castilla, León P.; Muñoz-Clares, Rosario A.

    2012-01-01

    Plant Aldehyde Dehydrogenase10 (ALDH10) enzymes catalyze the oxidation of ω-primary or ω-quaternary aminoaldehydes, but, intriguingly, only some of them, such as the spinach (Spinacia oleracea) betaine aldehyde dehydrogenase (SoBADH), efficiently oxidize betaine aldehyde (BAL) forming the osmoprotectant glycine betaine (GB), which confers tolerance to osmotic stress. The crystal structure of SoBADH reported here shows tyrosine (Tyr)-160, tryptophan (Trp)-167, Trp-285, and Trp-456 in an arrangement suitable for cation-π interactions with the trimethylammonium group of BAL. Mutation of these residues to alanine (Ala) resulted in significant Km(BAL) increases and Vmax/Km(BAL) decreases, particularly in the Y160A mutant. Tyr-160 and Trp-456, strictly conserved in plant ALDH10s, form a pocket where the bulky trimethylammonium group binds. This space is reduced in ALDH10s with low BADH activity, because an isoleucine (Ile) pushes the Trp against the Tyr. Those with high BADH activity instead have Ala (Ala-441 in SoBADH) or cysteine, which allow enough room for binding of BAL. Accordingly, the mutation A441I decreased the Vmax/Km(BAL) of SoBADH approximately 200 times, while the mutation A441C had no effect. The kinetics with other ω-aminoaldehydes were not affected in the A441I or A441C mutant, demonstrating that the existence of an Ile in the second sphere of interaction of the aldehyde is critical for discriminating against BAL in some plant ALDH10s. A survey of the known sequences indicates that plants have two ALDH10 isoenzymes: those known to be GB accumulators have a high-BAL-affinity isoenzyme with Ala or cysteine in this critical position, while non GB accumulators have low-BAL-affinity isoenzymes containing Ile. Therefore, BADH activity appears to restrict GB synthesis in non-GB-accumulator plants. PMID:22345508

  19. Immunohistochemical analysis of aldehyde dehydrogenase isoforms and their association with estrogen-receptor status and disease progression in breast cancer

    Directory of Open Access Journals (Sweden)

    Opdenaker LM

    2014-12-01

    Full Text Available Lynn M Opdenaker,1,2 Kimberly M Arnold,1,3 Ryan T Pohlig,3,4 Jayasree S Padmanabhan,1 Daniel C Flynn,1,3 Jennifer Sims-Mourtada1–3 1Center for Translational Cancer Research, Helen F Graham Cancer Center, Christiana Care Health Services, Inc., Newark, Delaware, USA; 2Department of Biological Sciences, 3Department of Medical Laboratory Sciences, 4Biostatistics Core Facility, University of Delaware, Newark, Delaware, USA Abstract: In many types of tumors, especially breast tumors, aldehyde dehydrogenase (ALDH activity has been used to identify cancer stem-like cells within the tumor. The presence and quantity of these cells are believed to predict the response of tumors to chemotherapy. Therefore, identification and eradication of these cells would be necessary to cure the patient. However, there are 19 different ALDH isoforms that could contribute to the enzyme activity. ALDH1A1 and ALDH1A3 are among the isoforms mostly responsible for the increased ALDH activity observed in these stem-like cells, although the main isoforms vary in different tissues and tumor types. In the study reported here, we attempted to determine if ALDH1A1 or ALDH1A3, specifically, correlate with tumor stage, grade, and hormone-receptor status in breast-cancer patients. While there was no significant correlation between ALDH1A1 and any of the parameters tested, we were able to identify a positive correlation between ALDH1A3 and tumor stage in triple-negative cancers. In addition, ALDH1A3 was negatively correlated with estrogen-receptor status. Our data suggest that ALDH1A3 could be utilized as a marker to identify stem-like cells within triple-negative tumors. Keywords: breast tumor, ALDH, ALDH1A1, ALDH1A3, stem-like cells, triple-negative cancer

  20. Potent inhibition of aldehyde dehydrogenase-2 by diphenyleneiodonium: focus on nitroglycerin bioactivation.

    Science.gov (United States)

    Neubauer, Regina; Neubauer, Andrea; Wölkart, Gerald; Schwarzenegger, Christine; Lang, Barbara; Schmidt, Kurt; Russwurm, Michael; Koesling, Doris; Gorren, Antonius C F; Schrammel, Astrid; Mayer, Bernd

    2013-09-01

    Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN) to yield nitric oxide (NO) or a related species that activates soluble guanylate cyclase (sGC), resulting in cGMP-mediated vasodilation. Accordingly, established ALDH2 inhibitors attenuate GTN-induced vasorelaxation in vitro and in vivo. However, the ALDH2 hypothesis has not been reconciled with early studies demonstrating potent inhibition of the GTN response by diphenyleneiodonium (DPI), a widely used inhibitor of flavoproteins, in particular NADPH oxidases. We addressed this issue and investigated the effects of DPI on GTN-induced relaxation of rat aortic rings and the function of purified ALDH2. DPI (0.3 µM) inhibited the high affinity component of aortic relaxation to GTN without affecting the response to NO, indicating that the drug interfered with GTN bioactivation. Denitration and bioactivation of 1-2 µM GTN, assayed as 1,2-glycerol dinitrate formation and activation of purified sGC, respectively, were inhibited by DPI with a half-maximally active concentration of about 0.2 µM in a GTN-competitive manner. Molecular modeling indicated that DPI binds to the catalytic site of ALDH2, and this was confirmed by experiments showing substrate-competitive inhibition of the dehydrogenase and esterase activities of the enzyme. Our data identify ALDH2 as highly sensitive target of DPI and explain inhibition of GTN-induced relaxation by this drug observed previously. In addition, the data provide new evidence for the essential role of ALDH2 in GTN bioactivation and may have implications to other fields of ALDH2 research, such as hepatic ethanol metabolism and cardiac ischemia/reperfusion injury.

  1. Aldehyde dehydrogenase-independent bioactivation of nitroglycerin in porcine and bovine blood vessels.

    Science.gov (United States)

    Neubauer, Regina; Wölkart, Gerald; Opelt, Marissa; Schwarzenegger, Christine; Hofinger, Marielies; Neubauer, Andrea; Kollau, Alexander; Schmidt, Kurt; Schrammel, Astrid; Mayer, Bernd

    2015-02-15

    The vascular bioactivation of the antianginal drug nitroglycerin (GTN), yielding 1,2-glycerol dinitrate and nitric oxide or a related activator of soluble guanylate cyclase, is catalyzed by aldehyde dehydrogenase-2 (ALDH2) in rodent and human blood vessels. The essential role of ALDH2 has been confirmed in many studies and is considered as general principle of GTN-induced vasodilation in mammals. However, this view is challenged by an early report showing that diphenyleneiodonium, which we recently characterized as potent ALDH2 inhibitor, has no effect on GTN-induced relaxation of bovine coronary arteries (De La Lande et al., 1996). We investigated this issue and found that inhibition of ALDH2 attenuates GTN-induced coronary vasodilation in isolated perfused rat hearts but has no effect on relaxation to GTN of bovine and porcine coronary arteries. This observation is explained by low levels of ALDH2 protein expression in bovine coronary arteries and several types of porcine blood vessels. ALDH2 mRNA expression and the rates of GTN denitration were similarly low, excluding a significant contribution of ALDH2 to the bioactivation of GTN in these vessels. Attempts to identify the responsible pathway with enzyme inhibitors did not provide conclusive evidence for the involvement of ALDH3A1, cytochrome P450, or GSH-S-transferase. Thus, the present manuscript describes a hitherto unrecognized pathway of GTN bioactivation in bovine and porcine blood vessels. If present in the human vasculature, this pathway might contribute to the therapeutic effects of organic nitrates that are not metabolized by ALDH2.

  2. Aldehyde dehydrogenase 2 is associated with cognitive functions in patients with Parkinson’s disease

    Science.gov (United States)

    Yu, Rwei-Ling; Tan, Chun-Hsiang; Lu, Ying-Che; Wu, Ruey-Meei

    2016-01-01

    Neurotransmitter degradation has been proposed to cause the accumulation of neurotoxic metabolites. The metabolism of these metabolites involves aldehyde dehydrogenase 2 (ALDH2). The Asian-specific single nucleotide polymorphism rs671 causes reduced enzyme activity. This study aims to explore whether Parkinson’s disease (PD) patients with reduced ALDH2 activity owing to the rs671 polymorphism are at risk for neuropsychological impairments. A total of 139 PD patients were recruited. Each participant was assessed for medical characteristics and their ALDH2 genotype. The Mini-Mental State Examination (MMSE), the Clinical Dementia Rating Scale and the Frontal Behavioral Inventory were used to measure neuropsychological functions. We found that the MMSE scores were significantly lower in patients with inactive ALDH2 (U = 1873.5, p = 0.02). The presence of cognitive impairments was significantly more frequent in the inactive ALDH2 group (46.0%) than in the active ALDH2 group (26.3%) (χ2 = 5.886, p = 0.01). The inactive group showed significant deterioration in hobbies and exhibited more severe “disorganization” and “hyper-sexuality” behaviours. The additive effects of the allele on the development of cognitive impairments in PD patients may be an important finding that provides further insight into the pathogenic mechanism of cognitive dysfunction in PD. PMID:27453488

  3. Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer

    Directory of Open Access Journals (Sweden)

    Mieog J Sven D

    2012-01-01

    Full Text Available Abstract Background The purpose of this study was to compare the expression and the prognostic effect of the breast cancer stem cell marker aldehyde dehydrogenase-1 (ALDH1 in young and elderly breast cancer patients. Methods The study population (N = 574 consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Median follow-up was 17.9 years (range: 0.1 to 23.5. Tissue microarray slides were immunohistochemically stained for ALDH1 expression and quantified by two independent observers who were blinded to clinical outcome. Assessment of the prognostic effect of ALDH1 expression was stratified according to age and systemic treatment. Results Complete lack of expression of ALDH1 was found in 40% of tumors. With increasing age more tumors showed complete absence of ALDH1 expression (P 65 years, ALDH1 status was not associated with any clinical outcome. Conversely, in patients aged P = .021 and relative survival (relative excess risks of death = 2.36 (95% CI, 1.22 to 3.68; P = .016. Ten-year relative survival risk was 57% in ALDH1-positive patients compared to 83% in ALDH1-negative patients. Conclusion ALDH1 expression and its prognostic effect are age-dependent. Our results support the hypothesis that breast cancer biology is different in elderly patients compared to their younger counterparts and emphasizes the importance of taking into consideration age-specific interactions in breast cancer research.

  4. Characterization of Cardiac-Resident Progenitor Cells Expressing High Aldehyde Dehydrogenase Activity

    Directory of Open Access Journals (Sweden)

    Marc-Estienne Roehrich

    2013-01-01

    Full Text Available High aldehyde dehydrogenase (ALDH activity has been associated with stem and progenitor cells in various tissues. Human cord blood and bone marrow ALDH-bright (ALDHbr cells have displayed angiogenic activity in preclinical studies and have been shown to be safe in clinical trials in patients with ischemic cardiovascular disease. The presence of ALDHbr cells in the heart has not been evaluated so far. We have characterized ALDHbr cells isolated from mouse hearts. One percent of nonmyocytic cells from neonatal and adult hearts were ALDHbr. ALDHvery-br cells were more frequent in neonatal hearts than adult. ALDHbr cells were more frequent in atria than ventricles. Expression of ALDH1A1 isozyme transcripts was highest in ALDHvery-br cells, intermediate in ALDHbr cells, and lowest in ALDHdim cells. ALDH1A2 expression was highest in ALDHvery-br cells, intermediate in ALDHdim cells, and lowest in ALDHbr cells. ALDH1A3 and ALDH2 expression was detectable in ALDHvery-br and ALDHbr cells, unlike ALDHdim cells, albeit at lower levels compared with ALDH1A1 and ALDH1A2. Freshly isolated ALDHbr cells were enriched for cells expressing stem cell antigen-1, CD34, CD90, CD44, and CD106. ALDHbr cells, unlike ALDHdim cells, could be grown in culture for more than 40 passages. They expressed sarcomeric α-actinin and could be differentiated along multiple mesenchymal lineages. However, the proportion of ALDHbr cells declined with cell passage. In conclusion, the cardiac-derived ALDHbr population is enriched for progenitor cells that exhibit mesenchymal progenitor-like characteristics and can be expanded in culture. The regenerative potential of cardiac-derived ALDHbr cells remains to be evaluated.

  5. Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury by inhibiting aldehyde dehydrogenase 2 activity in rats%急性高血糖通过抑制 ALDH2活性加重大鼠心肌缺血/再灌注损伤

    Institute of Scientific and Technical Information of China (English)

    李明华; 王甲莉; 徐峰; 袁秋环; 刘宝山; 庞佼佼; 张运; 陈玉国

    2015-01-01

    及心肌细胞凋亡。%Objective To investigate the activity changes and actions of aldehyde dehydrogenase 2 (ALDH2)in myocardial ischemia/reperfusion injury exacerbated by acute hyperglycemia.Methods A total of 48 male Wistar rats were randomly divided into 4 groups:sham operation (SHAM)group,normal saline control (CON)group,high blood glucose (HG)group,and HG with Alda-1 administration (HG +Alda-1)group,with 12 animals in each group. The left anterior descending artery (LAD)was occluded for 30 minutes followed by 1 hour reperfusion to establish my-ocardial ischemia-reperfusion rat models.Acute hyperglycemia rat models were established via jugular vein injection of 50% glucose (3 g /kg)during the ischemia period.Blood glucose levels were maintained at 20-28 mmol/L throughout the experiment by administration of glucose with trace pumping[4 mL/(kg·h)]during ischemia and reperfusion peri-od.The rats in CON group and HG +Alda-1 group were given normal saline (6 mL/kg).The rats in HG +Alda-1 group were given Alda-1 (8.5 mg /kg)with trace pumping during ischemia and reperfusion.After reperfusion,ALDH2 activity of heart was detected with colorimetric method,changes of myocardial tissue morphology were observed with HE staining,myocardial infarction size was determined with TTC staining,and myocardial cell apoptosis was tested with TUNEL method.Results Blood glucose level was significantly increased in HG group compared with that of CON group [(23.4 ±0.21 )vs (5.8 ±0.21 )mmol/L,P <0.01 ].Compared with CON group,the activity of ALDH2 in HG group was markedly decreased [(69.1 ±5.16)% vs (87.0 ±4.30)%,P <0.05].Myocardial infarct size of HG group was remarkably increased compared with the CON group [(38.2 ±3.30)% vs (26.8 ±2.53)%, P <0.05].Compared with HG group,myocardial infarct size of HG +Alda-1 group was notedly decreased [(27.8 ± 2.50)% vs (38.2 ±3.30)%,P <0.05].Myocardial apoptosis index of HG group was significantly higher than that of CON group [(16.1 ±0.83)% vs (13.1 ±0.39)%,P <0

  6. 急性高血糖通过抑制 ALDH2活性加重大鼠心肌缺血/再灌注损伤%Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury by inhibiting aldehyde dehydrogenase 2 activity in rats

    Institute of Scientific and Technical Information of China (English)

    李明华; 王甲莉; 徐峰; 袁秋环; 刘宝山; 庞佼佼; 张运; 陈玉国

    2015-01-01

    Objective To investigate the activity changes and actions of aldehyde dehydrogenase 2 (ALDH2)in myocardial ischemia/reperfusion injury exacerbated by acute hyperglycemia.Methods A total of 48 male Wistar rats were randomly divided into 4 groups:sham operation (SHAM)group,normal saline control (CON)group,high blood glucose (HG)group,and HG with Alda-1 administration (HG +Alda-1)group,with 12 animals in each group. The left anterior descending artery (LAD)was occluded for 30 minutes followed by 1 hour reperfusion to establish my-ocardial ischemia-reperfusion rat models.Acute hyperglycemia rat models were established via jugular vein injection of 50% glucose (3 g /kg)during the ischemia period.Blood glucose levels were maintained at 20-28 mmol/L throughout the experiment by administration of glucose with trace pumping[4 mL/(kg·h)]during ischemia and reperfusion peri-od.The rats in CON group and HG +Alda-1 group were given normal saline (6 mL/kg).The rats in HG +Alda-1 group were given Alda-1 (8.5 mg /kg)with trace pumping during ischemia and reperfusion.After reperfusion,ALDH2 activity of heart was detected with colorimetric method,changes of myocardial tissue morphology were observed with HE staining,myocardial infarction size was determined with TTC staining,and myocardial cell apoptosis was tested with TUNEL method.Results Blood glucose level was significantly increased in HG group compared with that of CON group [(23.4 ±0.21 )vs (5.8 ±0.21 )mmol/L,P <0.01 ].Compared with CON group,the activity of ALDH2 in HG group was markedly decreased [(69.1 ±5.16)% vs (87.0 ±4.30)%,P <0.05].Myocardial infarct size of HG group was remarkably increased compared with the CON group [(38.2 ±3.30)% vs (26.8 ±2.53)%, P <0.05].Compared with HG group,myocardial infarct size of HG +Alda-1 group was notedly decreased [(27.8 ± 2.50)% vs (38.2 ±3.30)%,P <0.05].Myocardial apoptosis index of HG group was significantly higher than that of CON group [(16.1 ±0.83)% vs (13.1 ±0.39)%,P

  7. Mesenchymal Stem/Stromal Cells Derived From a Reproductive Tissue Niche Under Oxidative Stress Have High Aldehyde Dehydrogenase Activity.

    Science.gov (United States)

    Kusuma, Gina D; Abumaree, Mohamed H; Pertile, Mark D; Perkins, Anthony V; Brennecke, Shaun P; Kalionis, Bill

    2016-06-01

    The use of mesenchymal stem/stromal cells (MSC) in regenerative medicine often requires MSC to function in environments of high oxidative stress. Human pregnancy is a condition where the mother's tissues, and in particular her circulatory system, are exposed to increased levels of oxidative stress. MSC in the maternal decidua basalis (DMSC) are in a vascular niche, and thus would be exposed to oxidative stress products in the maternal circulation. Aldehyde dehydrogenases (ALDH) are a large family of enzymes which detoxify aldehydes and thereby protect stem cells against oxidative damage. A subpopulation of MSC express high levels of ALDH (ALDH(br)) and these are more potent in repairing and regenerating tissues. DMSC was compared with chorionic villous MSC (CMSC) derived from the human placenta. CMSC reside in vascular niche and are exposed to the fetal circulation, which is in lower oxidative state. We screened an ALDH isozyme cDNA array and determined that relative to CMSC, DMSC expressed high levels of ALDH1 family members, predominantly ALDH1A1. Immunocytochemistry gave qualitative confirmation at the protein level. Immunofluorescence detected ALDH1 immunoreactivity in the DMSC and CMSC vascular niche. The percentage of ALDH(br) cells was calculated by Aldefluor assay and DMSC showed a significantly higher percentage of ALDH(br) cells than CMSC. Finally, flow sorted ALDH(br) cells were functionally potent in colony forming unit assays. DMSC, which are derived from pregnancy tissues that are naturally exposed to high levels of oxidative stress, may be better candidates for regenerative therapies where MSC must function in high oxidative stress environments. PMID:26880140

  8. Aldehyde dehydrogenase 1A1 stabilizes transcription factor Gli2 and enhances the activity of Hedgehog signaling in hepatocellular cancer.

    Science.gov (United States)

    Yan, Zhengwei; Xu, Liyao; Zhang, Junyan; Lu, Quqin; Luo, Shiwen; Xu, Linlin

    2016-03-18

    The Gli transcription factors are primary transcriptional regulators that mediate the activation of Hedgehog (Hh) signaling. Recent studies have revealed that Gli proteins are also regulated transcriptionally and post-translationally through noncanonical mechanisms, independent of Hh signaling. However, the precise mechanisms involved in the regulation of Gli proteins remain unclear. Using a differential mass-spectrometry approach, we found that aldehyde dehydrogenase 1A1 (ALDH1A1) is associated with transcription factor Gli2. Overexpression of ALDH1A1 increased Gli2 protein levels; in contrast, ALDH1A1 depletion facilitated Gli2 degradation. In addition, Gli2 mRNA expression was not affected by ectopic expression of ALDH1A1, indicating the role of ALDH1A1 in the stabilization of Gli2. Further investigation showed that ALDH1A1 prolonged the stability of Gli2 protein in a catalytic-independent manner. Finally, we showed that overexpression of ALDH1A1 activated the Hh signaling pathway and promoted cell growth, migration and invasion in hepatocellular cancer cells. Together, these results illustrate regulatory roles of ALDH1A1 in the activation of the Hh signaling pathway and highlight a novel mechanism for the aberrant activation of the Hh signaling pathway in hepatocellular cancer cells. PMID:26896768

  9. Effect of various chemicals on the aldehyde dehydrogenase activity of the rat liver cytosol.

    Science.gov (United States)

    Marselos, M; Vasiliou, V

    1991-01-01

    The cytosolic activity of aldehyde dehydrogenase (ALDH) was studied in the rat liver, after acute administration of various carcinogenic and chemically related compounds. Male Wistar rats were treated with 27 different chemicals, including polycyclic aromatic hydrocarbons, aromatic amines, nitrosamines, azo dyes, as well as with some known direct-acting carcinogens. The cytosolic ALDH activity of the liver was determined either with propionaldehyde and NAD (P/NAD), or with benzaldehyde and NADP (B/NADP). The activity of ALDH remained unaffected after treatment with 1-naphthylamine, nitrosamines and also with the direct-acting chemical carcinogens tested. On the contrary, polycyclic aromatic hydrocarbons, polychlorinated biphenyls (Arochlor 1254) and 2-naphthylamine produced a remarkable increase of ALDH. In general, the response to the effectors was disproportionate between the two types of enzyme activity, being much in favour for the B/NADP activity. This fact resulted to an inversion of the ratio B/NADP vs. P/NAD, which under constitutive conditions is lower than 1. In this respect, the most potent compounds were found to be polychlorinated biphenyls, 3-methylcholanthrene, benzo(a)pyrene and 1,2,5,6-dibenzoanthracene. Our results suggest that the B/NADP activity of the soluble ALDH is greatly induced after treatment with compounds possessing aromatic ring(s) in their molecule. It is not known, if this response of the hepatocytes is related with the process of chemical carcinogenesis. PMID:2060039

  10. Correlations Between Polymorphisms of Extracellular Superoxide Dismutase, Aldehyde Dehydrogenase-2 Genes, as Well as Drinking Behavior and Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    Chao-xian Zhang; Yong-mei Qin; Li-ke Guo

    2014-01-01

    Objective To investigate the correlation between drinking behavior combined with polymorphisms of extracellular superoxide dismutase (EC-SOD) and aldehyde dehydrogenase-2 (ALDH2) genes and pancreatic cancer. Methods The genetic polymorphisms of EC-SOD and ALDH2 were analyzed by polymerase chain reaction restriction fragment length polymorphism in the peripheral blood leukocytes obtained from 680 pancreatic cancer cases and 680 non-cancer controls. Subsequently the frequency of genotype was compared between the pancreatic cancer patients and the healthy controls.The relationship of drinking with pancreatic cancer was analyzed. Results The frequencies of EC-SOD (C/G) and ALDH2 variant genotypes were 37.35% and 68.82%respectively in the pancreatic cancer cases, and were significantly higher than those in the healthy controls (21.03% and 44.56%, all P Conclusion EC-SOD (C/G), ALDH2 variant genotypes and drinking might be the risk factors of pancreatic cancer.

  11. Aldehyde Dehydrogenase1 Immunohistochemical Staining in Primary Breast Cancer Cells Independently Predicted Overall Survival But Did Not Correlate with the Presence of Circulating or Disseminated Tumors Cells

    OpenAIRE

    Woodward, Wendy A.; Krishnamurthy, Savitri; Lodhi, Ashutosh; Xiao, Lianchun; Gong, Yun; Cristofanilli, Massimo; Buchholz, Thomas A.; Lucci, Anthony

    2014-01-01

    Purpose: We hypothesized that aldehyde dehydrogenase 1 (ALDH1) staining in breast cancer tumor cells might be a simple surrogate for the presence of circulating tumor cells (CTCs) or disseminated tumor cells (DTCs). Experimental Design: Whole tissue primary tumor sections from 121 patients enrolled in a clinical trial assessing CTCs and DTCs at the time of surgery were stained for ALDH1 and scored by a dedicated breast pathologist blinded to outcome. Clinical data was extracted and staining w...

  12. Surviving environmental stress: the role of betaine aldehyde dehydrogenase in marine crustaceans

    Directory of Open Access Journals (Sweden)

    NA Stephens-Camacho

    2015-02-01

    Full Text Available Betaine aldehyde dehydrogenase (BADH belongs to the aldehyde dehydrogenases (ALDH family, an ancestral group of enzymes responsible for aldehyde detoxification in several organisms. The BADH enzyme catalyzes the irreversible oxidation of betaine aldehyde to glycine betaine (GB an important osmoptrotector and osmoregulator accumulated in response to cellular osmotic stress. The BADH enzymes have been extensively described in terrestrial organisms, but information in marine crustaceans remains scarce. Research on crustacean stress-adaptive capacity to environmental stressors relates GB accumulation in response to salinity variations. Although GB de novo synthesis is confirmed on crustaceans, its metabolic pathways and regulation mechanism are unexplored. In this work, the state of the knowledge of betaine aldehyde dehydrogenase enzymes in marine crustaceans is summarized, as a mechanism to overcome the deleterious effects of changes in temperature, salinity and dissolved oxygen concentration in seawater. The purpose of this review is to provide a more comprehensive overview to set the basis for exploring novel functions and properties of BADHs on the response of crustaceans to environmental stress.

  13. Glu504Lys Single Nucleotide Polymorphism of Aldehyde Dehydrogenase 2 Gene and the Risk of Human Diseases

    Directory of Open Access Journals (Sweden)

    Yan Zhao

    2015-01-01

    Full Text Available Aldehyde dehydrogenase (ALDH 2 is a mitochondrial enzyme that is known for its important role in oxidation and detoxification of ethanol metabolite acetaldehyde. ALDH2 also metabolizes other reactive aldehydes such as 4-hydroxy-2-nonenal and acrolein. The Glu504Lys single nucleotide polymorphism (SNP of ALDH2 gene, which is found in approximately 40% of the East Asian populations, causes defect in the enzyme activity of ALDH2, leading to alterations in acetaldehyde metabolism and alcohol-induced “flushing” syndrome. Evidence suggests that ALDH2 Glu504Lys SNP is a potential candidate genetic risk factor for a variety of chronic diseases such as cardiovascular disease, cancer, and late-onset Alzheimer’s disease. In addition, the association between ALDH2 Glu504Lys SNP and the development of these chronic diseases appears to be affected by the interaction between the SNP and lifestyle factors such as alcohol consumption as well as by the presence of other genetic variations.

  14. Autocrine function of aldehyde dehydrogenase 1 as a determinant of diet- and sex-specific differences in visceral adiposity.

    Science.gov (United States)

    Yasmeen, Rumana; Reichert, Barbara; Deiuliis, Jeffrey; Yang, Fangping; Lynch, Alisha; Meyers, Joseph; Sharlach, Molly; Shin, Sangsu; Volz, Katharina S; Green, Kari B; Lee, Kichoon; Alder, Hansjuerg; Duester, Gregg; Zechner, Rudolf; Rajagopalan, Sanjay; Ziouzenkova, Ouliana

    2013-01-01

    Mechanisms for sex- and depot-specific fat formation are unclear. We investigated the role of retinoic acid (RA) production by aldehyde dehydrogenase 1 (Aldh1a1, -a2, and -a3), the major RA-producing enzymes, on sex-specific fat depot formation. Female Aldh1a1(-/-) mice, but not males, were resistant to high-fat (HF) diet-induced visceral adipose formation, whereas subcutaneous fat was reduced similarly in both groups. Sexual dimorphism in visceral fat (VF) was attributable to elevated adipose triglyceride lipase (Atgl) protein expression localized in clusters of multilocular uncoupling protein 1 (Ucp1)-positive cells in female Aldh1a1(-/-) mice compared with males. Estrogen decreased Aldh1a3 expression, limiting conversion of retinaldehyde (Rald) to RA. Rald effectively induced Atgl levels via nongenomic mechanisms, demonstrating indirect regulation by estrogen. Experiments in transgenic mice expressing an RA receptor response element (RARE-lacZ) revealed HF diet-induced RARE activation in VF of females but not males. In humans, stromal cells isolated from VF of obese subjects also expressed higher levels of Aldh1 enzymes compared with lean subjects. Our data suggest that an HF diet mediates VF formation through a sex-specific autocrine Aldh1 switch, in which Rald-mediated lipolysis in Ucp1-positive visceral adipocytes is replaced by RA-mediated lipid accumulation. Our data suggest that Aldh1 is a potential target for sex-specific antiobesity therapy. PMID:22933113

  15. Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons.

    Science.gov (United States)

    Kim, Jae-Ick; Ganesan, Subhashree; Luo, Sarah X; Wu, Yu-Wei; Park, Esther; Huang, Eric J; Chen, Lu; Ding, Jun B

    2015-10-01

    Midbrain dopamine neurons are an essential component of the basal ganglia circuitry, playing key roles in the control of fine movement and reward. Recently, it has been demonstrated that γ-aminobutyric acid (GABA), the chief inhibitory neurotransmitter, is co-released by dopamine neurons. Here, we show that GABA co-release in dopamine neurons does not use the conventional GABA-synthesizing enzymes, glutamate decarboxylases GAD65 and GAD67. Our experiments reveal an evolutionarily conserved GABA synthesis pathway mediated by aldehyde dehydrogenase 1a1 (ALDH1a1). Moreover, GABA co-release is modulated by ethanol (EtOH) at concentrations seen in blood alcohol after binge drinking, and diminished ALDH1a1 leads to enhanced alcohol consumption and preference. These findings provide insights into the functional role of GABA co-release in midbrain dopamine neurons, which may be essential for reward-based behavior and addiction.

  16. Evaluation of alcohol dehydrogenase and aldehyde dehydrogenase enzymes as bi-enzymatic anodes in a membraneless ethanol microfluidic fuel cell

    Science.gov (United States)

    Galindo-de-la-Rosa, J.; Arjona, N.; Arriaga, L. G.; Ledesma-García, J.; Guerra-Balcázar, M.

    2015-12-01

    Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (AldH) enzymes were immobilized by covalent binding and used as the anode in a bi-enzymatic membraneless ethanol hybrid microfluidic fuel cell. The purpose of using both enzymes was to optimize the ethanol electro-oxidation reaction (EOR) by using ADH toward its direct oxidation and AldH for the oxidation of aldehydes as by-products of the EOR. For this reason, three enzymatic bioanode configurations were evaluated according with the location of enzymes: combined, vertical and horizontally separated. In the combined configuration, a current density of 16.3 mA cm-2, a voltage of 1.14 V and a power density of 7.02 mW cm-2 were obtained. When enzymes were separately placed in a horizontal and vertical position the ocp drops to 0.94 V and to 0.68 V, respectively. The current density also falls to values of 13.63 and 5.05 mA cm-2. The decrease of cell performance of bioanodes with separated enzymes compared with the combined bioanode was of 31.7% and 86.87% for the horizontal and the vertical array.

  17. Aldehyde dehydrogenase 3A1 is robustly upregulated in gastric cancer stem-like cells and associated with tumorigenesis.

    Science.gov (United States)

    Wu, Di; Mou, Yi-Ping; Chen, Ke; Cai, Jia-Qin; Zhou, Yu-Cheng; Pan, Yu; Xu, Xiao-Wu; Zhou, Wei; Gao, Jia-Qi; Chen, Ding-Wei; Zhang, Ren-Chao

    2016-08-01

    Enhanced aldehyde dehydrogenase (ALDH) activity has been shown to serve as a hallmark for cancer stem cells (CSCs). Recent evidence suggests that its role as a stem cell-related marker has come down to the specific isoform. However, little is known about the specific ALDH isoform contributing to aldefluor activity in gastric cancer. In this study, we isolated ALDHbright cells from 2 human gastric cancer cell lines MKN-45 and SGC‑7901 by using an Aldefluor assay and found elevated self-renewal, differentiation and tumorigenicity, as demonstration of stemness characteristics. We also found that ALDHbright cells expressed decreased levels of E-cadherin but increased levels of Snail and Vimentin, indication of an epithelial-mesenchymal transition (EMT) phenotype which may be responsible for the enhanced metastatic potential. Since further research and prognostic application based on ALDH prevalence require the quantification of the specific ALDH isoform, we characterized the expression of all 19 ALDH isoforms in the sorted gastric cancer cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Compared with the non-stem counterparts, robust upregulation of ALDH-3A1 was observed in these gastric cancer stem-like cells. Furthermore, we performed immunohistological analysis on 93 fixed patient gastric tumor samples and found that ALDH-3A1 expression correlated well with gastric cancer dysplasia and grades, differentiation, lymph node metastasis and cancer stage. Our data, therefore, provide strong evidence that ALDH-3A1 is a novel gastric cancer stem cell related marker with potential prognostic values and demonstrate a clear association between ALDH-3A1 prevalence and gastric cancer progression. PMID:27279633

  18. Aldehyde dehydrogenase 2 protects human umbilical vein endothelial cells against oxidative damage and increases endothelial nitric oxide production to reverse nitroglycerin tolerance.

    Science.gov (United States)

    Hu, X Y; Fang, Q; Ma, D; Jiang, L; Yang, Y; Sun, J; Yang, C; Wang, J S

    2016-06-10

    Medical nitroglycerin (glyceryl trinitrate, GTN) use is limited principally by tolerance typified by a decrease in nitric oxide (NO) produced by biotransformation. Such tolerance may lead to endothelial dysfunction by inducing oxidative stress. In vivo studies have demonstrated that aldehyde dehydrogenase 2 (ALDH2) plays important roles in GTN biotransformation and tolerance. Thus, modification of ALDH2 expression represents a potentially effective strategy to prevent and reverse GTN tolerance and endothelial dysfunction. In this study, a eukaryotic expression vector containing the ALDH2 gene was introduced into human umbilical vein endothelial cells (HUVECs) by liposome-mediated transfection. An indirect immunofluorescence assay showed that ALDH2 expression increased 24 h after transfection. Moreover, real-time polymerase chain reaction and western blotting revealed significantly higher ALDH2 mRNA and protein expression in the gene-transfected group than in the two control groups. GTN tolerance was induced by treating HUVECs with 10 mM GTN for 16 h + 10 min, which significantly decreased NO levels in control cells, but not in those transfected with ALDH2. Overexpression of ALDH2 increased cell survival against GTN-induced cytotoxicity and conferred protection from oxidative damage resulting from nitrate tolerance, accompanied by decreased production of intracellular reactive oxygen species and reduced expression of heme oxygenase 1. Furthermore, ALDH2 overexpression promoted Akt phosphorylation under GTN tolerance conditions. ALDH2 gene transfection can reverse and prevent tolerance to GTN through its bioactivation and protect against oxidative damage, preventing the development of endothelial dysfunction.

  19. Aldehyde dehydrogenases inhibition eradicates leukemia stem cells while sparing normal progenitors.

    Science.gov (United States)

    Venton, G; Pérez-Alea, M; Baier, C; Fournet, G; Quash, G; Labiad, Y; Martin, G; Sanderson, F; Poullin, P; Suchon, P; Farnault, L; Nguyen, C; Brunet, C; Ceylan, I; Costello, R T

    2016-01-01

    The vast majority of patients with acute myeloid leukemia (AML) achieve complete remission (CR) after standard induction chemotherapy. However, the majority subsequently relapse and die of the disease. A leukemia stem cell (LSC) paradigm has been invoked to explain this failure of CR to reliably translate into cure. Indeed, LSCs are highly enriched in CD34+CD38- leukemic cells that exhibit positive aldehyde dehydrogenase activity (ALDH+) on flow cytometry, these LSCs are resistant to currently existing treatments in AML such as cytarabine and anthracycline that, at the cost of great toxicity on normal cells, are highly active against the leukemic bulk, but spare the LSCs responsible for relapse. To try to combat the LSC population selectively, a well-characterized ALDH inhibitor by the trivial name of dimethyl ampal thiolester (DIMATE) was assessed on sorted CD34+CD38- subpopulations from AML patients and healthy patients. ALDH activity and cell viability were monitored by flow cytometry. From enzyme kinetic studies DIMATE is an active enzyme-dependent, competitive, irreversible inhibitor of ALDH1. On cells in culture, DIMATE is a powerful inhibitor of ALDHs 1 and 3, has a major cytotoxic activity on human AML cell lines. Moreover, DIMATE is highly active against leukemic populations enriched in LSCs, but, unlike conventional chemotherapy, DIMATE is not toxic for healthy hematopoietic stem cells which retained, after treatment, their self-renewing and multi-lineage differentiation capacity in immunodeficient mice, xenografted with human leukemic cells. DIMATE eradicates specifically human AML cells and spares healthy mouse hematologic cells. PMID:27611922

  20. Site-directed mutagenesis of aldehyde dehydrogenase-2 suggests three distinct pathways of nitroglycerin biotransformation.

    Science.gov (United States)

    Wenzl, M Verena; Beretta, Matteo; Griesberger, Martina; Russwurm, Michael; Koesling, Doris; Schmidt, Kurt; Mayer, Bernd; Gorren, Antonius C F

    2011-08-01

    To elucidate the mechanism underlying reduction of nitroglycerin (GTN) to nitric oxide (NO) by mitochondrial aldehyde dehydrogenase (ALDH2), we generated mutants of the enzyme lacking the cysteines adjacent to reactive Cys302 (C301S and C303S), the glutamate that participates as a general base in aldehyde oxidation (E268Q) or combinations of these residues. The mutants were characterized regarding acetaldehyde dehydrogenation, GTN-triggered enzyme inactivation, GTN denitration, NO formation, and soluble guanylate cyclase activation. Lack of the cysteines did not affect dehydrogenase activity but impeded GTN denitration, aggravated GTN-induced enzyme inactivation, and increased NO formation. A triple mutant lacking the cysteines and Glu268 catalyzed sustained formation of superstoichiometric amounts of NO and exhibited slower rates of inactivation. These results suggest three alternative pathways for the reaction of ALDH2 with GTN, all involving formation of a thionitrate/sulfenyl nitrite intermediate at Cys302 as the initial step. In the first pathway, which predominates in the wild-type enzyme and reflects clearance-based GTN denitration, the thionitrate apparently reacts with one of the adjacent cysteine residues to yield nitrite and a protein disulfide. The predominant reaction catalyzed by the single and double cysteine mutants requires Glu268 and results in irreversible enzyme inactivation. Finally, combined lack of the cysteines and Glu268 shifts the reaction toward formation of the free NO radical, presumably through homolytic cleavage of the sulfenyl nitrite intermediate. Although the latter reaction accounts for less than 10% of total turnover of GTN metabolism catalyzed by wild-type ALDH2, it is most likely essential for vascular GTN bioactivation.

  1. Aldehyde dehydrogenase 1a3 defines a subset of failing pancreatic β cells in diabetic mice.

    Science.gov (United States)

    Kim-Muller, Ja Young; Fan, Jason; Kim, Young Jung R; Lee, Seung-Ah; Ishida, Emi; Blaner, William S; Accili, Domenico

    2016-01-01

    Insulin-producing β cells become dedifferentiated during diabetes progression. An impaired ability to select substrates for oxidative phosphorylation, or metabolic inflexibility, initiates progression from β-cell dysfunction to β-cell dedifferentiation. The identification of pathways involved in dedifferentiation may provide clues to its reversal. Here we isolate and functionally characterize failing β cells from various experimental models of diabetes and report a striking enrichment in the expression of aldehyde dehydrogenase 1 isoform A3 (ALDH(+)) as β cells become dedifferentiated. Flow-sorted ALDH(+) islet cells demonstrate impaired glucose-induced insulin secretion, are depleted of Foxo1 and MafA, and include a Neurogenin3-positive subset. RNA sequencing analysis demonstrates that ALDH(+) cells are characterized by: (i) impaired oxidative phosphorylation and mitochondrial complex I, IV and V; (ii) activated RICTOR; and (iii) progenitor cell markers. We propose that impaired mitochondrial function marks the progression from metabolic inflexibility to dedifferentiation in the natural history of β-cell failure. PMID:27572106

  2. The longitudinal effect of the aldehyde dehydrogenase 2*2 allele on the risk for nonalcoholic fatty liver disease

    Science.gov (United States)

    Oniki, K; Morita, K; Watanabe, T; Kajiwara, A; Otake, K; Nakagawa, K; Sasaki, Y; Ogata, Y; Saruwatari, J

    2016-01-01

    Aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes and has a key role in protecting the liver. An elevated gamma-glutamyl transferase (GGT) level is related to oxidative stress and nonalcoholic fatty liver disease (NAFLD). We herein investigated the association between inactive ALDH2*2 allele (rs671) and the risk of NAFLD, including the relationship to the GGT level. A retrospective follow-up study (mean 5.4±1.1 years) was conducted among 341 Japanese health screening program participants. The receiver operating characteristic curve indicated that the GGT level predicted the development of NAFLD (area under the curve: 0.65, P<0.05) with a cutoff value of 25.5 IUl−1. The longitudinal risk of NAFLD was higher in the ALDH2*2 allele carriers than in the noncarriers (odds ratio (OR): 2.30, 95% confidence interval (CI): 1.21–4.40), and the risk was further increased among the *2 allele carriers with GGT values ⩾25.5 IUl−1 (OR: 4.28, 95% CI: 1.80–10.19). On the other hand, there were no significant changes in the subjects' body weight and body mass index during observation period. The ALDH2*2 allele, in relation to the GGT level, may potentially be a novel risk factor for NAFLD. PMID:27214654

  3. Aldehyde dehydrogenase activity selects for the holoclone phenotype in prostate cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► Isolated ALDHHi PC3 cells preferentially form primitive holoclone-type colonies. ► Primitive holoclone colonies are predominantly ALDHLo but contain rare ALDHHi cells. ► Holoclone-forming cells are not restricted to the ALDHHi population. ► ALDH phenotypic plasticity occurs in PC3 cells (ALDHLo to ALDHHi and vice versa). ► ALDHHi cells are observed but very rare in PC3 spheroids grown in stem cell medium. -- Abstract: Aldehyde dehydrogenase 1 (ALDH) activity is considered to be a marker of cancer stem cells (CSCs) in many tumour models, since these cells are more proliferative and tumourigenic than ALDHLo cells in experimental models. However it is unclear whether all CSC-like cells are within the ALDHHi population, or whether all ALDHHi cells are highly proliferative and tumourigenic. The ability to establish a stem cell hierarchy in vitro, whereby sub-populations of cells have differing proliferative and differentiation capacities, is an alternate indication of the presence of stem cell-like populations within cell lines. In this study, we have examined the interaction between ALDH status and the ability to establish a stem cell hierarchy in PC3 prostate cancer cells. We demonstrate that PC3 cells contain a stem cell hierarchy, and isolation of ALDHHi cells enriches for the most primitive holoclone population, however holoclone formation is not restricted to ALDHHi cells. In addition, we show that ALDH activity undergoes phenotypic plasticity, since the ALDHLo population can develop ALDHHi populations comparable to parental cells within 2 weeks in culture. Furthermore, we show that the majority of ALDHHi cells are found within the least primitive paraclone population, which is circumvented by culturing PC3 cells as spheroids in defined medium favouring stem cell characteristics. Although ALDHHi status enriches for holoclone formation, this activity may be mediated by a minority of ALDHHi cells.

  4. Inhibition of human alcohol and aldehyde dehydrogenases by acetaminophen: Assessment of the effects on first-pass metabolism of ethanol.

    Science.gov (United States)

    Lee, Yung-Pin; Liao, Jian-Tong; Cheng, Ya-Wen; Wu, Ting-Lun; Lee, Shou-Lun; Liu, Jong-Kang; Yin, Shih-Jiun

    2013-11-01

    Acetaminophen is one of the most widely used over-the-counter analgesic, antipyretic medications. Use of acetaminophen and alcohol are commonly associated. Previous studies showed that acetaminophen might affect bioavailability of ethanol by inhibiting gastric alcohol dehydrogenase (ADH). However, potential inhibitions by acetaminophen of first-pass metabolism (FPM) of ethanol, catalyzed by the human ADH family and by relevant aldehyde dehydrogenase (ALDH) isozymes, remain undefined. ADH and ALDH both exhibit racially distinct allozymes and tissue-specific distribution of isozymes, and are principal enzymes responsible for ethanol metabolism in humans. In this study, we investigated acetaminophen inhibition of ethanol oxidation with recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and inhibition of acetaldehyde oxidation with recombinant human ALDH1A1 and ALDH2. The investigations were done at near physiological pH 7.5 and with a cytoplasmic coenzyme concentration of 0.5 mM NAD(+). Acetaminophen acted as a noncompetitive inhibitor for ADH enzymes, with the slope inhibition constants (Kis) ranging from 0.90 mM (ADH2) to 20 mM (ADH1A), and the intercept inhibition constants (Kii) ranging from 1.4 mM (ADH1C allozymes) to 19 mM (ADH1A). Acetaminophen exhibited noncompetitive inhibition for ALDH2 (Kis = 3.0 mM and Kii = 2.2 mM), but competitive inhibition for ALDH1A1 (Kis = 0.96 mM). The metabolic interactions between acetaminophen and ethanol/acetaldehyde were assessed by computer simulation using inhibition equations and the determined kinetic constants. At therapeutic to subtoxic plasma levels of acetaminophen (i.e., 0.2-0.5 mM) and physiologically relevant concentrations of ethanol (10 mM) and acetaldehyde (10 μm) in target tissues, acetaminophen could inhibit ADH1C allozymes (12-26%) and ADH2 (14-28%) in the liver and small intestine, ADH4 (15-31%) in the stomach, and ALDH1A1 (16-33%) and ALDH2 (8.3-19%) in all 3 tissues. The

  5. Aldehyde Dehydrogenase 1 Is a Marker for Normal and Malignant Human Colonic Stem Cells (SC) and Tracks SC Overpopulation during Colon Tumorigenesis

    OpenAIRE

    Huang, Emina H.; Hynes, Mark J.; Zhang, Tao; Ginestier, Christophe; Dontu, Gabriela; Appelman, Henry; Fields, Jeremy Z.; Wicha, Max S.; Boman, Bruce M

    2009-01-01

    Although the concept that cancers originate from stem cells (SC) is becoming scientifically accepted, mechanisms by which SC contribute to tumor initiation and progression are largely unknown. For colorectal cancer (CRC), investigation of this problem has been hindered by a paucity of specific markers for identification and isolation of SC from normal and malignant colon. Accordingly, aldehyde dehydrogenase 1 (ALDH1) was investigated as a possible marker for identifying colonic SC and for tra...

  6. Inhibition of human alcohol and aldehyde dehydrogenases by aspirin and salicylate: assessment of the effects on first-pass metabolism of ethanol.

    Science.gov (United States)

    Lee, Shou-Lun; Lee, Yung-Pin; Wu, Min-Li; Chi, Yu-Chou; Liu, Chiu-Ming; Lai, Ching-Long; Yin, Shih-Jiun

    2015-05-01

    Previous studies have reported that aspirin significantly reduced the first-pass metabolism (FPM) of ethanol in humans thereby increasing adverse effects of alcohol. The underlying causes, however, remain poorly understood. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), principal enzymes responsible for metabolism of ethanol, are complex enzyme families that exhibit functional polymorphisms among ethnic groups and distinct tissue distributions. We investigated the inhibition profiles by aspirin and its major metabolite salicylate of ethanol oxidation by recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and acetaldehyde oxidation by ALDH1A1 and ALDH2, at pH 7.5 and 0.5 mM NAD(+). Competitive inhibition pattern was found to be a predominant type among the ADHs and ALDHs studied, although noncompetitive and uncompetitive inhibitions were also detected in a few cases. The inhibition constants of salicylate for the ADHs and ALDHs were considerably lower than that of aspirin with the exception of ADH1A that can be ascribed to a substitution of Ala-93 at the bottom of substrate pocket as revealed by molecular docking experiments. Kinetic inhibition equation-based simulations show at higher therapeutic levels of blood plasma salicylate (1.5 mM) that the decrease of activities at 2-10 mM ethanol for ADH1A/ADH2 and ADH1B2/ADH1B3 are predicted to be 75-86% and 31-52%, respectively, and that the activity decline for ALDH1A1 and ALDH2 at 10-50 μM acetaldehyde to be 62-73%. Our findings suggest that salicylate may substantially inhibit hepatic FPM of alcohol at both the ADH and ALDH steps when concurrent intaking aspirin.

  7. Inhibition of human alcohol and aldehyde dehydrogenases by aspirin and salicylate: assessment of the effects on first-pass metabolism of ethanol.

    Science.gov (United States)

    Lee, Shou-Lun; Lee, Yung-Pin; Wu, Min-Li; Chi, Yu-Chou; Liu, Chiu-Ming; Lai, Ching-Long; Yin, Shih-Jiun

    2015-05-01

    Previous studies have reported that aspirin significantly reduced the first-pass metabolism (FPM) of ethanol in humans thereby increasing adverse effects of alcohol. The underlying causes, however, remain poorly understood. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), principal enzymes responsible for metabolism of ethanol, are complex enzyme families that exhibit functional polymorphisms among ethnic groups and distinct tissue distributions. We investigated the inhibition profiles by aspirin and its major metabolite salicylate of ethanol oxidation by recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and acetaldehyde oxidation by ALDH1A1 and ALDH2, at pH 7.5 and 0.5 mM NAD(+). Competitive inhibition pattern was found to be a predominant type among the ADHs and ALDHs studied, although noncompetitive and uncompetitive inhibitions were also detected in a few cases. The inhibition constants of salicylate for the ADHs and ALDHs were considerably lower than that of aspirin with the exception of ADH1A that can be ascribed to a substitution of Ala-93 at the bottom of substrate pocket as revealed by molecular docking experiments. Kinetic inhibition equation-based simulations show at higher therapeutic levels of blood plasma salicylate (1.5 mM) that the decrease of activities at 2-10 mM ethanol for ADH1A/ADH2 and ADH1B2/ADH1B3 are predicted to be 75-86% and 31-52%, respectively, and that the activity decline for ALDH1A1 and ALDH2 at 10-50 μM acetaldehyde to be 62-73%. Our findings suggest that salicylate may substantially inhibit hepatic FPM of alcohol at both the ADH and ALDH steps when concurrent intaking aspirin. PMID:25772736

  8. Alcohol Dehydrogenase-1B (rs1229984 and Aldehyde Dehydrogenase-2 (rs671 Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men.

    Directory of Open Access Journals (Sweden)

    Akira Yokoyama

    Full Text Available Elevated serum triglyceride (TG and high-density-lipoprotein cholesterol (HDL-C levels are common in drinkers. The fast-metabolizing alcohol dehydrogenase-1B encoded by the ADH1B*2 allele (vs. ADH1B*1/*1 genotype and inactive aldehyde dehydrogenase-2 encoded by the ALDH2*2 allele (vs. ALDH2*1/*1 genotype modify ethanol metabolism and are prevalent (≈90% and ≈40%, respectively in East Asians. We attempted to evaluate the associations between the ADH1B and ALDH2 genotypes and lipid levels in alcoholics.The population consisted of 1806 Japanese alcoholic men (≥40 years who had undergone ADH1B and ALDH2 genotyping and whose serum TG, total cholesterol, and HDL-C levels in the fasting state had been measured within 3 days after admission.High serum levels of TG (≥150 mg/dl, HDL-C (>80 mg/dl, and low-density-lipoprotein cholesterol (LDL-C calculated by the Friedewald formula ≥140 mg/dl were observed in 24.3%, 16.8%, and 15.6%, respectively, of the subjects. Diabetes, cirrhosis, smoking, and body mass index (BMI affected the serum lipid levels. Multivariate analysis revealed that the presence of the ADH1B*2 allele and the active ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval for a high TG level (2.22 [1.67-2.94] and 1.39 [0.99-1.96], respectively, and decreased the OR for a high HDL-C level (0.37 [0.28-0.49] and 0.51 [0.37-0.69], respectively. The presence of the ADH1B*2 allele decreased the OR for a high LDL-C level (0.60 [0.45-0.80]. The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs for high TG levels and lowest OR for a high HDL-C level. The genotype effects were more prominent in relation to the higher levels of TG (≥220 mg/dl and HDL-C (≥100 mg/dl.The fast-metabolizing ADH1B and active ALDH2, and especially a combination of the two were strongly associated with higher serum TG levels and lower serum HDL-C levels of alcoholics. The fast-metabolizing ADH1B was associated with lower serum LDL

  9. Low expression of aldehyde deyhdrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer

    International Nuclear Information System (INIS)

    Aldehyde deyhdrogenase 1 (ALDH1) has been characterised as a cancer stem cell marker in different types of tumours. Additionally, it plays a pivotal role in gene regulation and endows tumour cells with augmented chemoresistance. Recently, ALDH1A1 has been described as a prognostic marker in a pancreatic cancer tissue microarray. The aim of this study was to reevaluate the expression of ALDH1A1 as a prognostic marker on whole-mount tissue sections. Real-time-quantitative-PCR (qRT-PCR) and Western blotting were used to evaluate the expression profile of ALDH1A1 in seven pancreatic cancer cell lines and one non-malignant pancreatic cell line. Immunostaining against ALDH1A1 and Ki-67 was performed on paraffin-embedded samples from 97 patients with pancreatic cancer. The immunohistochemical results were correlated to histopathological and clinical data. qRT-PCR and Western blotting revealed a different expression pattern of ALDH1A1 in different malignant and non-malignant pancreatic cell lines. Immunohistochemical analysis demonstrated that ALDH1A1 was confined to the cellular cytoplasm and occurred in 72 cases (74%), whereas it was negative in 25 cases (26%). High expression of ALDH1A1 was significantly correlated to an increased proliferation rate (Spearman correlation, p = 0.01). Univariate and multivariate analyses showed that decreased expression of ALDH1A1 is an independent adverse prognostic factor for overall survival. Immunonhistochemical analysis on whole-mount tissue slides revealed that ALDH1A1 is more abundantly expressed in pancreatic cancer than initially reported by a tissue microarray analysis. Moreover, high expression of ALDH1A1 correlated significantly with the proliferation of tumour cells. Intriguingly, this study is the first which identifies low expression of ALDH1A1 as an independent adverse prognostic marker for overall survival in pancreatic cancer

  10. ALDH1A Isozymes Are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets

    OpenAIRE

    Luo, Yuchun; Dallaglio, Katiuscia; Chen, Ying; Robinson, William A.; Robinson, Steven E.; McCarter, Martin D; Wang, Jianbin; Gonzalez, Rene; Thompson, David C.; David A Norris; Roop, Dennis R.; Vasiliou, Vasilis; Fujita, Mayumi

    2012-01-01

    Although the concept of cancer stem cells (CSCs) is well accepted for many tumors, the existence of such cells in human melanoma has been the subject of debate. In the present study, we demonstrate the existence of human melanoma cells that fulfill the criteria for CSCs (self-renewal and differentiation) by serially xenotransplanting cells into NOD/SCID mice. These cells possess high aldehyde dehydrogenase (ALDH) activity with ALDH1A1 and ALDH1A3 being the predominant ALDH isozymes. ALDH-posi...

  11. Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat.

    Science.gov (United States)

    Badejo, Adeleke M; Hodnette, Chris; Dhaliwal, Jasdeep S; Casey, David B; Pankey, Edward; Murthy, Subramanyam N; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J

    2010-09-01

    It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was approximately 1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat.

  12. Molecular and Catalytic Properties of the Aldehyde Dehydrogenase of Gluconacetobacter diazotrophicus, a Quinoheme Protein Containing Pyrroloquinoline Quinone, Cytochrome b, and Cytochrome c▿

    Science.gov (United States)

    Gómez-Manzo, S.; Chavez-Pacheco, J. L.; Contreras-Zentella, M.; Sosa-Torres, M. E.; Arreguín-Espinosa, R.; Pérez de la Mora, M.; Membrillo-Hernández, J.; Escamilla, J. E.

    2010-01-01

    Several aldehyde dehydrogenase (ALDH) complexes have been purified from the membranes of acetic acid bacteria. The enzyme structures and the chemical nature of the prosthetic groups associated with these enzymes remain a matter of debate. We report here on the molecular and catalytic properties of the membrane-bound ALDH complex of the diazotrophic bacterium Gluconacetobacter diazotrophicus. The purified ALDH complex is a heterodimer comprising two subunits of 79.7 and 50 kDa, respectively. Reversed-phase high-pressure liquid chromatography (HPLC) and electron paramagnetic resonance spectroscopy led us to demonstrate, for the first time, the unequivocal presence of a pyrroloquinoline quinone prosthetic group associated with an ALDH complex from acetic acid bacteria. In addition, heme b was detected by UV-visible light (UV-Vis) spectroscopy and confirmed by reversed-phase HPLC. The smaller subunit bears three cytochromes c. Aliphatic aldehydes, but not formaldehyde, were suitable substrates. Using ferricyanide as an electron acceptor, the enzyme showed an optimum pH of 3.5 that shifted to pH 7.0 when phenazine methosulfate plus 2,6-dichlorophenolindophenol were the electron acceptors. Acetaldehyde did not reduce measurable levels of the cytochrome b and c centers; however, the dithionite-reduced hemes were conveniently oxidized by ubiquinone-1; this finding suggests that cytochrome b and the cytochromes c constitute an intramolecular redox sequence that delivers electrons to the membrane ubiquinone. PMID:20802042

  13. Isoflurane preconditioning confers cardioprotection by activation of ALDH2.

    Directory of Open Access Journals (Sweden)

    Xiao-E Lang

    Full Text Available The volatile anesthetic, isoflurane, protects the heart from ischemia/reperfusion (I/R injury. Aldehyde dehydrogenase 2 (ALDH2 is thought to be an endogenous mechanism against ischemia-reperfusion injury possibly through detoxification of toxic aldehydes. We investigated whether cardioprotection by isoflurane depends on activation of ALDH2.Anesthetized rats underwent 40 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups: untreated controls, isoflurane preconditioning with and without an ALDH2 inhibitor, the direct activator of ALDH2 or a protein kinase C (PKCε inhibitor. Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide. Isolated neonatal cardiomyocytes were treated with hypoxia followed by reoxygenation. Hypoxia/reoxygenation (H/R increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2. In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2. Activation of ALDH2 and cardioprotection by isoflurane were substantially blocked by the PKCε inhibitor. Activation of ALDH2 by mitochondrial PKCε plays an important role in the cardioprotection of isoflurane in myocardium I/R injury.

  14. A coniferyl aldehyde dehydrogenase gene from Pseudomonas sp. strain HR199 enhances the conversion of coniferyl aldehyde by Saccharomyces cerevisiae.

    Science.gov (United States)

    Adeboye, Peter Temitope; Olsson, Lisbeth; Bettiga, Maurizio

    2016-07-01

    The conversion of coniferyl aldehyde to cinnamic acids by Saccharomyces cerevisiae under aerobic growth conditions was previously observed. Bacteria such as Pseudomonas have been shown to harbor specialized enzymes for converting coniferyl aldehyde but no comparable enzymes have been identified in S. cerevisiae. CALDH from Pseudomonas was expressed in S. cerevisiae. An acetaldehyde dehydrogenase (Ald5) was also hypothesized to be actively involved in the conversion of coniferyl aldehyde under aerobic growth conditions in S. cerevisiae. In a second S. cerevisiae strain, the acetaldehyde dehydrogenase (ALD5) was deleted. A prototrophic control strain was also engineered. The engineered S. cerevisiae strains were cultivated in the presence of 1.1mM coniferyl aldehyde under aerobic condition in bioreactors. The results confirmed that expression of CALDH increased endogenous conversion of coniferyl aldehyde in S. cerevisiae and ALD5 is actively involved with the conversion of coniferyl aldehyde in S. cerevisiae. PMID:27070284

  15. Increased Expression of Aldehyde Dehydrogenase 2 Reduces Renal Cell Apoptosis During Ischemia/Reperfusion Injury After Hypothermic Machine Perfusion.

    Science.gov (United States)

    Zhong, Zibiao; Hu, Qianchao; Fu, Zhen; Wang, Ren; Xiong, Yan; Zhang, Yang; Liu, Zhongzhong; Wang, Yanfeng; Ye, Qifa

    2016-06-01

    Hypothermic machine perfusion (MP) can reduce graft's injury after kidney transplantation; however, the mechanism has not been elucidated. In the past decade, many studies showed that aldehyde dehydrogenase 2 (ALDH2) is a protease which can inhibit cell apoptosis. Therefore, this study aims to explore whether ALDH2 takes part in reducing organ damage after MP. Eighteen healthy male New Zealand rabbits (12 weeks old, weight 3.0 ± 0.3 kg) were randomly divided into three groups: normal group, MP group, and cold storage (CS) group (n = 6). The left kidney of rabbits underwent warm ischemia for 35 min through clamping the left renal pedicle and then reperfusion for 1 h. Left kidneys were preserved by MP or CS (4°C for 4 h) in vivo followed by the right nephrectomy and 24-h reperfusion, and then the specimens and blood were collected. Finally, concentration of urine creatinine (Cr), blood urea nitrogen (BUN), and 4-HNE were tested. Renal apoptosis was detected by TUNEL staining, and the expression of ALDH2, cleaved-caspase 3, bcl-2/ bax, MAPK in renal tissue was detected by immunohistochemistry or Western blot; 24 h after surgery, the concentration of Cr in MP group was 355 ± 71μmol/L, in CS group was 511 ± 44 μmol/L (P bcl-2/bax in MP group was significantly higher than that in CS group (P < 0.05); expression of cleaved caspase-3 in both MP and CS group significantly increased as compared with that in normal group (P < 0.05). In conclusion, increased expression of ALDH2 can reduce the renal cell apoptosis through inhibiting MAPK pathway during ischemia/reperfusion injury (IRI) after hypothermic MP. PMID:26582147

  16. Variation of transition-state structure as a function of the nucleotide in reactions catalyzed by dehydrogenases. 1. Liver alcohol dehydrogenase with benzyl alcohol and yeast aldehyde dehydrogenase with benzaldehyde.

    Science.gov (United States)

    Scharschmidt, M; Fisher, M A; Cleland, W W

    1984-11-01

    Primary intrinsic deuterium and 13C isotope effects have been determined for liver (LADH) and yeast (YADH) alcohol dehydrogenases with benzyl alcohol as substrate and for yeast aldehyde dehydrogenase (ALDH) with benzaldehyde as substrate. These values have also been determined for LADH as a function of changing nucleotide substrate. As the redox potential of the nucleotide changes from -0.320 V with NAD to -0.258 V with acetylpyridine-NAD, the product of primary and secondary deuterium isotope effects rises from 4 toward 6.5, while the primary 13C isotope effect drops from 1.025 to 1.012, suggesting a trend from a late transition state with NAD to one that is more symmetrical. The values of Dk (again the product of primary and secondary isotope effects) and 13k for YADH with NAD are 7 and 1.023, suggesting for this very slow reaction a more stretched, and thus symmetrical, transition state. With ALDH and NAD, the primary 13C isotope effect on the hydride transfer step lies in the range 1.3-1.6%, and the alpha-secondary deuterium isotope effect on the same step is at least 1.22, but 13C isotope effects on formation of the thiohemiacetal intermediate and on the addition of water to the thio ester intermediate are less than 1%. On the basis of the relatively large 13C isotope effects, we conclude that carbon motion is involved in the hydride transfer steps of dehydrogenase reactions.

  17. Comparative genomics of aldehyde dehydrogenase 5a1 (succinate semialdehyde dehydrogenase and accumulation of gamma-hydroxybutyrate associated with its deficiency

    Directory of Open Access Journals (Sweden)

    Malaspina Patrizia

    2009-01-01

    Full Text Available Abstract Succinic semialdehyde dehydrogenase (SSADH; aldehyde dehydrogenase 5A1 [ALDH5A1]; locus 6p22 occupies a central position in central nervous system (CNS neurotransmitter metabolism as one of two enzymes necessary for γ-aminobutyric acid (GABA recycling from the synaptic cleft. Its importance is highlighted by the neurometabolic disease associated with its inherited deficiency in humans, as well as the severe epileptic phenotype observed in Aldh5a1-/- knockout mice. Expanding evidence now suggests, however, that even subtle decreases in human SSADH activity, associated with rare and common single nucleotide polymorphisms, may produce subclinical pathological effects. SSADH, in conjunction with aldo-keto reductase 7A2 (AKR7A2, represent two neural enzymes responsible for further catabolism of succinic semialdehyde, producing either succinate (SSADH or γ-hydroxybutyrate (GHB; AKR7A2. A GABA analogue, GHB is a short-chain fatty alcohol with unusual properties in the CNS and a long pharmacological history. Moreover, SSADH occupies a further role in the CNS as the enzyme responsible for further metabolism of the lipid peroxidation aldehyde 4-hydroxy-2-nonenal (4-HNE, an intermediate known to induce oxidant stress. Accordingly, subtle decreases in SSADH activity may have the capacity to lead to regional accumulation of neurotoxic intermediates (GHB, 4-HNE. Polymorphisms in SSADH gene structure may also associate with quantitative traits, including intelligence quotient and life expectancy. Further population-based studies of human SSADH activity promise to reveal additional properties of its function and additional roles in CNS tissue.

  18. ALDH1A3, a metabolic target for cancer diagnosis and therapy.

    Science.gov (United States)

    Duan, Jiang-Jie; Cai, Jiao; Guo, Yu-Feng; Bian, Xiu-Wu; Yu, Shi-Cang

    2016-09-01

    Metabolism reprogramming has been linked with the initiation, metastasis, and recurrence of cancer. The aldehyde dehydrogenase (ALDH) family is the most important enzyme system for aldehyde metabolism. The human ALDH family is composed of 19 members. ALDH1A3 participates in various physiological processes in human cells by oxidizing all-trans-retinal to retinoic acid. ALDH1A3 expression is regulated by many factors, and it is associated with the development, progression, and prognosis of cancers. In addition, ALDH1A3 influences a diverse range of biological characteristics within cancer stem cells and can act as a marker for these cells. Thus, growing evidence indicates that ALDH1A3 has the potential to be used as a target for cancer diagnosis and therapy. PMID:26991532

  19. Taraxerone enhances alcohol oxidation via increases of alcohol dehyderogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities and gene expressions.

    Science.gov (United States)

    Sung, Chang-Keun; Kim, Seung-Mi; Oh, Chang-Jin; Yang, Sun-A; Han, Byung-Hee; Mo, Eun-Kyoung

    2012-07-01

    The present study, taraxerone (d-friedoolean-14-en-3-one) was isolated from Sedum sarmentosum with purity 96.383%, and its enhancing effects on alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities were determined: EC(50) values were 512.42 ± 3.12 and 500.16 ± 3.23 μM for ADH and ALDH, respectively. In order to obtain more information on taraxerone related with the alcohol metabolism, 40% ethanol (5 mL/kg body weight) with 0.5-1mM of taraxerone were administered to mice. The plasma alcohol and acetaldehyde concentrations of taraxerone-treated groups were significantly lowered than those of the control group (p<0.01): approximately 20-67% and 7-57% lowered for plasma alcohol and acetaldehyde, respectively. Compare to the control group, the ADH and ALDH expressions in the liver tissues were abruptly increased in the taraxerone-treated groups after ethanol exposure. In addition, taraxerone prevented catalase, superoxide dismutase, and reduced glutathione concentrations from the decrease induced by ethanol administration with the concentration dependent manner.

  20. Effect of Aldehyde Dehydrogenase 2 Gene Polymorphism on Hemodynamics After Nitroglycerin Intervention in Northern Chinese Han Population

    Directory of Open Access Journals (Sweden)

    Jia-Qi Xia

    2015-01-01

    Full Text Available Background: Nitroglycerin (NTG is one of the few immediate treatments for acute angina. Aldehyde dehydrogenase 2 (ALDH2 is a key enzyme in the human body that facilitates the biological metabolism of NTG. The biological mechanism of NTG serves an important function in NTG efficacy. Some reports still contradict the results that the correlation between ALDH2 gene polymorphisms and NTG and its clinical efficacy is different. However, data on NTG measurement by pain relief are subjective. This study aimed to investigate the influence of ALDH2 gene polymorphism on intervention with sublingual NTG using noninvasive hemodynamic parameters of cardiac output (CO and systemic vascular resistance (SVR in Northern Chinese Han population. Methods: This study selected 559 patients from the Affiliated Hospital of Qingdao University. A total of 203 patients presented with coronary heart disease (CHD and 356 had non-CHD (NCHD cases. All patient ALDH2 genotypes (G504A were detected and divided into two types: Wild (GG and mutant (GA/AA. Among the CHD group, 103 were wild-type cases, and 100 were mutant-type cases. Moreover, 196 cases were wild-type, and 160 cases were mutant type among the NCHD volunteers. A noninvasive hemodynamic detector was used to monitor the CO and the SVR at the 0, 5, and 15 minute time points after medication with 0.5 mg sublingual NTG. Two CO and SVR indicators were used for a comparative analysis of all case genotypes. Results: Both CO and SVR indicators significantly differed between the wild and mutant genotypes at various time points after intervention with sublingual NTG at 5 and 15 minutes in the NCHD (F = 16.460, 15.003, P = 0.000, 0.000 and CHD groups (F = 194.482, 60.582, P = 0.000, 0.000. All CO values in the wild-type case of both NCHD and CHD groups increased, whereas those in the mutant type decreased. The CO and ΔCO differences were statistically significant (P < 0.05; P < 0.05. The SVR and ΔSVR changed between the wild

  1. Expression of aldehyde dehydrogenase 1 in colon cancer

    Institute of Scientific and Technical Information of China (English)

    Yi Hou; Yi-Yi Liu; Xiao-Kun Zhao

    2013-01-01

    Objective: To study the expression of ALDH1 in colon cancer and its clinical significance. Methods: The expression of ALDH1 was examined in 98 surgical specimens of primary colonic carcinoma and 15 normal colon tissues with immunohistochemistry method. The correlations of the expression with clinicopathological parameters and prognosis of colon cancer were analyzed.Results:The positive rate of expression of ALDH1 was 76.5% (75/98) in the cancer tissues and 13.3% (2/15) in normal colon tissues. There were an obvious statistical difference (P<0.05) between the two groups. The ALDH1 expression was significantly correlated with the histological grade, TNM stages and lymph node metastasis in colon cancer (P<0.05). It was also related with patients’ survival time, those with positive expressions had a poor prognosis (P<0.05). Conclusions: The results suggeste that the overexpression of ALDH1 plays important roles in proliferation and progression in colon cancer, the ALDH1 may be a valuable marker to predict the biological behavior and trend of metastasis of colon cancer.

  2. Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer

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    Iniesta Pilar

    2011-08-01

    Full Text Available Abstract Background Mortality rates for advanced lung cancer have not declined for decades, even with the implementation of novel chemotherapeutic regimens or the use of tyrosine kinase inhibitors. Cancer Stem Cells (CSCs are thought to be responsible for resistance to chemo/radiotherapy. Therefore, targeting CSCs with novel compounds may be an effective approach to reduce lung tumor growth and metastasis. We have isolated and characterized CSCs from non-small cell lung cancer (NSCLC cell lines and measured their telomerase activity, telomere length, and sensitivity to the novel telomerase inhibitor MST312. Results The aldehyde dehydrogenase (ALDH positive lung cancer cell fraction is enriched in markers of stemness and endowed with stem cell properties. ALDH+ CSCs display longer telomeres than the non-CSC population. Interestingly, MST312 has a strong antiproliferative effect on lung CSCs and induces p21, p27 and apoptosis in the whole tumor population. MST312 acts through activation of the ATM/pH2AX DNA damage pathway (short-term effect and through decrease in telomere length (long-term effect. Administration of this telomerase inhibitor (40 mg/kg in the H460 xenograft model results in significant tumor shrinkage (70% reduction, compared to controls. Combination therapy consisting of irradiation (10Gy plus administration of MST312 did not improve the therapeutic efficacy of the telomerase inhibitor alone. Treatment with MST312 reduces significantly the number of ALDH+ CSCs and their telomeric length in vivo. Conclusions We conclude that antitelomeric therapy using MST312 mainly targets lung CSCs and may represent a novel approach for effective treatment of lung cancer.

  3. ALDH2 protects against stroke by clearing 4-HNE

    Institute of Scientific and Technical Information of China (English)

    Jin-Min Guo; Ai-Jun Liu; Pu Zang; Wen-Zhe Dong; Li Ying; Wei Wang; Pu Xu

    2013-01-01

    Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that metabolizes ethanol and toxic aldehydes such as 4-hydroxy-2-nonenal (4-HNE).Using an unbiased proteomic search,we identified ALDH2 deficiency in stroke-prone spontaneously hypertensive rats (SHR-SP) as compared with spontaneously hypertensive rats (SHR).We concluded the causative role of ALDH2 deficiency in neuronal injury as overexpression or activation of ALDH2conferred neuroprotection by clearing 4-HNE in in vitro studies.Further,ALDH2-knockdown rats revealed the absence of neuroprotective effects of PKCε.Moderate ethanol administration that is known to exert protection against stroke was shown to enhance the detoxification of 4-HNE,and to protect against ischemic cerebral injury through the PKCε-ALDH2 pathway.In SHR-SP,serum 4-HNE level was persistently elevated and correlated inversely with the lifespan.The role of 4-HNE in stroke in humans was also suggested by persistent elevation of its plasma levels for at least 6 months after stroke.Lastly,we observed that 21 of 1 242 subjects followed for 8 years who developed stroke had higher initial plasma 4-HNE levels than those who did not develop stroke.These findings suggest that activation of the ALDH2 pathway may serve as a useful index in the identification of stroke-prone subjects,and the ALDH2 pathway may be a potential target of therapeutic intervention in stroke.

  4. Pyruvate:ferredoxin oxidoreductase and bifunctional aldehyde-alcohol dehydrogenase are essential for energy metabolism under oxidative stress in Entamoeba histolytica.

    Science.gov (United States)

    Pineda, Erika; Encalada, Rusely; Rodríguez-Zavala, José S; Olivos-García, Alfonso; Moreno-Sánchez, Rafael; Saavedra, Emma

    2010-08-01

    The in vitro Entamoeba histolytica pyruvate:ferredoxin oxidoreductase (EhPFOR) kinetic properties and the effect of oxidative stress on glycolytic pathway enzymes and fluxes in live trophozoites were evaluated. EhPFOR showed a strong preference for pyruvate as substrate over other oxoacids. The enzyme was irreversibly inactivated by a long period of saturating O(2) exposure (IC(50) 0.034 mm), whereas short-term exposure ( 90% inhibition allowed for partial restoration by addition of Fe(2+). CoA and acetyl-CoA prevented, whereas pyruvate exacerbated, inactivation induced by short-term saturating O(2) exposure. Superoxide dismutase was more effective than catalase in preventing the inactivation, indicating that reactive oxygen species (ROS) were involved. Hydrogen peroxide caused inactivation in an Fe(2+)-reversible fashion that was not prevented by the coenzymes, suggesting different mechanisms of enzyme inactivation by ROS. Structural analysis on an EhPFOR 3D model suggested that the protection against ROS provided by coenzymes could be attributable to their proximity to the Fe-S clusters. After O(2) exposure, live parasites displayed decreased enzyme activities only for PFOR (90%) and aldehyde dehydrogenase (ALDH; 68%) of the bifunctional aldehyde-alcohol dehydrogenase (EhADH2), whereas acetyl-CoA synthetase remained unchanged, explaining the increased acetate and lowered ethanol fluxes. Remarkably, PFOR and ALDH activities were restored after return of the parasites to normoxic conditions, which correlated with higher ethanol and lower acetate fluxes. These results identified amebal PFOR and ALDH of EhADH2 activities as markers of oxidative stress, and outlined their relevance as significant controlling steps of energy metabolism in parasites subjected to oxidative stress. PMID:20629749

  5. Effects of ALDH2*2 on Alcohol Problem Trajectories of Asian American College Students

    OpenAIRE

    Luczak, Susan E.; Yarnell, Lisa M.; Prescott, Carol A.; Myers, Mark G.; Liang, Tiebing; Wall, Tamara L.

    2014-01-01

    The variant aldehyde dehydrogenase allele, ALDH2*2, consistently has been associated with protection against alcohol dependence, but the mechanism underlying this process is not known. This study examined growth trajectories of alcohol consumption (frequency, average quantity, binge drinking, maximum drinks) and problems over the college years and then tested whether the ALDH2 genotype mediated or moderated the relationship between alcohol consumption and problems. Asian American college stud...

  6. Relationship between genetic polymorphisms of ALDH2 and ADH1B and esophageal cancer risk:A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Akira; Yokoyama; Tetsuji; Yokoyama

    2010-01-01

    AIM:To evaluate the contribution of alcohol dehydrogenase-1B(ADH1B)and aldehyde dehydrogenase-2 (ALDH2)polymorphisms to the risk of esophageal cancer.METHODS:Nineteen articles were included by searching MEDLINE,EMBASE and the Chinese Biomedical Database,13 on ADH1B and 18 on ALDH2.We performed a meta-analysis of case-control studies including 13 studies on ADH1B(cases/controls:2390/7100)and 18 studies on ALDH2(2631/6030).RESULTS:The crude odds ratio[OR(95%confidence interval)]was 2.91(2.04-4.14)for ADH1B*1/...

  7. Acetaldehyde metabolism by liver mitochondrial ALDH from UChA and UChB rats: effect of inhibitors.

    Science.gov (United States)

    Tampier, L; Sánchez, E; Quintanilla, M E

    1996-01-01

    We have observed that blood acetaldehyde (AcH) levels after an ethanol dose were significantly higher in disulfiram-pre-treated UChA (low ethanol consumer) than in UChB (high ethanol consumer) rats. In order to explore these results further, we studied the effect of disulfiram (300 mg/kg i.p.) and chlorpropamide (80) mg/kg i.p.) pre-treatment on blood AcH levels after oral ethanol (60 mmol/kg) and on AcH metabolism by liver mitochondrial aldehyde(s) dehydrogenase(s) from UChA and UChB rats. AcH metabolism by liver mitochondrial aldehyde dehydrogenase (ALDH) was studied by following AcH disappearance rate and the formation of NADH at 340 nm in the incubation medium. The results showed that chlorpropamide, like disulfiram, produced a higher blood AcH level consistent with a greater inhibition of the low-Km mitochondrial ALDH in the UChA rats than in the UChB rats. These drugs did not inhibit the high Km mitochondrial ALDH. Kinetic studies of mitochondrial ALDH show that low-Km mitochondrial ALDH from UChB rats exhibits a higher affinity for NAD than UChA rats. This observation could explain the different inhibition of ALDH by both drugs, assuming that the inhibitors reduce NAD availability, the rate limiting step in the mitochondrial ALDH oxidation.

  8. The oxidative fermentation of ethanol in Gluconacetobacter diazotrophicus is a two-step pathway catalyzed by a single enzyme: alcohol-aldehyde Dehydrogenase (ADHa).

    Science.gov (United States)

    Gómez-Manzo, Saúl; Escamilla, José E; González-Valdez, Abigail; López-Velázquez, Gabriel; Vanoye-Carlo, América; Marcial-Quino, Jaime; de la Mora-de la Mora, Ignacio; Garcia-Torres, Itzhel; Enríquez-Flores, Sergio; Contreras-Zentella, Martha Lucinda; Arreguín-Espinosa, Roberto; Kroneck, Peter M H; Sosa-Torres, Martha Elena

    2015-01-01

    Gluconacetobacter diazotrophicus is a N2-fixing bacterium endophyte from sugar cane. The oxidation of ethanol to acetic acid of this organism takes place in the periplasmic space, and this reaction is catalyzed by two membrane-bound enzymes complexes: the alcohol dehydrogenase (ADH) and the aldehyde dehydrogenase (ALDH). We present strong evidence showing that the well-known membrane-bound Alcohol dehydrogenase (ADHa) of Ga. diazotrophicus is indeed a double function enzyme, which is able to use primary alcohols (C2-C6) and its respective aldehydes as alternate substrates. Moreover, the enzyme utilizes ethanol as a substrate in a reaction mechanism where this is subjected to a two-step oxidation process to produce acetic acid without releasing the acetaldehyde intermediary to the media. Moreover, we propose a mechanism that, under physiological conditions, might permit a massive conversion of ethanol to acetic acid, as usually occurs in the acetic acid bacteria, but without the transient accumulation of the highly toxic acetaldehyde. PMID:25574602

  9. The Oxidative Fermentation of Ethanol in Gluconacetobacter diazotrophicus Is a Two-Step Pathway Catalyzed by a Single Enzyme: Alcohol-Aldehyde Dehydrogenase (ADHa

    Directory of Open Access Journals (Sweden)

    Saúl Gómez-Manzo

    2015-01-01

    Full Text Available Gluconacetobacter diazotrophicus is a N2-fixing bacterium endophyte from sugar cane. The oxidation of ethanol to acetic acid of this organism takes place in the periplasmic space, and this reaction is catalyzed by two membrane-bound enzymes complexes: the alcohol dehydrogenase (ADH and the aldehyde dehydrogenase (ALDH. We present strong evidence showing that the well-known membrane-bound Alcohol dehydrogenase (ADHa of Ga. diazotrophicus is indeed a double function enzyme, which is able to use primary alcohols (C2–C6 and its respective aldehydes as alternate substrates. Moreover, the enzyme utilizes ethanol as a substrate in a reaction mechanism where this is subjected to a two-step oxidation process to produce acetic acid without releasing the acetaldehyde intermediary to the media. Moreover, we propose a mechanism that, under physiological conditions, might permit a massive conversion of ethanol to acetic acid, as usually occurs in the acetic acid bacteria, but without the transient accumulation of the highly toxic acetaldehyde.

  10. Conversion of Suspected Food Carcinogen 5-Hydroxymethylfurfural by Sulfotransferases and Aldehyde Dehydrogenases in Postmitochondrial Tissue Preparations of Humans, Mice, and Rats.

    Science.gov (United States)

    Sachse, Benjamin; Meinl, Walter; Glatt, Hansruedi; Monien, Bernhard H

    2016-01-01

    The food contaminant 5-hydroxymethylfurfural (HMF) is formed by heat- and acid-catalyzed reactions from carbohydrates. More than 80% of HMF is metabolized by oxidation of the aldehyde group in mice and rats. Sulfo conjugation yields mutagenic 5-sulfoxymethylfurfural, the probable cause for the neoplastic effects observed in HMF-treated rodents. Considerable metabolic differences between species hinder assessing the tumorigenic risk associated with human dietary HMF uptake. Here, we assayed HMF turnover catalyzed by sulfotransferases or by aldehyde dehydrogenases (ALDHs) in postmitochondrial preparations from liver, kidney, colon, and lung of humans, mice, and rats. The tissues-specific clearance capacities of HMF sulfo conjugation (CL(SC)) and ALDH-catalyzed oxidation (CL(OX)) were concentrated to the liver. The hepatic clearance CL(SC) in mice (males: 487 µl/min/kg bw, females: 2520 µl/min/kg bw) and rats (males: 430 µl/min/kg bw, females: 198 µl/min/kg bw) were considerably higher than those in humans (males: 21.2 µl/min/kg bw, females: 32.2 µl/min/kg bw). The ALDH-related clearance rates CLOX in mice (males: 3400 ml/min/kg bw, females: 1410 ml/min/kg bw) were higher than those of humans (males: 436 ml/min/kg bw, females: 646 ml/min/kg bw) and rats (males: 627 ml/min/kg bw, females: 679 ml/min/kg bw). The ratio of CL(OX) to CL(SC) was lowest in female mice. This finding indicated that HMF sulfo conjugation was most substantial in the liver of female mice, a target tissue for HMF-induced neoplastic effects, and that humans may be less sensitive regarding HMF sulfo conjugation compared with the rodent models. PMID:26454887

  11. Retinal Targets ALDH Positive Cancer Stem Cell and Alters the Phenotype of Highly Metastatic Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Xiaodong Mu

    2015-01-01

    Full Text Available Aldehyde dehydrogenase (ALDH is a cancer stem cell marker. Retinoic acid has antitumor properties, including the induction of apoptosis and inhibition of proliferation. Retinal, the precursor of retinoic acid, can be oxidized to retinoic acid by dehydrogenases, including ALDH. We hypothesized that retinal could potentially be transformed to retinoic acid with higher efficiency by cancer stem cells, due to the higher ALDH activity. We previously observed that ALDH activity is greater in highly metastatic K7M2 osteosarcoma (OS cells than in nonmetastatic K12 OS cells. We also demonstrated that ALDH activity correlates with clinical metastases in bone sarcoma patients, suggesting that ALDH may be a therapeutic target specific to cells with high metastatic potential. Our current results demonstrated that retinal preferentially affected the phenotypes of ALDH-high K7M2 cells in contrast to ALDH-low K12 cells, which could be mediated by the more efficient transformation of retinal to retinoic acid by ALDH in K7M2 cells. Retinal treatment of highly metastatic K7M2 cells decreased their proliferation, invasion capacity, and resistance to oxidative stress. Retinal altered the expression of metastasis-related genes. These observations indicate that retinal may be used to specifically target metastatic cancer stem cells in OS.

  12. Deficient Expression of Aldehyde Dehydrogenase 1A1 Is Consistent with Increased Sensitivity of Gorlin Syndrome Patients to Radiation Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Aaron T.; Magnaldo, Thierry; Sontag, Ryan L.; Anderson, Lindsey N.; Sadler, Natalie C.; Piehowski, Paul D.; Gache, Yannick; Weber, Thomas J.

    2015-06-01

    Human phenotypes that are highly susceptible to radiation carcinogenesis have been identified. Sensitive phenotypes often display robust regulation of molecular features that modify biological response, which can facilitate identification of relevant pathways/networks. Here we interrogate primary dermal fibroblasts isolated from Gorlin syndrome patients (GDFs), who display a pronounced tumorigenic response to radiation, in comparison to normal human dermal fibroblasts (NHDFs). Our approach exploits newly developed thiol-reactive probes with a flexible click chemistry functional group to define changes in protein thiol profiles in live cell studies, which minimizes artifacts associated with cell lysis. We observe qualitative differences in protein thiol profiles by SDS-PAGE analysis when detection by iodoacetamide vs maleimide probe chemistries are compared, and pretreatment of cells with hydrogen peroxide eliminates detection of the majority of SDS-PAGE bands. Redox probes revealed deficient expression of an apparent 55 kDa protein thiol in GDFs from independent donors, compared with NHDFs. Proteomics tentatively identified this protein as aldehyde dehydrogenase 1A1 (ALDH1A1), a key enzyme regulating retinoic acid synthesis, and this deficiency was confirmed by Western blot. Redox probes revealed additional protein thiol differences between GDFs and NHDFs, including radiation responsive annexin family members. Our results indicate a multifactorial basis for the unusual sensitivity of Gorlin syndrome to radiation carcinogenesis, and the pathways identified have plausible implications for radiation health effects.

  13. Fatty Aldehyde and Fatty Alcohol Metabolism: Review and Importance for Epidermal Structure and Function

    OpenAIRE

    Rizzo, William B.

    2013-01-01

    Normal fatty aldehyde and alcohol metabolism is essential for epidermal differentiation and function. Long-chain aldehydes are produced by catabolism of several lipids including fatty alcohols, sphingolipids, ether glycerolipids, isoprenoid alcohols and certain aliphatic lipids that undergo α- or ω-oxidation. The fatty aldehyde generated by these pathways is chiefly metabolized to fatty acid by fatty aldehyde dehydrogenase (FALDH, alternately known as ALDH3A2), which also functions to oxidize...

  14. Separation and Purification of Betaine Aldehyde Dehydrogenase from Wild Suaeda liaotungensis

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    High active betaine aldehyde dehydrogenase (BADH, EC 1.2.1.8) is found in wild Suaeda liaotungensis. The enzyme is purified 206-fold with recovery of 1.5%. It have a specific activity of 2363 nmol/min*mg protein and the molecular mass of each subunit is 64.5 kDa as determined by SDS-PAGE.

  15. Mechanism exploration of aldehyde dehydrogenase 2 in the cardioprotection of fasudil%乙醛脱氢酶2在法舒地尔心肌保护作用中的机制

    Institute of Scientific and Technical Information of China (English)

    叶红伟; 康品方; 王洪巨; 李正红; 关宿东; 高琴

    2013-01-01

    目的 探讨乙醛脱氢酶2(ALDH2)是否参与Rho激酶抑制剂法舒地尔的心肌保护作用,并分析其可能机制.方法 采用离体大鼠心脏,结扎冠状动脉左前降支30 min模拟局部心肌缺血,松开结扎线恢复灌流120 min复制心肌缺血/再灌注(I/R)模型.实验分4组:I/R组、法舒地尔组、ALDH2抑制剂氨基氰(CYA)组和法舒地尔+CYA(联合组)组.连续记录左心室动力学变化,再灌注期间收集冠脉流出液测定乳酸脱氢酶(LDH)含量;RT-PCR检测ALDH2mRNA表达以及Bcl-2/Bax比值的变化.结果 与I/R组比,法舒地尔组明显促进了左室发展压、左心室内压最大上升和下降速率、左心室做功的恢复,降低复灌期冠脉流出液中LDH的释放,ALDH2 mRNA表达增加,Bcl-2/Bax比值增高.ALDH2抑制剂CYA明显减弱法舒地尔的作用,抑制了心室动力学指标的恢复,LDH释放增多,ALDH2mRNA表达降低,Bcl-2/Bax比值降低.结论 法舒地尔抑制Rho激酶信号通路发挥心肌保护作用,其机制可能与激动ALDH2、抑制凋亡发生有关.%Objective To investigate whether aldehyde dehydrogenase 2 (ALDH2) was involved in the cardioprotection of fasudil, the inhibitor of Rho-kinase, and explore the mechanism. Methods Hearts isolated from male SD rats were subjected to 30 minutes of re gional ischemia (occlusion of left anterior descending artery) followed by 120 minutes of reperfusion. The experiment was divided into 4 groups: I/R, Fasudil, ALDH2 inhibitor CYA and Fasudil + CYA groups. The left ventricular hemodynamics were continuous recorded, the coronary effluent was collected during the reperfusion period to determinate lactate dehydrogenase (LDH) levels. ALDH2 mRNA expression and the ratio of Bcl-2/Bax were detected by RT-PCR. Results Compared with I/R group, fasudil significantly increased the restore of left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure and rate pressure product, reduced LDH release during

  16. The use of tomato aminoaldehyde dehydrogenase 1 for the detection of aldehydes in fruit distillates.

    Science.gov (United States)

    Frömmel, Jan; Tarkowski, Petr; Kopečný, David; Šebela, Marek

    2016-09-25

    Plant NAD(+)-dependent aminoaldehyde dehydrogenases (AMADHs, EC 1.2.1.19) belong to the family 10 of aldehyde dehydrogenases. They participate in the metabolism of polyamines or osmoprotectants. The enzymes are characterized by their broad substrate specificity covering ω-aminoaldehydes, aliphatic and aromatic aldehydes as well as nitrogen-containing heterocyclic aldehydes. The isoenzyme 1 from tomato (Solanum lycopersicum; SlAMADH1) oxidizes aliphatic aldehydes very efficiently and converts also furfural, its derivatives or benzaldehyde, which are present at low concentrations in alcoholic distillates such as fruit brandy. In this work, SlAMADH1 was examined as a bioanalytical tool for their detection. These aldehydes arise from fermentation processes or thermal degradation of sugars and their presence is related to health complications after consumption including nausea, emesis, sweating, decrease in blood pressure, hangover headache, among others. Sixteen samples of slivovitz (plum brandy) from local producers in Moravia, Czech Republic, were analyzed for their aldehyde content using a spectrophotometric activity assay with SlAMADH1. In all cases, there were oxidative responses observed when monitoring NADH production in the enzymatic reaction. Aldehydes in the distillate samples were also subjected to a standard determination using reversed-phase HPLC with spectrophotometric and tandem mass spectrometric detection after a derivatization with 2,4-dinitrophenylhydrazine. Results obtained by both methods were found to correlate well for a majority of the analyzed samples. The possible applicability of SlAMADH1 for the evaluation of aldehyde content in food and beverages has now been demonstrated. PMID:26703808

  17. The effect of peroxynitrite decomposition catalyst MnTBAP on aldehyde dehydrogenase-2 nitration by organic nitrates: role in nitrate tolerance.

    Science.gov (United States)

    Mollace, Vincenzo; Muscoli, Carolina; Dagostino, Concetta; Giancotti, Luigino Antonio; Gliozzi, Micaela; Sacco, Iolanda; Visalli, Valeria; Gratteri, Santo; Palma, Ernesto; Malara, Natalia; Musolino, Vincenzo; Carresi, Cristina; Muscoli, Saverio; Vitale, Cristiana; Salvemini, Daniela; Romeo, Francesco

    2014-11-01

    Bioconversion of glyceryl trinitrate (GTN) into nitric oxide (NO) by aldehyde dehydrogenase-2 (ALDH-2) is a crucial mechanism which drives vasodilatory and antiplatelet effect of organic nitrates in vitro and in vivo. Oxidative stress generated by overproduction of free radical species, mostly superoxide anions and NO-derived peroxynitrite, has been suggested to play a pivotal role in the development of nitrate tolerance, though the mechanism still remains unclear. Here we studied the free radical-dependent impairment of ALDH-2 in platelets as well as vascular tissues undergoing organic nitrate ester tolerance and potential benefit when using the selective peroxynitrite decomposition catalyst Mn(III) tetrakis (4-Benzoic acid) porphyrin (MnTBAP). Washed human platelets were made tolerant to nitrates via incubation with GTN for 4h. This was expressed by attenuation of platelet aggregation induced by thrombin (40U/mL), an effect accompanied by GTN-related induction of cGMP levels in platelets undergoing thrombin-induced aggregation. Both effects were associated to attenuated GTN-induced nitrite formation in platelets supernatants and to prominent nitration of ALDH-2, the GTN to NO metabolizing enzyme, suggesting that GTN tolerance was associated to reduced NO formation via impairment of ALDH-2. These effects were all antagonized by co-incubation of platelets with MnTBAP, which restored GTN-induced responses in tolerant platelets. Comparable effect was found under in in vivo settings. Indeed, MnTBAP (10mg/kg, i.p.) significantly restored the hypotensive effect of bolus injection of GTN in rats made tolerants to organic nitrates via chronic administration of isosorbide-5-mononitrate (IS-5-MN), thus confirming the role of peroxynitrite overproduction in the development of tolerance to vascular responses induced by organic nitrates. In conclusion, oxidative stress subsequent to prolonged use of organic nitrates, which occurs via nitration of ALDH-2, represents a key event

  18. Genetic polymorphisms of alcohol dehydrogense-1B and aldehyde dehydrogenase-2, alcohol flushing, mean corpuscular volume, and aerodigestive tract neoplasia in Japanese drinkers.

    Science.gov (United States)

    Yokoyama, Akira; Mizukami, Takeshi; Yokoyama, Tetsuji

    2015-01-01

    Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) modulate exposure levels to ethanol/acetaldehyde. Endoscopic screening of 6,014 Japanese alcoholics yielded high detection rates of esophageal squamous cell carcinoma (SCC; 4.1%) and head and neck SCC (1.0%). The risks of upper aerodigestive tract SCC/dysplasia, especially of multiple SCC/dysplasia, were increased in a multiplicative fashion by the presence of a combination of slow-metabolizing ADH1B*1/*1 and inactive heterozygous ALDH2*1/*2 because of prolonged exposure to higher concentrations of ethanol/acetaldehyde. A questionnaire asking about current and past facial flushing after drinking a glass (≈180 mL) of beer is a reliable tool for detecting the presence of inactive ALDH2. We invented a health-risk appraisal (HRA) model including the flushing questionnaire and drinking, smoking, and dietary habits. Esophageal SCC was detected at a high rate by endoscopic mass-screening in high HRA score persons. A total of 5.0% of 4,879 alcoholics had a history of (4.0%) or newly diagnosed (1.0%) gastric cancer. Their high frequency of a history of gastric cancer is partly explained by gastrectomy being a risk factor for alcoholism because of altered ethanol metabolism, e.g., by blood ethanol level overshooting. The combination of H. pylori-associated atrophic gastritis and ALDH2*1/*2 showed the greatest risk of gastric cancer in alcoholics. High detection rates of advanced colorectal adenoma/carcinoma were found in alcoholics, 15.7% of 744 immunochemical fecal occult blood test (IFOBT)-negative alcoholics and 31.5% of the 393 IFOBT-positive alcoholics. Macrocytosis with an MCV≥106 fl increased the risk of neoplasia in the entire aerodigestive tract of alcoholics, suggesting that poor nutrition as well as ethanol/acetaldehyde exposure plays an important role in neoplasia. PMID:25427912

  19. Identification and Overexpression of a Bifunctional Aldehyde/Alcohol Dehydrogenase Responsible for Ethanol Production in Thermoanaerobacter mathranii

    DEFF Research Database (Denmark)

    Yao, Shuo; Just Mikkelsen, Marie

    2010-01-01

    Thermoanaerobacter mathranii contains four genes, adhA, adhB, bdhA and adhE, predicted to code for alcohol dehydrogenases involved in ethanol metabolism. These alcohol dehydrogenases were characterized as NADP(H)-dependent primary alcohol dehydrogenase (AdhA), secondary alcohol dehydrogenase (Adh......B), butanol dehydrogenase (BdhA) and NAD(H)-dependent bifunctional aldehyde/alcohol dehydrogenase (AdhE), respectively. Here we observed that AdhE is an important enzyme responsible for ethanol production in T. mathranii based on the constructed adh knockout strains. An adhE knockout strain fails to produce...... ethanol as a fermentation product, while other adh knockout strains showed no significant difference from the wild type. Further analysis revealed that the ΔadhE strain was defective in aldehyde dehydrogenase activity, but still maintained alcohol dehydrogenase activity. This showed that AdhE is the major...

  20. Association of ADHIB and ALDH2 gene polymorphisms with alcohol dependence: A pilot study from India

    OpenAIRE

    Vaswani Meera; Prasad Pushplata; Kapur Suman

    2009-01-01

    Abstract Functional polymorphism in the genes encoding alcohol dehydrogenase (ADH) 1B and aldehyde dehydrogenase (ALDH) 2 are considered most important among several genetic determinants of alcohol dependence, a complex disorder. There is no report on the widely studied Arg47His and Glu487Lys polymorphisms from Indian alcoholdependent populations. In this paper, we report, for the first time, allelic and genotypic frequencies of Arg47His and Glu487Lys single nucleotide polymorphisms (SNPs) in...

  1. Ethanol utilization regulatory protein: profile alignments give no evidence of origin through aldehyde and alcohol dehydrogenase gene fusion.

    OpenAIRE

    Nicholas, H B; Persson, B; Jörnvall, H; Hempel, J.

    1995-01-01

    The suggestion that the ethanol regulatory protein from Aspergillus has its evolutionary origin in a gene fusion between aldehyde and alcohol dehydrogenase genes (Hawkins AR, Lamb HK, Radford A, Moore JD, 1994, Gene 146:145-158) has been tested by profile analysis with aldehyde and alcohol dehydrogenase family profiles. We show that the degree and kind of similarity observed between these profiles and the ethanol regulatory protein sequence is that expected from random sequences of the same c...

  2. ALCOHOL AND ALDEHYDE DEHYDROGENASES CONTRIBUTE TO SEX-RELATED DIFFERENCES IN CLEARANCE OF ZOLPIDEM IN RATS

    Directory of Open Access Journals (Sweden)

    Cody J Peer

    2016-08-01

    Full Text Available Objectives:  The recommended zolpidem starting dose was lowered in females (5mg vs 10mg since side effects were more frequent and severe than those of males; the mechanism underlying sex differences in pharmacokinetics (PK is unknown.  We hypothesized that such differences were caused by known sex-related variability in alcohol dehydrogenase (ADH expression. Methods:  Male, female, and castrated male rats were administered 2.6 mg/kg zolpidem, +/- disulfiram (ADH/ALDH pathway inhibitor to compare PK changes induced by sex and gonadal hormones.  PK analyses were conducted in rat plasma and rat brain. Key findings:  Sex differences in PK were evident: females had a higher CMAX (112.4 vs 68.1 ug/L and AUC (537.8 vs 231.8 hr*ug/L than uncastrated males.  Castration induced an earlier TMAX (0.25 vs 1 hr, greater CMAX (109.1 vs 68.1 ug/L, and a corresponding AUC increase (339.7 vs 231.8 hr*ug/L.  Administration of disulfiram caused more drastic CMAX and TMAX changes in male vs female rats that mirrored the effects of castration on first-pass metabolism, suggesting that the observed PK differences may be caused by ADH/ALDH expression. Brain concentrations paralleled plasma concentrations.Conclusions:  These findings indicate that sex differences in zolpidem PK are influenced by variation in the expression of ADH/ALDH due to gonadal androgens.

  3. Aldehyde dehydrogenase-2 protects against myocardial infarction-related cardiac fibrosis through modulation of the Wnt/β-catenin signaling pathway

    Directory of Open Access Journals (Sweden)

    Zhao XJ

    2015-09-01

    Full Text Available Xinjun Zhao,1,2,* Yue Hua,1,2,* Hongmei Chen,1,2,* Haiyu Yang,3,* Tao Zhang,1,2,* Guiqiong Huang,4,* Huijie Fan,1,2 Zhangbin Tan,1,2 Xiaofang Huang,1,2 Bin Liu,5 Yingchun Zhou1,21The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangdong, Guangzhou, People’s Republic of China; 2Nanfang Hospital, Southern Medical University, Guangdong, Guangzhou, People’s Republic of China; 3Jiangmen Wuyi Traditional Chinese Medicine Hospital, Guangdong, Jiangmen, People’s Republic of China; 4Huizhou Hospital of Traditional Chinese Medicine, Huizhou, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou Medical University, Guangdong, Guangzhou, People’s Republic of China*These authors contributed equally to this workBackground: Aldehyde dehydrogenase-2 (ALDH2 has a protective effect on ischemic heart disease. Here, we examined the protective effects of ALDH2 on cardiac fibrosis through modulation of the Wnt/ß-catenin signaling pathway in a rat model of myocardial infarction (MI.Methods: Wistar rats were divided into the sham (control, MI (model, and ALDH2 activator (Alda-1 groups. After 10 days of treatment, the left ventricular (LV remodeling parameters of each animal were evaluated by echocardiography. Myocardial fibrosis was evaluated by Masson’s trichrome staining and Sirius Red staining. Expression levels of collagen types I and III and β-smooth muscle actin (α-SMA were examined. Finally, the expression and activity of ALDH2 and the levels of several Wnt-related proteins and genes, such as phospho-glycogen synthase kinase (GSK-3β, GSK-3β, β-catenin, Wnt-1, WNT1-inducible signaling-pathway protein 1, and tumor necrosis factor (TNF-α, were also analyzed.Results: After MI, the heart weight/body weight ratio, LV dimension at end diastole, and LV dimension at end systole were decreased, while the LV ejection

  4. Genetic polymorphisms of ADH2 and ALDH2 association with esophageal cancer risk in southwest China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the impact of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2)polymorphisms on esophageal cancer risk.METHODS: One hundred and ninety-one esophageal cancer patients and 198 healthy controls from Yanting County were enrolled in this study. ADH2 and ALDH2genotypes were examined by polymerase-chain-reaction with the confronting-two-pair-primer (PCR-CTPP)method. Unconditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence interval (95% CI).RESULTS: Both ,ADH2*1 allele and ,ALDH2*1/*2 allele showed an increased risk of developing esophageal cancer. The adjusted OR (95% CI) for ,ADH2*1allele compared with ,ADH2*2/*2 was 1.65 (95%CI= 1.02-2.68) and 1.67 (95% CI= 1.02-2.72) for ,ALDH2*1/*2 compared with ALDH2*1/*1. A significant interaction between ,ALDH2 and drinking was detected regarding esophageal cancer risk, the OR was 1.83(95% CI = 1.13-2.95). Furthermore, when compared with ADH2*2/*2 and ALDH2*1/*1 carriers, ADH2*1 and ALDH2*2 carriers showed an elevated risk of developing esophageal cancer among non-alcohol drinkers (OR =2.46, 95% CI= 0.98-6.14), and a significantly elevated risk of developing esophageal cancer among alcohol drinkers among alcohol drinkers (OR = 9.86, 95% CI=3.10-31.38).CONCLUSION: ADH2 and ALDH2 genotypes are associated with esophageal cancer risk. ADH2*1 allele and ALDH2*2 allele carriers have a much higher risk of developing esophageal cancer, especially among alcohol drinkers.

  5. The association of ADH and ALDH gene variants with alcohol drinking habits and cardiovascular disease risk factors

    DEFF Research Database (Denmark)

    Husemoen, Lise Lotte Nystrup; Fenger, Mogens; Friedrich, Nele;

    2008-01-01

    . In a Caucasian population, we examined the association of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genetic variants with alcohol drinking habits, biomarkers of alcohol exposure, and risk factors for cardiovascular disease. METHODS: The study population consisted of 1,216 Danish men and women......-MCV), and lipids]. ADH and ALDH gene variants were determined by standard techniques. Data were analyzed by regression analyses adjusted for relevant confounders. RESULTS: Self-reported alcohol drinking was significantly associated with increasing levels of ALAT, E-MCV, high-density lipoprotein cholesterol...

  6. Blood ALDH1 and GST activity in diabetes type 2 and its correlation with glycated hemoglobin.

    Science.gov (United States)

    Giebułtowicz, J; Sołobodowska, S; Bobilewicz, D; Wroczyński, P

    2014-01-01

    There is increasing evidence that oxidative stress (OS) plays a major role in the pathogenesis of diabetes mellitus (DM) and the development of its complications. As one of the consequences of OS is increased lipid peroxidation (LP), the aim of our studies was to check, how the activity of 2 enzymes involved in the detoxification of aldehydes formed during LP, glutathione S-transferase (GST) and aldehyde dehydrogenase 1 (ALDH 1) is changed in patients suffering from DM.GST and ALDH1A1 activities were determined in whole blood samples of DM type 2 patients (n=64) and healthy controls (n=60) using spectrophotometer (for GST activity) and fluorometer (for ALDH1 activity) and they were found to be significantly increased in diabetics when compared with healthy control (p<0.05). Intriguingly, grouping the DM patients on the basis of the glucose level and HbA1c revealed unusually low ALDH activity in the group of patients (n=16) with a relatively high level of these 2 parameters.The increase of ALDH1A1 and GST activity in DM seems to be associated with the severity of the disease and might be a compensatory effect against oxidative stress. Surprisingly low ALDH activity in DM patients with relatively high glucose and HbA1c levels can be a factor predisposing to the development of diabetic complications.

  7. The Immunohistochemical Assessment of ALDH1 Activity in Breast Cancer and it’s Correlation With Pathologic Features

    Directory of Open Access Journals (Sweden)

    Molanae S

    2011-12-01

    Full Text Available Background: Aldehyde dehydrogenase 1 (ALDH1 is a marker of normal and malignant human mammary stem cells that has been reported to be associated with poor prognosis. Studies on the detection of ALDH1+ cells can help the treatment of patients with breast cancer. The aim of this study was to determine the activity of ALDH1 in breast cancer and its relationship with the pathological features of the tumors.Methods: ALDH1 activity was studied by immunohistochemistry in 121 paraffin-embedded histological samples of breast cancer patients from Department of Pathology of Milad Hospital, Tehran, Iran during 2006-2007. The relationship of ALDH1 with the pathological features of the tumors (size, grade, lymph node metastasis and vascular invasion was also investigated.Results: Eighty-five percent of breast cancer samples expressed ALDH1 in their cytoplasm with a wide range of intensity (weak, moderate and strong, while 18 samples (14.9% were completely negative. The majority of cases (97.1% showed ALDH1 positivity in the stroma of tumors which varied from weak (2.9% to strong (73.5%. ALDH1 H-score (ALDH1% × intensity of tumor cells varied from 0 to 240 (mean= 80. ALDH1 H-score was ≤80 in 62 (51.2% and >80 in 59 (48.8% samples. There was no statistically significant relationship between ALDH1 H-score and age (P=0.358, tumor size (P=0.375, tumor grade (P=0.207, lymph node metastasis (P=0.125 or vascular invasion (P=0.190.Conclusion: ALDH1 activity was demonstrated in 85.1% of breast cancer samples although its level of expression was not correlated with the pathologic features of breast tumors.

  8. Variations in ADH and ALDH in Southwest California Indians

    Science.gov (United States)

    Ehlers, Cindy L.

    2007-01-01

    Native Americans as a group have the highest rates of alcohol-related deaths of all ethnicities in the United States; however, it remains unclear how and why a greater proportion of individuals in some Native American communities develop alcohol-related problems and alcohol use disorders (AUDs). One potential factor that can influence responses to alcohol are variations in alcohol-metabolizing enzymes. Researchers have analyzed the frequencies of variants in the alcohol-metabolizing enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in some Native American populations. So far the studies have yielded no evidence that an ALDH2 variant, which has shown protective effects in other populations, is found in either American Indians or Alaska Natives. A variant of the ALDH1 enzyme that is encoded by the ALDH1A1*2 allele, however, was found in a small proportion of a group of Southwest California Indians and had a protective effect against alcoholism in that population. Furthermore, a variant of the ADH1B enzyme that is encoded by the ADH1B*3 allele was found in a similar proportion of Southwest California Indians and also was associated with a protective effect. However, these findings do not explain the high prevalence of alcoholism in the tribes investigated. PMID:17718395

  9. Expression of betaine aldehyde dehydrogenase gene and salinity tolerance in rice transgenic plants

    Institute of Scientific and Technical Information of China (English)

    郭岩; 张莉; 肖岗; 曹守云; 谷冬梅; 田文忠; 陈受宜

    1997-01-01

    Betaine as one of osmolytes plays an important role in osmoregulation of most high plants. Betaine aldehyde dehydrogenase C BADH) is the second enzyme involved in betaine biosynthesis. The BADH gene from a halophite, Atriplex hortensis, was transformed into rice cultivars by bombarment method. Totally 192 transgenic rice plants were obtained and most of them had higher salt tolerance than controls. Among transgenic plants transplanted in the saline pool containing 0.5% NaCl in a greenhouse, 22 survived, 13 of which set seeds, and the frequency of seed setting was very low, only 10% . But the controls could not grow under the same condition. The results of BADH ac-tivity assay and Northern blot showed that the BADH gene was integrated into chromosomes of transgenic plants and expressed.

  10. 乙醛脱氢酶2在糖尿病大鼠心肌缺血/再灌注损伤中的抗凋亡作用%Anti-apoptotic role of mitochondrial aldehyde dehydrogenase 2 in myocardial ischemia/reperfusion injury in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    王洪巨; 康品方; 叶红伟; 于影; 王晓梅; 高琴

    2012-01-01

    目的 观察乙醛脱氢酶2(ALDH2)在糖尿病大鼠心肌缺血/再灌注凋亡发生中的作用.方法 大鼠分为正常组、糖尿病组和ALDH2激动剂乙醇+糖尿病组.4周后行离体心肌缺血/再灌注(I/R).测定复灌期间冠脉流出液中乳酸脱氢酶(LDH)含量.检测心肌组织细胞ALDH2、caspase-3的活性;RT-PCR测定左心室前壁心尖组织Bcl-2、Bax mRNA的表达.结果 与正常大鼠I/R相比,糖尿病大鼠复灌期冠脉流出液中LDH释放增加,心肌组织caspase-3活性增加,ALDH2活性降低,Bcl-2/Bax mRNA比值降低;与糖尿病大鼠心肌I/R相比,ALDH2激动剂乙醇使得心肌复灌期间冠脉流出液中LDH释放减少,心肌caspase,-3活性降低,ALDH2活性增高,Bcl-2/Bax mRNA比值增高.结论 增强ALDH2在糖尿病大鼠心肌中的表达对缺血/再灌注损伤有明显的保护作用;其机制可能与抑制细胞凋亡的发生有关.%Objective To evaluate the anti-apoptotic effect of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/ reperfusion (I/R) injury in diabetic rats. Methods Normal male SD rats were divided into normal, diabetes and ethanol (the agonist of ALDH2) + diabetes groups. In the latter two groups, diabetes was induced by an intraperitoneal injection of 55 mg/kg STZ. Four weeks after the modeling, myocardial I/R was mimicked ex vivo, and lactate dehydrogenase (LDH) content in the coronary flow was determined. The activities of caspase-3 and ALDH2 were evaluated, and the expressions of Bd-2 and Bax mRNA in the left anterior myocardium were detected using RT-PCR. Results In diabetic group, LDH release and caspase-3 activity were increased, while ALDH2 activity and Bd-2/Bax mRNA expression were decreased as compared to those in normal control group. Compared with the diabetic group, ALDH2 agonist ethanol significantly reduced LDH release and caspase-3 activity, increased ALDH2 activity and Bd-2/Bax mRNA expression. Condusion In diabetic rats, enhanced ALDH2 expression

  11. Mutations in ALDH1A3 represent a frequent cause of microphthalmia/anophthalmia in consanguineous families.

    Science.gov (United States)

    Abouzeid, Hana; Favez, Tatiana; Schmid, Angélique; Agosti, Céline; Youssef, Mohammed; Marzouk, Iman; El Shakankiry, Nihal; Bayoumi, Nader; Munier, Francis L; Schorderet, Daniel F

    2014-08-01

    Anophthalmia or microphthalmia (A/M), characterized by absent or small eye, can be unilateral or bilateral and represent developmental anomalies due to the mutations in several genes. Recently, mutations in aldehyde dehydrogenase family 1, member A3 (ALDH1A3) also known as retinaldehyde dehydrogenase 3, have been reported to cause A/M. Here, we screened a cohort of 75 patients with A/M and showed that mutations in ALDH1A3 occurred in six families. Based on this series, we estimate that mutations in ALDH1A3 represent a major cause of A/M in consanguineous families, and may be responsible for approximately 10% of the cases. Screening of this gene should be performed in a first line of investigation, together with SOX2.

  12. Sjögren-Larsson syndrome. Deficient activity of the fatty aldehyde dehydrogenase component of fatty alcohol:NAD+ oxidoreductase in cultured fibroblasts.

    OpenAIRE

    Rizzo, W B; Craft, D A

    1991-01-01

    Sjögren-Larsson syndrome (SLS) is an inherited disorder associated with impaired fatty alcohol oxidation due to deficient activity of fatty alcohol:NAD+ oxidoreductase (FAO). FAO is a complex enzyme which consists of two separate proteins that sequentially catalyze the oxidation of fatty alcohol to fatty aldehyde and fatty acid. To determine which enzymatic component of FAO was deficient in SLS, we assayed fatty aldehyde dehydrogenase (FALDH) and fatty alcohol dehydrogenase in cultured fibrob...

  13. ALDH expression characterizes G1-phase proliferating beta cells during pregnancy.

    Directory of Open Access Journals (Sweden)

    Lijuan Zhang

    Full Text Available High levels of aldehyde dehydrogenase (ALDH activity have been detected in various progenitor and stem cells. Thus, Aldefluor fluorescence, which represents precisely the ALDH activity, has been widely used for the identification, evaluation, and isolation of stem and progenitor cells. Recently, ALDH activity was detected in embryonic and adult mouse pancreas, specifically in adult centroacinar and terminal duct cells supposed to harbor endocrine and exocrine progenitor cells in the adult pancreas. Nevertheless, ALDH activity and aldeflour fluorescence have not been examined in beta cells. Here, we report a dynamic increase in the number of aldeflour+ beta cells during pregnancy. Interestingly, nearly all these aldeflour+ beta cells are positive for Ki-67, suggesting that they are in an active cell cycle (G1, S and M phases. To determine precisely at which phase beta cells activate ALDH activity and thus become aldeflour+, we co-stained insulin with additional proliferation markers, phosphohistone3 (PHH3, a marker for M-phase proliferating cells and Bromodeoxyuridine (BrdU, a marker for S-phase proliferating cells. Our data show little aldeflour+ beta cells that were positive for either PHH3, or BrdU, suggesting that beta cells activate ALDH and become Aldefluor+ when they enter G1-phase of active cell cycle, but may downregulate ALDH when they leave G1-phase and enter S phase. Our data thus reveal a potential change in ALDH activity of proliferating beta cells during pregnancy, which provides a novel method for isolation and analysis of proliferating beta cells. Moreover, our data also suggest that caution needs to be taken on interpretation of Aldefluor lineage-tracing data in pancreas.

  14. ALDH Expression Characterizes G1-Phase Proliferating Beta Cells during Pregnancy

    Science.gov (United States)

    Zhang, Lijuan; Wang, Lin; Liu, Xiaoliang; Zheng, Dongming; Liu, Sishi; Liu, Caixia

    2014-01-01

    High levels of aldehyde dehydrogenase (ALDH) activity have been detected in various progenitor and stem cells. Thus, Aldefluor fluorescence, which represents precisely the ALDH activity, has been widely used for the identification, evaluation, and isolation of stem and progenitor cells. Recently, ALDH activity was detected in embryonic and adult mouse pancreas, specifically in adult centroacinar and terminal duct cells supposed to harbor endocrine and exocrine progenitor cells in the adult pancreas. Nevertheless, ALDH activity and aldeflour fluorescence have not been examined in beta cells. Here, we report a dynamic increase in the number of aldeflour+ beta cells during pregnancy. Interestingly, nearly all these aldeflour+ beta cells are positive for Ki-67, suggesting that they are in an active cell cycle (G1, S and M phases). To determine precisely at which phase beta cells activate ALDH activity and thus become aldeflour+, we co-stained insulin with additional proliferation markers, phosphohistone3 (PHH3, a marker for M-phase proliferating cells) and Bromodeoxyuridine (BrdU, a marker for S-phase proliferating cells). Our data show little aldeflour+ beta cells that were positive for either PHH3, or BrdU, suggesting that beta cells activate ALDH and become Aldefluor+ when they enter G1-phase of active cell cycle, but may downregulate ALDH when they leave G1-phase and enter S phase. Our data thus reveal a potential change in ALDH activity of proliferating beta cells during pregnancy, which provides a novel method for isolation and analysis of proliferating beta cells. Moreover, our data also suggest that caution needs to be taken on interpretation of Aldefluor lineage-tracing data in pancreas. PMID:24787690

  15. Effects of ALDH2∗2 on alcohol problem trajectories of Asian American college students.

    Science.gov (United States)

    Luczak, Susan E; Yarnell, Lisa M; Prescott, Carol A; Myers, Mark G; Liang, Tiebing; Wall, Tamara L

    2014-02-01

    The variant aldehyde dehydrogenase allele, ALDH2∗2, consistently has been associated with protection against alcohol dependence, but the mechanism underlying this process is not known. This study examined growth trajectories of alcohol consumption (frequency, average quantity, binge drinking, maximum drinks) and problems over the college years and then tested whether the ALDH2 genotype mediated or moderated the relationship between alcohol consumption and problems. Asian American college students (N = 433) reported on their drinking behavior in their first year of college and then annually for 3 consecutive years. Alcohol consumption and problems increased over the college years for both those with and without ALDH2∗2, but having an ALDH2∗2 allele was associated with less of an increase in problems over time. A mediation model was supported, with ALDH2∗2 group differences in problems fully accounted for by differences in frequency of binge drinking. Findings also supported a moderation hypothesis: All four alcohol consumption variables were significant predictors of subsequent alcohol problems, but these relationships were not as strong in those with ALDH2∗2 as in those without ALDH2∗2. Our findings suggest that the interplay between ALDH2∗2 and drinking-related problems is complex, involving both mediation and moderation processes that reduce the likelihood of developing problems via reduction of heavy drinking as well as by altering the relationship between alcohol consumption and problems. Results of this longitudinal study provide evidence that what seems like a relatively straightforward effect of a diminished ability to metabolize alcohol on drinking behavior is actually dependent on behavior and developmental stage. PMID:24661165

  16. Changes of aldehyde dehydrogenase 2 on myocardial injury in diabetic rats%乙醛脱氢酶2在糖尿病大鼠致心肌损伤中的变化

    Institute of Scientific and Technical Information of China (English)

    史晓俊; 康品方; 高琴; 叶红伟; 李正红; 汤阳; 王洪巨

    2014-01-01

    目的:观察线粒体乙醛脱氢酶2 (aldehyde dehydrogenase 2,ALDH2)在糖尿病大鼠不同阶段导致心肌损伤中的变化,并分析其可能机制.方法:采用链脲佐菌素(streptozotocin,STZ)55 mg/kg腹腔注射复制糖尿病大鼠模型,造模成功后分别于4、8、12周时行离体心脏灌流,测定血流动力学指标;采用酶联免疫吸附实验(ELISA)检测血浆白细胞介素1(IL-1)、白细胞介素4(IL-4)水平及心肌组织4-羟壬烯醛(4-hydroxynonenal,4-HNE)含量;测定心肌组织ALDH2活性;RT-PCR测定心肌组织Bax、Bcl-2 mRNA的表达.结果:与对照组相比,糖尿病组左室发展压(left ventricular developed pressure,LVDP)、心率(HR)和左室做功(rate pressure product,RPP)明显降低(P<0.05或P<0.01),血浆IL-1水平增加(P<0.01),IL-4水平降低(P<0.01),心肌组织ALDH2活性下降(P<0.01),4-HNE含量增加(P<0.01);Bcl-2/Bax mRNA比值降低(P<0.01);随着糖尿病病程的延长,LVDP、HR和RPP进一步降低(P<0.01),血浆IL-4水平降低(P<0.05或P<0.01),IL-1水平增加,心肌组织ALDH2活性进一步降低(P<0.01),心肌组织4-HNE明显增加(P<0.01)、而Bcl-2/Bax mRNA比值降低(P<0.05或P<0.01).结论:随着糖尿病病程的延长,炎性损伤逐渐加重,凋亡增加,其机制可能与心肌ALDH2活性逐渐降低有关.%AIM:To investigate the changes of aldehyde dehydrogenase 2 (ALDH2) on myocardial injury in different stages of diabetic rats and analyze the related mechanism.METHODS:Diabetic (DM) model in SD rat was induced by a single intraperitoneal injection of 55 mg/kg streptozoticin (STZ).DM rats were divided into fourth week (DM4W),eighth week (DM8W) and twelfth week (DM12W) groups.The ventricular hemodynamic parameters were recorded,plasma interleukin-1 (IL-1),interleukin-4 (IL-4) and cardiac 4-hydroxynon-2-enal (4-HNE) levels were determined by enzyme-linked immuno sorbent assay (ELISA),cardiac ALDH2 activity was measured.The expressions of Bax and Bcl-2 at

  17. Xanthine dehydrogenase and aldehyde oxidase impact plant hormone homeostasis and affect fruit size in 'Hass' avocado.

    Science.gov (United States)

    Taylor, Nicky J; Cowan, A Keith

    2004-04-01

    The contribution of xanthine dehydrogenase (XDH, EC 1.1.1.204) to fruit size was investigated using the normal and small-fruit variants of Persea americana Mill. cv. 'Hass'. Inhibition of XDH by treatment of normal fruit, in the linear phase of growth (phase II), with allopurinol (Allo) arrested fruit growth. Adenine (Ade), a less effective inhibitor of this enzyme, also arrested fruit growth when applied in phase II and slowed fruit growth when applied in phase III. A time-course study on the activity of XDH in mesocarp tissue from normal and small fruit showed that maximum activity occurred late in phase II and that the peak in activity was absent in mesocarp of the small fruit. Feeding Ade to growing fruit in phase III caused a transient decline in fruit growth (measured as change in fruit length). Thereafter, growth resumed although fruit size was irreversibly affected. Treatment of fruit with Ade and Ade-containing cytokinins altered activity of another molybdenum enzyme, aldehyde oxidase (EC 1.2.3.1). Cytokinin oxidase was induced by cytokinin and auxin. Purine catabolism via hypoxanthine/xanthine was operative in normal fruit and in mesocarp from the small-fruit variant and as expected, Allo treatment caused accumulation of xanthine and adenine. In the absence of an increase in XDH during growth of the small-fruit phenotype, low levels of Ade were interpreted as resulting from respiration-enhanced adenylate depletion. Stress and/or pathogen induction of the alternative oxidase pathway is proposed as a possible cause.

  18. ALDH2 genotype has no effect on salivary acetaldehyde without the presence of ethanol in the systemic circulation.

    Directory of Open Access Journals (Sweden)

    Andreas Helminen

    Full Text Available BACKGROUND: Acetaldehyde associated with alcoholic beverages was recently classified as carcinogenic (Group 1 to humans based on uniform epidemiological and biochemical evidence. ALDH2 (aldehyde dehydrogenase 2 deficient alcohol consumers are exposed to high concentrations of salivary acetaldehyde and have an increased risk of upper digestive tract cancer. However, this interaction is not seen among ALDH2 deficient non-drinkers or rare drinkers, regardless of their smoking status or consumption of edibles containing ethanol or acetaldehyde. Therefore, the aim of this study was to examine the effect of the ALDH2 genotype on the exposure to locally formed acetaldehyde via the saliva without ethanol ingestion. METHODS: The ALDH2 genotypes of 17 subjects were determined by PCR-RFLP. The subjects rinsed out their mouths with 5 ml of 40 vol% alcohol for 5 seconds. Salivary ethanol and acetaldehyde levels were measured by gas chromatography. RESULTS: Acetaldehyde reached mutagenic levels rapidly and the exposure continued for up to 20 minutes. The mean salivary acetaldehyde concentrations did not differ between ALDH2 genotypes. CONCLUSIONS: For ALDH2 deficient subjects, an elevated exposure to endogenously formed acetaldehyde requires the presence of ethanol in the systemic circulation. IMPACT: Our findings provide a logical explanation for how there is an increased incidence of upper digestive tract cancers among ALDH2 deficient alcohol drinkers, but not among those ALDH2 deficient subjects who are locally exposed to acetaldehyde without bloodborne ethanol being delivered to the saliva. Thus, ALDH2 deficient alcohol drinkers provide a human model for increased local exposure to acetaldehyde derived from the salivary glands.

  19. Expression of aldehyde dehydrogenase after neoadjuvant chemotherapy is associated with expression of hypoxia-inducible factors 1 and 2 alpha and predicts prognosis in locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Daniel Guimarães Tiezzi

    2013-05-01

    Full Text Available OBJECTIVE: To analyze the expression of hypoxia-inducible factors (hypoxia-inducible factor 1A and hypoxia-inducible factor 2A and aldehyde dehydrogenase proteins in patients with locally advanced breast carcinoma who were subjected to neoadjuvant chemotherapy. METHODS: We included 90 patients with histologically confirmed stage II and III breast carcinoma who were treated with neoadjuvant chemotherapy between 2000 and 2005. Immunohistochemistry for aldehyde dehydrogenase, hypoxia-inducible factor 1A, and hypoxia-inducible factor 2A was performed before and after neoadjuvant chemotherapy. We analyzed the influence of clinical and pathological features on clinical and pathological response, disease-free survival, and overall survival. RESULTS: An objective clinical response to neoadjuvant chemotherapy was observed in 80% of patients, with 12% showing a complete pathological response. Among all clinical and pathological parameters, only the expression of hypoxia-inducible factor 1A was associated with a pathological response. A positive association was found between expression of aldehyde dehydrogenase and that of hypoxia-inducible factor 1A before and after chemotherapy. Aldehyde dehydrogenase expression was associated with expression of hypoxia inducible-factor 2A in tumors after neoadjuvant treatment. In a univariate analysis, prognosis was influenced by age, pathological response, metastasis to axillary lymph nodes after neoadjuvant chemotherapy, overexpression of hypoxia-inducible factor 2, and the presence of aldehyde dehydrogenase-positive cells within the primary tumor after neoadjuvant chemotherapy. In a multivariate analysis, only age and the presence of aldehyde dehydrogenase-positive cells after chemotherapy were associated with reduced overall survival. CONCLUSION: The presence of aldehyde dehydrogenase-positive cells within the residual tumor after neoadjuvant chemotherapy is associated with an increase in the expression of hypoxia

  20. Loss of aldehyde dehydrogenase in an Escherichia coli mutant selected for growth on the rare sugar L-galactose.

    OpenAIRE

    Zhu, Y; Lin, E C

    1987-01-01

    Escherichia coli K-12 converts L-fucose to dihydroxyacetone phosphate (C-1 to C-3) and L-lactaldehyde (C-4 to C-6) by a pathway specified by the fuc regulon. Aerobically, L-lactaldehyde serves as a carbon and energy source by the action of an aldehyde dehydrogenase of broad specificity; the product, L-lactate, is then converted to pyruvate. Anaerobically, L-lactaldehyde serves as an electron acceptor to regenerate NAD from NADH by the action of an oxidoreductase; the reduced product, L-12-pro...

  1. NAD-linked aldehyde dehydrogenase for aerobic utilization of L-fucose and L-rhamnose by Escherichia coli.

    OpenAIRE

    Y.M. Chen; Zhu, Y; Lin, E C

    1987-01-01

    Mutant analysis revealed that complete utilization of L-fucose and L-rhamnose by Escherichia coli requires the activity of a common NAD-linked aldehyde dehydrogenase which converts L-lactaldehyde to L-lactate. Mutations affecting this activity mapped to the ald locus at min 31, well apart from the fuc genes (min 60) encoding the trunk pathway for L-fucose dissimilation (as well as L-1,2-propanediol oxidoreductase) and the rha genes (min 88) encoding the trunk pathway for L-rhamnose dissimilat...

  2. Molecular cloning of a plant betaine-aldehyde dehydrogenase, an enzyme implicated in adaptation to salinity and drought.

    OpenAIRE

    Weretilnyk, E A; Hanson, A D

    1990-01-01

    Many plants, as well as other organisms, accumulate betaine (N,N,N-trimethylglycine) as a nontoxic or protective osmolyte under saline or dry conditions. In plants, the last step in betaine synthesis is catalyzed by betaine-aldehyde dehydrogenase (BADH, EC 1.2.1.8), a nuclear-encoded chloroplastic enzyme. A cDNA clone for BADH (1812 base pairs) was selected from a lambda gt10 cDNA library derived from leaves of salt-stressed spinach (Spinacia oleracea L.). The library was screened with oligon...

  3. ALDH1A3 mutations cause recessive anophthalmia and microphthalmia.

    Science.gov (United States)

    Fares-Taie, Lucas; Gerber, Sylvie; Chassaing, Nicolas; Clayton-Smith, Jill; Hanein, Sylvain; Silva, Eduardo; Serey, Margaux; Serre, Valérie; Gérard, Xavier; Baumann, Clarisse; Plessis, Ghislaine; Demeer, Bénédicte; Brétillon, Lionel; Bole, Christine; Nitschke, Patrick; Munnich, Arnold; Lyonnet, Stanislas; Calvas, Patrick; Kaplan, Josseline; Ragge, Nicola; Rozet, Jean-Michel

    2013-02-01

    Anophthalmia and microphthalmia (A/M) are early-eye-development anomalies resulting in absent or small ocular globes, respectively. A/M anomalies occur in syndromic or nonsyndromic forms. They are genetically heterogeneous, some mutations in some genes being responsible for both anophthalmia and microphthalmia. Using a combination of homozygosity mapping, exome sequencing, and Sanger sequencing, we identified homozygosity for one splice-site and two missense mutations in the gene encoding the A3 isoform of the aldehyde dehydrogenase 1 (ALDH1A3) in three consanguineous families segregating A/M with occasional orbital cystic, neurological, and cardiac anomalies. ALDH1A3 is a key enzyme in the formation of a retinoic acid gradient along the dorso-ventral axis during early eye development. Transitory expression of mutant ALDH1A3 open reading frames showed that both missense mutations reduce the accumulation of the enzyme, potentially leading to altered retinoic acid synthesis. Although the role of retinoic acid signaling in eye development is well established, our findings provide genetic evidence of a direct link between retinoic-acid-synthesis dysfunction and early-eye-development anomalies in humans.

  4. ALDH1A1 maintains ovarian cancer stem cell-like properties by altered regulation of cell cycle checkpoint and DNA repair network signaling.

    Directory of Open Access Journals (Sweden)

    Erhong Meng

    Full Text Available OBJECTIVE: Aldehyde dehydrogenase (ALDH expressing cells have been characterized as possessing stem cell-like properties. We evaluated ALDH+ ovarian cancer stem cell-like properties and their role in platinum resistance. METHODS: Isogenic ovarian cancer cell lines for platinum sensitivity (A2780 and platinum resistant (A2780/CP70 as well as ascites from ovarian cancer patients were analyzed for ALDH+ by flow cytometry to determine its association to platinum resistance, recurrence and survival. A stable shRNA knockdown model for ALDH1A1 was utilized to determine its effect on cancer stem cell-like properties, cell cycle checkpoints, and DNA repair mediators. RESULTS: ALDH status directly correlated to platinum resistance in primary ovarian cancer samples obtained from ascites. Patients with ALDHHIGH displayed significantly lower progression free survival than the patients with ALDHLOW cells (9 vs. 3 months, respectively p<0.01. ALDH1A1-knockdown significantly attenuated clonogenic potential, PARP-1 protein levels, and reversed inherent platinum resistance. ALDH1A1-knockdown resulted in dramatic decrease of KLF4 and p21 protein levels thereby leading to S and G2 phase accumulation of cells. Increases in S and G2 cells demonstrated increased expression of replication stress associated Fanconi Anemia DNA repair proteins (FANCD2, FANCJ and replication checkpoint (pS317 Chk1 were affected. ALDH1A1-knockdown induced DNA damage, evidenced by robust induction of γ-H2AX and BAX mediated apoptosis, with significant increases in BRCA1 expression, suggesting ALDH1A1-dependent regulation of cell cycle checkpoints and DNA repair networks in ovarian cancer stem-like cells. CONCLUSION: This data suggests that ovarian cancer cells expressing ALDH1A1 may maintain platinum resistance by altered regulation of cell cycle checkpoint and DNA repair network signaling.

  5. Molecular cloning of a plant betaine-aldehyde dehydrogenase, an enzyme implicated in adaptation to salinity and drought

    International Nuclear Information System (INIS)

    Many plants, as well as other organisms, accumulate betaine (N,N,N-trimethylglycine) as a nontoxic or protective osmolyte under saline or dry conditions. In plants, the last step in betaine synthesis is catalyzed by betaine-aldehyde dehydrogenase, a nuclear-encoded chloroplastic enzyme. A cDNA clone for BADH (1812 base pairs) was selected from a λgt10 cDNA library derived from leaves of salt-stressed spinach (Spinacia oleracea L.). The library was screened with oligonucleotide probes corresponding to amino acid sequences of two peptides prepared from purified BADH. The authenticity of the clone was confirmed by nucleotide sequence analysis; this analysis demonstrated the presence of a 1491-base-pair open reading frame that contained sequences encoding 12 peptide fragments of BADH. The clone hybridized to a 1.9-kilobase mRNA from spinach leaves; this mRNA was more abundant in salt-stressed plants, consistent with the known salt induction of BADH activity. The amino acid sequence deduced for the BADH cDNA sequence showed substantial similarities to those for nonspecific aldehyde dehydrogenases from several sources, including absolute conservation of a decapeptide in the probable active site. Comparison of deduced and determined amino acid sequences indicated that the transit peptide may comprise only 7 or 8 residues, which is atypically short for precursors to stromal proteins

  6. Molecular cloning of a plant betaine-aldehyde dehydrogenase, an enzyme implicated in adaptation to salinity and drought.

    Science.gov (United States)

    Weretilnyk, E A; Hanson, A D

    1990-04-01

    Many plants, as well as other organisms, accumulate betaine (N,N,N-trimethylglycine) as a nontoxic or protective osmolyte under saline or dry conditions. In plants, the last step in betaine synthesis is catalyzed by betaine-aldehyde dehydrogenase (BADH, EC 1.2.1.8), a nuclear-encoded chloroplastic enzyme. A cDNA clone for BADH (1812 base pairs) was selected from a lambda gt10 cDNA library derived from leaves of salt-stressed spinach (Spinacia oleracea L.). The library was screened with oligonucleotide probes corresponding to amino acid sequences of two peptides prepared from purified BADH. The authenticity of the clone was confirmed by nucleotide sequence analysis; this analysis demonstrated the presence of a 1491-base-pair open reading frame that contained sequences encoding 12 peptide fragments of BADH. The clone hybridized to a 1.9-kilobase mRNA from spinach leaves; this mRNA was more abundant in salt-stressed plants, consistent with the known salt induction of BADH activity. The amino acid sequence deduced from the BADH cDNA sequence showed substantial similarities to those for nonspecific aldehyde dehydrogenases (EC 1.2.1.3 and EC 1.2.1.5) from several sources, including absolute conservation of a decapeptide in the probable active site. Comparison of deduced and determined amino acid sequences indicated that the transit peptide may comprise only 7 or 8 residues, which is atypically short for precursors to stromal proteins. PMID:2320587

  7. Inhibition of ALDH1A1 activity decreases expression of drug transporters and reduces chemotherapy resistance in ovarian cancer cell lines.

    Science.gov (United States)

    Januchowski, Radosław; Wojtowicz, Karolina; Sterzyńska, Karolina; Sosińska, Patrycja; Andrzejewska, Małgorzata; Zawierucha, Piotr; Nowicki, Michał; Zabel, Maciej

    2016-09-01

    The high mortality of ovarian cancer patients results from the failure of treatment caused by the inherent or acquired chemotherapy drug resistance. It was reported that overexpression of aldehyde dehydrogenase A1 (ALDH1A1) in cancer cells can be responsible for the development of drug resistance. To add the high expression of the drug transporter proteins the ALDHA1 is considered as a molecular target in cancer therapy. Therefore, we analysed drug-resistant ovarian cancer cell lines according to ALDHA1 expression and the association with drug resistance. The expression of ALDH1A1, P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) was determined using a microarray and confirmed by Q-PCR, western blot and fluorescence analysis. ALDH1A1 activity was determined using an Aldefluor assay. The impact of all-trans retinoic acid (ATRA) and diethylaminobenzaldehyde (DEAB) on chemotherapy resistance was assessed by the MTT chemosensitivity assay. The most abundant expression of ALDH1A1 was noted in paclitaxel- and topotecan-resistant cell lines where two populations of ALDH-positive and ALDH-negative cells could be observed. Those cell lines also revealed the overexpression of P-gp and BCRP respectively, and were able to form spheres in non-adherent conditions. Pre-treatment with ATRA and DEAB reduced chemotherapy resistance in both cell lines. ATRA treatment led to downregulation of the ALDH1A1, P-gp and BCRP proteins. DEAB treatment led to downregulation of the P-gp protein and BCRP transcript and protein. Our results indicate that ALDH1A1-positive cancer cells can be responsible for drug resistance development in ovarian cancer. Developing more specific ALDH1A1 inhibitors can increase chemotherapy effectiveness in ovarian cancer.

  8. The bifunctional aldehyde-alcohol dehydrogenase controls ethanol and acetate production in Entamoeba histolytica under aerobic conditions.

    Science.gov (United States)

    Pineda, Erika; Encalada, Rusely; Olivos-García, Alfonso; Néquiz, Mario; Moreno-Sánchez, Rafael; Saavedra, Emma

    2013-01-16

    By applying metabolic control analysis and inhibitor titration we determined the degree of control (flux control coefficient) of pyruvate:ferredoxin oxidoreductase (PFOR) and bifunctional aldehyde-alcohol dehydrogenase (ADHE) over the fluxes of fermentative glycolysis of Entamoeba histolytica subjected to aerobic conditions. The flux-control coefficients towards ethanol and acetate formation determined for PFOR titrated with diphenyleneiodonium were 0.07 and 0.09, whereas for ADHE titrated with disulfiram were 0.33 and -0.19, respectively. ADHE inhibition induced significant accumulation of glycolytic intermediates and lower ATP content. These results indicate that ADHE exerts significant flux-control on the carbon end-product formation of amoebas subjected to aerobic conditions. PMID:23201265

  9. Association and ancestry analysis of sequence variants in ADH and ALDH using alcohol-related phenotypes in a Native American community sample.

    Science.gov (United States)

    Peng, Qian; Gizer, Ian R; Libiger, Ondrej; Bizon, Chris; Wilhelmsen, Kirk C; Schork, Nicholas J; Ehlers, Cindy L

    2014-12-01

    Higher rates of alcohol use and other drug-dependence have been observed in some Native American (NA) populations relative to other ethnic groups in the US. Previous studies have shown that alcohol dehydrogenase (ADH) genes and aldehyde dehydrogenase (ALDH) genes may affect the risk of development of alcohol dependence, and that polymorphisms within these genes may differentially affect risk for the disorder depending on the ethnic group evaluated. We evaluated variations in the ADH and ALDH genes in a large study investigating risk factors for substance use in a NA population. We assessed ancestry admixture and tested for associations between alcohol-related phenotypes in the genomic regions around the ADH1-7 and ALDH2 and ALDH1A1 genes. Seventy-two ADH variants showed significant evidence of association with a severity level of alcohol drinking-related dependence symptoms phenotype. These significant variants spanned across the entire 7 ADH gene cluster regions. Two significant associations, one in ADH and one in ALDH2, were observed with alcohol dependence diagnosis. Seventeen variants showed significant association with the largest number of alcohol drinks ingested during any 24-hour period. Variants in or near ADH7 were significantly negatively associated with alcohol-related phenotypes, suggesting a potential protective effect of this gene. In addition, our results suggested that a higher degree of NA ancestry is associated with higher frequencies of potential risk variants and lower frequencies of potential protective variants for alcohol dependence phenotypes.

  10. Isolated tumoral pyruvate dehydrogenase can synthesize acetoin which inhibits pyruvate oxidation as well as other aldehydes.

    Science.gov (United States)

    Baggetto, L G; Lehninger, A L

    1987-05-29

    Oxidation of 1 mM pyruvate by Ehrlich and AS30-D tumor mitochondria is inhibited by acetoin, an unusual and important metabolite of pyruvate utilization by cancer cells, by acetaldehyde, methylglyoxal and excess pyruvate. The respiratory inhibition is reversed by other substrates added to pyruvate and also by 0.5 mM ATP. Kinetic properties of pyruvate dehydrogenase complex isolated from these tumor mitochondria have been studied. This complex appears to be able to synthesize acetoin from acetaldehyde plus pyruvate and is competitively inhibited by acetoin. The role of a new regulatory pattern for tumoral pyruvate dehydrogenase is presented.

  11. Isolated tumoral pyruvate dehydrogenase can synthesize acetoin which inhibits pyruvate oxidation as well as other aldehydes.

    Science.gov (United States)

    Baggetto, L G; Lehninger, A L

    1987-05-29

    Oxidation of 1 mM pyruvate by Ehrlich and AS30-D tumor mitochondria is inhibited by acetoin, an unusual and important metabolite of pyruvate utilization by cancer cells, by acetaldehyde, methylglyoxal and excess pyruvate. The respiratory inhibition is reversed by other substrates added to pyruvate and also by 0.5 mM ATP. Kinetic properties of pyruvate dehydrogenase complex isolated from these tumor mitochondria have been studied. This complex appears to be able to synthesize acetoin from acetaldehyde plus pyruvate and is competitively inhibited by acetoin. The role of a new regulatory pattern for tumoral pyruvate dehydrogenase is presented. PMID:3593337

  12. ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Takafumi Kuroda

    Full Text Available Cancer stem-like cells (CSCs/cancer-initiating cells (CICs are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas by the ALDEFLUOR assay. ALDH1(high cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high cells. ALDH1(high cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

  13. Allelic variants of ADH, ALDH and the five factor model of personality in alcohol dependence syndrome

    Directory of Open Access Journals (Sweden)

    S K Salujha

    2014-01-01

    Full Text Available Background: The etiology of alcohol dependence is a complex interplay of biopsychosocial factors. The genes for alcohol-metabolizing enzymes: Alcohol dehydrogenase (ADH2 and ADH3 and aldehyde dehydrogenase (ALDH2 exhibit functional polymorphisms. Vulnerability of alcohol dependence may also be in part due to heritable personality traits. Aim: To determine whether any association exists between polymorphisms of ADH2, ADH3 and ALDH2 and alcohol dependence syndrome in a group of Asian Indians. In addition, the personality of these patients was assessed to identify traits predisposing to alcoholism. Materials and Methods: In this study, 100 consecutive males with alcohol dependence syndrome attending the psychiatric outpatient department of a tertiary care service hospital and an equal number of matched healthy controls were included with their consent. Blood samples of all the study cases and controls were collected and genotyped for the ADH2, ADH3 and ALDH2 loci. Personality was evaluated using the neuroticism, extraversion, openness (NEO personality inventory and sensation seeking scale. Results: Allele frequencies of ADH2FNx012 (0.50, ADH3FNx011 (0.67 and ALSH2FNx012 (0.09 were significantly low in the alcohol dependent subjects. Personality traits of NEO personality inventory and sensation seeking were significantly higher when compared to controls. Conclusions: The functional polymorphisms of genes coding for alcohol metabolizing enzymes and personality traits of NEO and sensation seeking may affect the propensity to develop dependence.

  14. The ORF slr0091 of Synechocystis sp. PCC6803 encodes a high-light induced aldehyde dehydrogenase converting apocarotenals and alkanals

    KAUST Repository

    Trautmann, Danika

    2013-07-05

    Oxidative cleavage of carotenoids and peroxidation of lipids lead to apocarotenals and aliphatic aldehydes called alkanals, which react with vitally important compounds, promoting cytotoxicity. Although many enzymes have been reported to deactivate alkanals by converting them into fatty acids, little is known about the mechanisms used to detoxify apocarotenals or the enzymes acting on them. Cyanobacteria and other photosynthetic organisms must cope with both classes of aldehydes. Here we report that the Synechocystis enzyme SynAlh1, encoded by the ORF slr0091, is an aldehyde dehydrogenase that mediates oxidation of both apocarotenals and alkanals into the corresponding acids. Using a crude lysate of SynAlh1-expressing Escherichia coli cells, we show that SynAlh1 converts a wide range of apocarotenals and alkanals, with a preference for apocarotenals with defined chain lengths. As suggested by in vitro incubations and using engineered retinal-forming E. coli cells, we found that retinal is not a substrate for SynAlh1, making involvement in Synechocystis retinoid metabolism unlikely. The transcript level of SynAlh1 is induced by high light and cold treatment, indicating a role in the stress response, and the corresponding gene is a constituent of a stress-related operon. The assumptions regarding the function of SynAlh are further supported by the surprisingly high homology to human and plant aldehyde dehydrogenase that have been assigned to aldehyde detoxification. SynAlh1 is the first aldehyde dehydrogenase that has been shown to form both apocarotenoic and fatty acids. This dual function suggests that its eukaryotic homologs may also be involved in apocarotenal metabolism, a function that has not been considered so far. Aldehyde dehydrogenases play an important role in detoxification of reactive aldehydes. Here, we report on a cyanbacterial enzyme capable in converting two classes of lipid-derived aldehydes, apocaotenals and alkanals. The corresponding gene is a

  15. Relationship between genetic polymorphisms of alcohol and aldehyde dehydrogenases and esophageal squamous cell carcinoma risk in males

    Institute of Scientific and Technical Information of China (English)

    Chia-Fang Wu; Deng-Chyang Wu; Hon-Ki Hsu; Ein-Long Kao; Jang-Ming Lee; Cheng-Chieh Lin; Ming-Tsang Wu

    2005-01-01

    AIM: To investigate the association between the genetic polymorphisms of ADH2 and ALDH2, lifetime alcohol consumption and esophageal cancer risk in the Taiwanese men.METHODS: Between August 2000 and June 2003, 134 pathologically-proven esophageal squamous cell carcinoma male patients and 237 male controls were recruited from Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital in southern Taiwan.ADH2 and ALDH2 polymorphisms were genotyped using PCR-RFLP.RESULTS: Compared to those with ADH2*2/*2,individuals with ADH2*1/*2 and ADH2*1/*1 had 2.28-and 7.14-fold, respectively, increased risk of developing esophageal cancer (95%CI = 1.11-4.68 and 2.76-18.46)after adjusting for alcohol consumption and other covariates. The significant increased risk was also noted among subjects with ALDH2*1/*2 (adjusted OR (AOR)= 5.25, 95%CI = 2.47-11.19), when compared to those with ALDH2*1/*1. The increased risk of esophageal cancer was made greater, when subjects carried both ADH2*1/*1 and ALDH2*1/*2, compared to those with ADH2*1/*2 or ADH2*2/*2 and ALDH2*1/*1 (AOR = 36.79,95%CI = 9.36-144.65). Furthermore, we found a multiplicative effect of lifetime alcoholic consumption and genotypes (ADH2 and ALDH2) on esophageal cancer risk.CONCLUSION: Our findings suggest that polymorphisms of ADH2 and ALDH2 can modify the influence of alcoholic consumption on esophageal cancer risk.

  16. Isolation of an Aldehyde Dehydrogenase Involved in the Oxidation of Fluoroacetaldehyde to Fluoroacetate in Streptomyces cattleya

    Science.gov (United States)

    Murphy, Cormac D.; Moss, Steven J.; O'Hagan, David

    2001-01-01

    Streptomyces cattleya is unusual in that it produces fluoroacetate and 4-fluorothreonine as secondary metabolites. We now report the isolation of an NAD+-dependent fluoroacetaldehyde dehydrogenase from S. cattleya that mediates the oxidation of fluoroacetaldehyde to fluoroacetate. This is the first enzyme to be identified that is directly involved in fluorometabolite biosynthesis. Production of the enzyme begins in late exponential growth and continues into the stationary phase. Measurement of kinetic parameters shows that the enzyme has a high affinity for fluoroacetaldehyde and glycoaldehyde, but not acetaldehyde. PMID:11571203

  17. Simultaneous involvement of a tungsten-containing aldehyde:ferredoxin oxidoreductase and a phenylacetaldehyde dehydrogenase in anaerobic phenylalanine metabolism.

    Science.gov (United States)

    Debnar-Daumler, Carlotta; Seubert, Andreas; Schmitt, Georg; Heider, Johann

    2014-01-01

    Anaerobic phenylalanine metabolism in the denitrifying betaproteobacterium Aromatoleum aromaticum is initiated by conversion of phenylalanine to phenylacetate, which is further metabolized via benzoyl-coenzyme A (CoA). The formation of phenylacetate is catalyzed by phenylalanine transaminase, phenylpyruvate decarboxylase, and a phenylacetaldehyde-oxidizing enzyme. The presence of these enzymes was detected in extracts of cells grown with phenylalanine and nitrate. We found that two distinct enzymes are involved in the oxidation of phenylacetaldehyde to phenylacetate, an aldehyde:ferredoxin oxidoreductase (AOR) and a phenylacetaldehyde dehydrogenase (PDH). Based on sequence comparison, growth studies with various tungstate concentrations, and metal analysis of the enriched enzyme, AOR was shown to be a tungsten-containing enzyme, necessitating specific cofactor biosynthetic pathways for molybdenum- and tungsten-dependent enzymes simultaneously. We predict from the genome sequence that most enzymes of molybdopterin biosynthesis are shared, while the molybdate/tungstate uptake systems are duplicated and specialized paralogs of the sulfur-inserting MoaD and the metal-inserting MoeA proteins seem to be involved in dedicating biosynthesis toward molybdenum or tungsten cofactors. We also characterized PDH biochemically and identified both NAD(+) and NADP(+) as electron acceptors. We identified the gene coding for the enzyme and purified a recombinant Strep-tagged PDH variant. The homotetrameric enzyme is highly specific for phenylacetaldehyde, has cooperative kinetics toward the substrate, and shows considerable substrate inhibition. Our data suggest that A. aromaticum utilizes PDH as the primary enzyme during anaerobic phenylalanine degradation, whereas AOR is not essential for the metabolic pathway. We hypothesize a function as a detoxifying enzyme if high aldehyde concentrations accumulate in the cytoplasm, which would lead to substrate inhibition of PDH.

  18. Notch Signaling Is Associated With ALDH Activity And An Aggressive Metastatic Phenotype In Murine Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Xiaodong eMu

    2013-06-01

    Full Text Available Osteosarcoma (OS is the most common primary malignancy of bone, and pulmonary metastatic disease accounts for nearly all mortality. However, little is known about the biochemical signaling alterations that drive the progression of metastatic disease. Two murine OS cell populations, K7M2 and K12, are clonally related but differ significantly in their metastatic phenotypes and therefore represent excellent tools for studying metastatic OS molecular biology. K7M2 cells are highly metastatic, whereas K12 cells display limited metastatic potential. Here we report that the expression of Notch genes (Notch1, 2, 4 are up-regulated, including downstream targets Hes1 and Stat3, in the highly metastatic K7M2 cells compared to the less metastatic K12 cells, indicating that the Notch signaling pathway is more active in K7M2 cells. We have previously described that K7M2 cells exhibit higher levels of aldehyde dehydrogenase (ALDH activity. Here we report that K7M2 cell ALDH activity is reduced with Notch inhibition, suggesting that ALDH activity may be regulated in part by the Notch pathway. Notch signaling is also associated with increased resistance to oxidative stress, migration, invasion, and VEGF expression in vitro. However, Notch inhibition did not significantly alter K7M2 cell proliferation. In conclusion, we provide evidence that Notch signaling is associated with ALDH activity and increased metastatic behavior in OS cells. Both Notch and ALDH are putative molecular targets for the treatment and prevention of OS metastasis.

  19. cDNA cloning and analysis of betaine aldehyde dehydrogenase, a salt inducible enzyme in sugar beet

    Energy Technology Data Exchange (ETDEWEB)

    McCue, K.F.; Hanson, A.D. (Michigan State Univ., East Lansing (USA))

    1990-05-01

    Betaine accumulates and serves as a compatible osmolyte in some plants subjected to drought or salinity stress. The last enzyme in the betaine biosynthetic pathway is betaine aldehyde dehydrogenase (BADH). The activity of BADH increases in response to increasing salinity levels. This increase in activity corresponds to an increase in protein detectable by immunoblotting, and to an increase in the translatable BADH mRNA. BADH was cloned from a cDNA library constructed in {lambda}gt10 using poly(A){sup +} RNA from sugar beets salinized to 500 mM NaCl. cDNAs were size selected (>1kb) before ligation into the vector, and the library was screened with a spinach BADH cDNA probe. Three nearly full length clones obtained were confirmed as BADH by their nucleotide and deduced amino acid homology to spinach BADH. Clones averaged 1.8 kb and contained open reading frames of 500 amino acids at 80% identity with spinach BADH. RNA gel blot analysis of poly(A){sup +} RNA indicated that salinization to 500 mM NaCl resulted in a 5-fold increase of BADH mRNA level.

  20. 乙醛脱氢酶-1作为心肌干细胞有效标志物的实验研究%Aldehyde dehydrogenase-1 as an effective marker for cardiac stem cells

    Institute of Scientific and Technical Information of China (English)

    韦海珠; 胡琳洁; 梁冬

    2013-01-01

    目的 研究乙醛脱氢酶-1(ALDH-1)是否可以作为分选心肌干细胞(CSC)的有效标志物.方法 从裸鼠心脏分离培养细胞球,收集细胞球制成单细胞悬液,利用Aldefluor试剂结合流式细胞术来分选心脏球体细胞中的SSCloAldebr细胞(ALDH-1阳性细胞),通过增殖能力、克隆形成、表型分析及定向分化能力鉴定其干细胞(SC)的特性.结果 裸鼠心脏细胞无血清培养可形成细胞球,球体细胞中可检测到ALDH-1阳性细胞的存在;ALDH-1阳性细胞具有高增殖性、高克隆形成率及定向分化的能力,具有SC的特性.结论 裸鼠心脏中存在CSC;ALDH-1可以作为CSC有效的标志物.%Objective To investigate whether acetaldehyde dehydrogenase-1 ( ALDH-1 ) may be used as an effective marker for sorting of cardiac stem cells (CSC). Methods Cells were separated from the heart of nude mice and cultured, and then collected to prepare single cell suspension. Utilizing Aldefluor reagent in conjunction with flow cytometry, SSCloAldebr cells (ALDH-1 positive cells) were sorted from collected cardiac cells. Characteristics of the cardiac stem cells were identified by analyzing reproductive capacity, clone formation, phenotypes and oriented differentiation of the sorted cells. Results Through serum-free culture cardiac cells from the heart of nude mice formed heter-cell spheres. In spheroid cells ALDH-1 positive cells were found. ALDH-1 positive cells possessed characteristics of stem cells including high reproductive capacity, high clone forming rate and ability for oriented differentiation. Conclusion Cardiac stem cells exist in the heart of nude mice, and ALDH-1 may be used as an effective marker for cardiac stem cells.

  1. Association of ADH and ALDH Genes With Alcohol Dependence in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD) Sample

    Science.gov (United States)

    Kuo, Po-Hsiu; Kalsi, Gursharan; Prescott, Carol A.; Hodgkinson, Colin A.; Goldman, David; van den Oord, Edwin J.; Alexander, Jeffry; Jiang, Cizhong; Sullivan, Patrick F.; Patterson, Diana G.; Walsh, Dermot; Kendler, Kenneth S.; Riley, Brien P.

    2008-01-01

    Background: The genes coding for ethanol metabolism enzymes [alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] have been widely studied for their influence on the risk to develop alcohol dependence (AD). However, the relation between polymorphisms of these metabolism genes and AD in Caucasian subjects has not been clearly established. The present study examined evidence for the association of alcohol metabolism genes with AD in the Irish Affected Sib Pair Study of alcohol dependence. Methods: We conducted a case–control association study with 575 independent subjects who met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, AD diagnosis and 530 controls. A total of 77 single nucleotide polymorphisms (SNPs) in the seven ADH (ADH1-7) and two ALDH genes (ALDH1A1 and ALDH2) were genotyped using the Illumina GoldenGate protocols. Several statistical procedures were implemented to control for false discoveries. Results: All markers with minor allele frequency greater than 0.01 were in Hardy–Weinberg equilibrium. Numerous SNPs in ADH genes showed association with AD, including one marker in the coding region of ADH1C (rs1693482 in exon6, Ile271Gln). Haplotypic association was observed in the ADH5 and ADH1C genes, and in a long haplotype block formed by the ADH1A and ADH1B loci. We detected two significant interactions between pairs of markers in intron 6 of ADH6 and intron 12 of ALDH2 (p = 5 × 10−5), and 5′ of both ADH4 and ADH1A (p = 2 × 10−4). Conclusion: We found evidence for the association of several ADH genes with AD in a sample of Western European origin. The significant interaction effects between markers in ADH and ALDH genes suggest possible epistatic roles between alcohol metabolic enzymes in the risk for AD. PMID:18331377

  2. Improved tolerance to various abiotic stresses in transgenic sweet potato (Ipomoea batatas expressing spinach betaine aldehyde dehydrogenase.

    Directory of Open Access Journals (Sweden)

    Weijuan Fan

    Full Text Available Abiotic stresses are critical delimiters for the increased productivity and cultivation expansion of sweet potato (Ipomoea batatas, a root crop with worldwide importance. The increased production of glycine betaine (GB improves plant tolerance to various abiotic stresses without strong phenotypic changes, providing a feasible approach to improve stable yield production under unfavorable conditions. The gene encoding betaine aldehyde dehydrogenase (BADH is involved in the biosynthesis of GB in plants, and the accumulation of GB by the heterologous overexpression of BADH improves abiotic stress tolerance in plants. This study is to improve sweet potato, a GB accumulator, resistant to multiple abiotic stresses by promoted GB biosynthesis. A chloroplastic BADH gene from Spinacia oleracea (SoBADH was introduced into the sweet potato cultivar Sushu-2 via Agrobacterium-mediated transformation. The overexpression of SoBADH in the transgenic sweet potato improved tolerance to various abiotic stresses, including salt, oxidative stress, and low temperature. The increased BADH activity and GB accumulation in the transgenic plant lines under normal and multiple environmental stresses resulted in increased protection against cell damage through the maintenance of cell membrane integrity, stronger photosynthetic activity, reduced reactive oxygen species (ROS production, and induction or activation of ROS scavenging by the increased activity of free radical-scavenging enzymes. The increased proline accumulation and systemic upregulation of many ROS-scavenging genes in stress-treated transgenic plants also indicated that GB accumulation might stimulate the ROS-scavenging system and proline biosynthesis via an integrative mechanism. This study demonstrates that the enhancement of GB biosynthesis in sweet potato is an effective and feasible approach to improve its tolerance to multiple abiotic stresses without causing phenotypic defects. This strategy for trait

  3. In vivo ethanol elimination in man, monkey and rat: A lack of relationship between the ethanol metabolism and the hepatic activities of alcohol and aldehyde dehydrogenases

    Energy Technology Data Exchange (ETDEWEB)

    Zorzano, A. (Universidad de Barcelona (Spain)); Herrera, E. (Universidad de Madrid (Spain))

    1990-01-01

    The in vivo ethanol elimination in human subjects, monkeys and rats was investigated after an oral ethanol dosage. After 0.4 g. ethanol/kg of body weight, ethanol elimination was much slower in human subjects than in monkeys. In order to detect a rise in monkey plasma ethanol concentrations as early as observed in human subjects, ethanol had to be administered at a dose of 3 g/kg body weight. Ethanol metabolism in rats was also much faster than in human subjects. However, human liver showed higher alcohol dehydrogenase activity and higher low Km aldehyde dehydrogenase activity than rat liver. Thus, our data suggest a lack of relationship between hepatic ethanol-metabolizing activities and the in vivo ethanol elimination rate.

  4. Ethanol and acetaldehyde differentially alter extracellular dopamine and serotonin in Aldh2-knockout mouse dorsal striatum: A reverse microdialysis study.

    Science.gov (United States)

    Jamal, Mostofa; Ameno, Kiyoshi; Miki, Takanori; Tanaka, Naoko; Ito, Asuka; Ono, Junichiro; Takakura, Ayaka; Kumihashi, Mitsuru; Kinoshita, Hiroshi

    2016-01-01

    Dopamine (DA) and serotonin (5-HT) seem to be involved in several of the effects of ethanol (EtOH). Acetaldehyde (AcH), especially in the brain, induces effects that mimic those of EtOH. The purpose of this study was to investigate the effects of local perfusion of EtOH and AcH on extracellular DA and 5-HT in the dorsal striatum of Aldh2-knockout (Aldh2-KO) and wild-type (WT) mice. Aldh2-KO mice were used as a model of aldehyde dehydrogenase 2 deficiency in humans to examine the effects of AcH. Mice were perfused with Ringer's solution (control), EtOH (100, 200, or 500mM) and AcH (100, 200, or 500μM) into the dorsal striatum. Dialysate samples were collected every 5min, and then analyzed with HPLC coupled to an ECD. We found that local perfusion with 500mM EtOH increased extracellular levels of DA (p<0.05) in both Aldh2-KO and WT mice, while 5-HT levels remain unchanged. EtOH at a dose of 200mM also increased DA in WT mice, but this was limited to a 30-40-min time-point. In contrast, perfusion with 200 and 500μM AcH decreased both DA and 5-HT (p<0.05) in Aldh2-KO mice, but this decrease was not found in WT mice at any AcH dose, indicating an effect of AcH on DA and 5-HT levels. There were no genotype effects on the basal levels of DA and 5-HT. These results indicate that high EtOH can stimulate DA, whereas high AcH can depress both DA and 5-HT in the dorsal striatum of mice. PMID:26711020

  5. Diplotype Trend Regression Analysis of the ADH Gene Cluster and the ALDH2 Gene: Multiple Significant Associations with Alcohol Dependence

    Science.gov (United States)

    Luo, Xingguang; Kranzler, Henry R.; Zuo, Lingjun; Wang, Shuang; Schork, Nicholas J.; Gelernter, Joel

    2006-01-01

    The set of alcohol-metabolizing enzymes has considerable genetic and functional complexity. The relationships between some alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes and alcohol dependence (AD) have long been studied in many populations, but not comprehensively. In the present study, we genotyped 16 markers within the ADH gene cluster (including the ADH1A, ADH1B, ADH1C, ADH5, ADH6, and ADH7 genes), 4 markers within the ALDH2 gene, and 38 unlinked ancestry-informative markers in a case-control sample of 801 individuals. Associations between markers and disease were analyzed by a Hardy-Weinberg equilibrium (HWE) test, a conventional case-control comparison, a structured association analysis, and a novel diplotype trend regression (DTR) analysis. Finally, the disease alleles were fine mapped by a Hardy-Weinberg disequilibrium (HWD) measure (J). All markers were found to be in HWE in controls, but some markers showed HWD in cases. Genotypes of many markers were associated with AD. DTR analysis showed that ADH5 genotypes and diplotypes of ADH1A, ADH1B, ADH7, and ALDH2 were associated with AD in European Americans and/or African Americans. The risk-influencing alleles were fine mapped from among the markers studied and were found to coincide with some well-known functional variants. We demonstrated that DTR was more powerful than many other conventional association methods. We also found that several ADH genes and the ALDH2 gene were susceptibility loci for AD, and the associations were best explained by several independent risk genes. PMID:16685648

  6. Clinical significance of ALDH2 rs671 polymorphism in esophageal cancer: evidence from 31 case-control studies

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    Zhao TT

    2015-03-01

    Full Text Available Tingting Zhao,1* Chun Wang,1* Lili Shen,1* Dongying Gu,1 Zhi Xu,1 Xunlei Zhang,2 Yong Xu,1 Jinfei Chen1 1Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Oncology, Nantong Tumor Hospital, Nantong University, Nantong, People’s Republic of China *These authors contributed equally to this work Background: Aldehyde dehydrogenase 2 (ALDH2, a critical enzyme for the detoxification of alcohol, is associated with many types of cancers. To verify the relationship of ALDH2 rs671 G>A polymorphism and esophageal cancer (EC, we performed a meta-analysis of a total of 31 published data including 8,510 patients and 16,197 controls. Methods: The pooled odds ratio (OR and the 95% confidence interval (CI were calculated using a fixed or random-effects model. Heterogeneity (PH, publication bias, and sensitivity analysis were also determined. Results: Although a protective effort was found in the rs671 homozygote comparison (AA/GG: OR=0.69; 95% CI=0.48–0.98, the heterozygote comparison was apparently associated with the risk of EC, particularly in the Chinese population (AG/GG: OR=1.39; 95% CI=1.03–1.87. Alcohol consumption remarkably increased this risk, especially in the AG genotype. Drinking men with the AG genotype appeared to show a higher risk (AG/GG: OR=4.39; 95% CI=1.24–6.55 than drinking women. Conclusion: The present meta-analysis provided advanced information regarding the association of the ALDH2 A>G polymorphism and EC. Taken together, insights from this study suggested an enhanced effect on the development of EC through a genetic–environmental interaction. Keywords: aldehyde dehydrogenase-2, single nucleotide polymorphism, SNP, esophageal cancer, EC, meta-analysis

  7. Association of genetic polymorphisms in ADH and ALDH2 with risk of coronary artery disease and myocardial infarction: a meta-analysis.

    Science.gov (United States)

    Han, Hongguang; Wang, Huishan; Yin, Zongtao; Jiang, Hui; Fang, Minhua; Han, Jingsong

    2013-09-10

    Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for alcohol metabolism in humans. Emerging evidences have shown that functional polymorphisms in ADH and ALDH genes might play a critical role in increasing coronary artery disease (CAD) and myocardial infarction (MI) risks; however, individually published studies showed inconclusive results. The aim of this meta-analysis is to evaluate the associations between the genetic polymorphisms of ADH and ALDH genes with susceptibility to CAD and MI. A literature search was conducted on PubMed, Embase, Web of Science and Chinese BioMedical databases from inception through December 1st, 2012. Crude relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Twelve case-control studies were included with a total of 9616 subjects, including 2053 CAD patients, 1436 MI patients, and 6127 healthy controls. Meta-analysis showed that mutant genotypes (GA+AA) of the rs671 polymorphism in the ALDH2 gene were associated with increased risk of both CAD and MI (CAD: RR=1.20, 95%CI: 1.03-1.40, P=0.021; MI: RR=1.32, 95%CI: 1.11-1.57, P=0.002). However, there were no significant associations of ADH genetic polymorphisms to CAD and MI risks (CAD: RR=0.92, 95%CI: 0.73-1.15, P=0.445; MI: RR=0.93, 95%CI: 0.84-1.03, P=0.148). In conclusion, this meta-analysis provides strong evidence that ALDH2 rs671 polymorphism may be associated with increased risks of CAD and MI. However, further studies are still needed to accurately determine whether ADH genetic polymorphisms are associated with susceptibility to CAD and MI.

  8. Fatty Aldehyde and Fatty Alcohol Metabolism: Review and Importance for Epidermal Structure and Function

    Science.gov (United States)

    Rizzo, William B.

    2014-01-01

    Normal fatty aldehyde and alcohol metabolism is essential for epidermal differentiation and function. Long-chain aldehydes are produced by catabolism of several lipids including fatty alcohols, sphingolipids, ether glycerolipids, isoprenoid alcohols and certain aliphatic lipids that undergo α- or ω-oxidation. The fatty aldehyde generated by these pathways is chiefly metabolized to fatty acid by fatty aldehyde dehydrogenase (FALDH, alternately known as ALDH3A2), which also functions to oxidize fatty alcohols as a component of the fatty alcohol:NAD oxidoreductase (FAO) enzyme complex. Genetic deficiency of FALDH/FAO in patients with Sjögren-Larsson syndrome (SLS) results in accumulation of fatty aldehydes, fatty alcohols and related lipids (ether glycerolipids, wax esters) in cultured keratinocytes. These biochemical changes are associated with abnormalities in formation of lamellar bodies in the stratum granulosum and impaired delivery of their precursor membranes to the stratum corneum (SC). The defective extracellular SC membranes are responsible for a leaky epidermal water barrier and ichthyosis. Although lamellar bodies appear to be the pathogenic target for abnormal fatty aldehyde/alcohol metabolism in SLS, the precise biochemical mechanisms are yet to be elucidated. Nevertheless, studies in SLS highlight the critical importance of FALDH and normal fatty aldehyde/alcohol metabolism for epidermal function. PMID:24036493

  9. High ALDH activity identifies chemotherapy-resistant Ewing's sarcoma stem cells that retain sensitivity to EWS-FLI1 inhibition.

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    Ola Awad

    Full Text Available BACKGROUND: Cancer stem cells are a chemotherapy-resistant population capable of self-renewal and of regenerating the bulk tumor, thereby causing relapse and patient death. Ewing's sarcoma, the second most common form of bone tumor in adolescents and young adults, follows a clinical pattern consistent with the Cancer Stem Cell model - remission is easily achieved, even for patients with metastatic disease, but relapse remains frequent and is usually fatal. METHODOLOGY/PRINCIPAL FINDINGS: We have isolated a subpopulation of Ewing's sarcoma cells, from both human cell lines and human xenografts grown in immune deficient mice, which express high aldehyde dehydrogenase (ALDH(high activity and are enriched for clonogenicity, sphere-formation, and tumor initiation. The ALDH(high cells are resistant to chemotherapy in vitro, but this can be overcome by the ATP binding cassette transport protein inhibitor, verapamil. Importantly, these cells are not resistant to YK-4-279, a small molecule inhibitor of EWS-FLI1 that is selectively toxic to Ewing's sarcoma cells both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: Ewing's sarcoma contains an ALDH(high stem-like population of chemotherapy-resistant cells that retain sensitivity to EWS-FLI1 inhibition. Inhibiting the EWS-FLI1 oncoprotein may prove to be an effective means of improving patient outcomes by targeting Ewing's sarcoma stem cells that survive standard chemotherapy.

  10. Sjögren-Larsson syndrome: novel mutations in the ALDH3A2 gene in a French cohort.

    Science.gov (United States)

    Sarret, Catherine; Rigal, Mélanie; Vaurs-Barrière, Catherine; Dorboz, Imen; Eymard-Pierre, Eléonore; Combes, Patricia; Giraud, Geneviève; Wanders, Ronald J A; Afenjar, Alexandra; Francannet, Christine; Boespflug-Tanguy, Odile

    2012-01-15

    Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive disorder characterized by ichthyosis, spastic di- or tetraplegia and mental retardation due a defect of the fatty aldehyde dehydrogenase (FALDH), related to mutations in the ALDH3A2 gene. In this study, we screened a French cohort of patients with Sjögren-Larsson syndrome (SLS) for mutations in the ALDH3A2 gene. The five unrelated patients with typical SLS all present mutations in this gene. Three novel mutations were identified whereas three other ones were previously described. We also realized functional analyses at the mRNA level for two splice site mutations to study their deleterious consequences. Two of the previously described mutations had already been identified in the same region of Europe, suggesting a putative founder effect. We suggest that, (1) when clinical and MR features are present, direct sequencing of the ALDH3A2 gene in SLS is of particular interest without necessity of a skin biopsy for enzymatic assay in order to propose genetic counsel and (2) identification of mutations already described in the same population with putative founder effects may simplify genetic analysis in this context.

  11. Neurotransmitter alterations in embryonic succinate semialdehyde dehydrogenase (SSADH deficiency suggest a heightened excitatory state during development

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    Snead O Carter

    2008-11-01

    Full Text Available Abstract Background SSADH (aldehyde dehydrogenase 5a1 (Aldh5a1; γ-hydroxybutyric (GHB aciduria deficiency is a defect of GABA degradation in which the neuromodulators GABA and GHB accumulate. The human phenotype is that of nonprogressive encephalopathy with prominent bilateral discoloration of the globi pallidi and variable seizures, the latter displayed prominently in Aldh5a1-/- mice with lethal convulsions. Metabolic studies in murine neural tissue have revealed elevated GABA [and its derivatives succinate semialdehyde (SSA, homocarnosine (HC, 4,5-dihydroxyhexanoic acid (DHHA and guanidinobutyrate (GB] and GHB [and its analogue D-2-hydroxyglutarate (D-2-HG] at birth. Because of early onset seizures and the neurostructural anomalies observed in patients, we examined metabolite features during Aldh5a1-/- embryo development. Methods Embryos were obtained from pregnant dams sacrificed at E (embryo day of life 10–13, 14–15, 16–17, 18–19 and newborn mice. Intact embryos were extracted and metabolites quantified by isotope dilution mass spectrometry (n = 5–15 subjects, Aldh5a1+/+ and Aldh5a1-/- for each gestational age group. Data was evaluated using the t test and one-way ANOVA with Tukey post hoc analysis. Significance was set at the 95th centile. Results GABA and DHHA were significantly elevated at all gestational ages in Aldh5a1-/- mice, while GB was increased only late in gestation; SSA was not elevated at any time point. GHB and D-2-HG increased in an approximately linear fashion with gestational age. Correlative studies in human amniotic fluid from SSADH-deficient pregnancies (n = 5 also revealed significantly increased GABA. Conclusion Our findings indicate early GABAergic alterations in Aldh5a1-/- mice, possibly exacerbated by other metabolites, which likely induce a heightened excitatory state that may predispose neural networks to epilepsy in these animals.

  12. Polymorphisms in alcohol metabolism genes ADH1B and ALDH2, alcohol consumption and colorectal cancer.

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    Marta Crous-Bou

    Full Text Available BACKGROUND: Colorectal cancer (CRC is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included alcohol intake, which is mainly metabolized to acetaldehyde by alcohol dehydrogenase and further oxidized to acetate by aldehyde dehydrogenase; consequently, the role of genes in the alcohol metabolism pathways is of particular interest. The aim of this study is to analyze the association between SNPs in ADH1B and ALDH2 genes and CRC risk, and also the main effect of alcohol consumption on CRC risk in the study population. METHODOLOGY/PRINCIPAL FINDINGS: SNPs from ADH1B and ALDH2 genes, included in alcohol metabolism pathway, were genotyped in 1694 CRC cases and 1851 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. A positive association between alcohol consumption and CRC risk was observed in male participants from the Molecular Epidemiology of Colorectal Cancer study (MECC study (OR = 1.47; 95%CI = 1.18-1.81. Moreover, the SNPs rs1229984 in ADH1B gene was found to be associated with CRC risk: under the recessive model, the OR was 1.75 for A/A genotype (95%CI = 1.21-2.52; p-value = 0.0025. A path analysis based on structural equation modeling showed a direct effect of ADH1B gene polymorphisms on colorectal carcinogenesis and also an indirect effect mediated through alcohol consumption. CONCLUSIONS/SIGNIFICANCE: Genetic polymorphisms in the alcohol metabolism pathways have a potential role in colorectal carcinogenesis, probably due to the differences in the ethanol metabolism and acetaldehyde oxidation of these enzyme variants.

  13. Polymorphisms in Alcohol Metabolism Genes ADH1B and ALDH2, Alcohol Consumption and Colorectal Cancer

    Science.gov (United States)

    Crous-Bou, Marta; Rennert, Gad; Cuadras, Daniel; Salazar, Ramon; Cordero, David; Saltz Rennert, Hedy; Lejbkowicz, Flavio; Kopelovich, Levy; Monroe Lipkin, Steven; Bernard Gruber, Stephen; Moreno, Victor

    2013-01-01

    Background Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included alcohol intake, which is mainly metabolized to acetaldehyde by alcohol dehydrogenase and further oxidized to acetate by aldehyde dehydrogenase; consequently, the role of genes in the alcohol metabolism pathways is of particular interest. The aim of this study is to analyze the association between SNPs in ADH1B and ALDH2 genes and CRC risk, and also the main effect of alcohol consumption on CRC risk in the study population. Methodology/Principal Findings SNPs from ADH1B and ALDH2 genes, included in alcohol metabolism pathway, were genotyped in 1694 CRC cases and 1851 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. A positive association between alcohol consumption and CRC risk was observed in male participants from the Molecular Epidemiology of Colorectal Cancer study (MECC) study (OR = 1.47; 95%CI = 1.18-1.81). Moreover, the SNPs rs1229984 in ADH1B gene was found to be associated with CRC risk: under the recessive model, the OR was 1.75 for A/A genotype (95%CI = 1.21-2.52; p-value = 0.0025). A path analysis based on structural equation modeling showed a direct effect of ADH1B gene polymorphisms on colorectal carcinogenesis and also an indirect effect mediated through alcohol consumption. Conclusions/Significance Genetic polymorphisms in the alcohol metabolism pathways have a potential role in colorectal carcinogenesis, probably due to the differences in the ethanol metabolism and acetaldehyde oxidation of these enzyme variants. PMID:24282520

  14. Osmotic Regulation of Betaine Content in Leymus chinensis Under Saline-alkali Stress and Cloning and Expression of Betaine Aldehyde Dehydrogenase(BADH)Gene

    Institute of Scientific and Technical Information of China (English)

    CUI Xi-yan; WANG Yong; GUO Ji-xun

    2008-01-01

    The potted Leymus chinensis seedlings were treated with saline-alkali solution of six different(from Ⅰ to Ⅵ) concentrations.The results demonstrate that the betaine content and Betaine-aldehyde dehydrogenase(BADH:EC 1.2.1.8) activities have a direct relation with increased stressing time in the same treatment;both exhibit a single peak with increasing the concentration of saline-alkali solution,and number V shows the highest value.The BADH gene of Leymus chinensis Was cloned by RT-PCR and RACE technology and Was designated as LcBADH.The cDNA sequence of LcBADH Was 1774bp including the open reading frame(ORF)of 1521bp(coding 506 amino acids).The vector of prokaryotic expression was constructed by inserting the LcBADH gene fragment into pET30a(+)and transformed into E. coli BL21(DE3).The result of SDS-PAGE shows that the idio-protein with a molecular mass of 56.78 kDa was effectively expressed in the recombinant bacteria induced by isopropyl β-D-thiogalactoside(IPTG).

  15. Genetic polymorphisms in cytochrome P4502E1,alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males

    Institute of Scientific and Technical Information of China (English)

    Yan-Mei Guo; Qin Wang; Yan-Zhen Liu; Huei-Min Chen; Zhi Qi; Qing-Hong Guo

    2008-01-01

    AIM:To evaluate the association between genetic polymorphisms in CYP2E1,ALDH2 and ADHIB and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu province,in Chinese males.METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP2EI*cl/*c2,ALDH2*I/*2 and ADHIB "1/'1genotypes).A total of 80 esophageal cancer cases and 480 controls were recruited.RESULTS:Compared with controls,cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with > 30 drink-years (28.8% vs 13.5%).Heavier alcohol consumption and alcohol drinking with > 30 drink-years increased the risk of ESCC,with ORs (95% CI)of 3.20 (1.32-9.65) and 1.68 (0.96-3.21).CYP2E1(*cl/*cl),ALDH2 ('1/'2) and ADHIB (*1/*1) genotype frequencies were higher among patients with squamous cell carcinomas,at a level close to statistical significance (P = 0.014; P = 0.094; P = 0.0001 respectively).There were synergistic interactions among alcohol drinking and ALDH2,ADHIB and CYP2E1 genotypes.The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2*I/*2 as well as ADHIB encoded by ADHIB "1/'1 and CYP2E1 encoded by CYP2E1 *cl/*cl was higher than that in the never/rare-to-light drinkers with an active ALDH2 ('1/'1 genotype)as well as ADHIB ('1/'2 + *2/*2) and CYP2E1 (*c1/*c2+ *c2/*c2) genotypes,with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68),27.12(8.52-70.19) and 7.64 (2.82-11.31) respectively.The risk of the ESCC in moderate-to-heavy drinkers with ALDH2('1/'2) combined theADHIB ('1/'1) genotype orALDH2('11"2) combined the CYP2E1 (*cl/*cl) genotype leads to synergistic interactions,higher than drinkers with ALDH2 (* 1/* 1) + ADHIB ('1/'2 + *2/*2),ALDH2 (* 1/* 1)+ CYP2E1 (*cl/*c2 + *c2/*c2) respectively,ORs (95%CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively.Individuals with the ADHIB combined the CYP2E1genotype

  16. The effects of different concentrations of nitroglycerin on cardiac ischemia and reperfusion injury and the mechanism of mitochondrial acetaldehyde dehydrogenase 2%不同浓度硝酸甘油对心脏缺血/再灌注的作用及ALDH2的作用

    Institute of Scientific and Technical Information of China (English)

    王晓梅; 李正红; 夏满莉; 胡杰; 姜翠荣; 高琴

    2011-01-01

    目的 探讨不同浓度硝酸甘油(GTN)对离体大鼠心脏缺血/再灌注损伤的作用,进一步分析线粒体乙醛脱氢酶2(ALDH2)在其中的作用.方法 采用离体大鼠心脏Langendorff灌流方法,局部结扎冠状动脉左前降支30 min,复灌30 min复制缺血/再灌注模型.实验分五组,正常对照组,单纯缺血/再灌注组,GTN低浓度组(10 -8 mol/L GTN),中浓度组(10-7 mol/L GTN)及高浓度组(2×10 -6 mol/L GTN).测定心室动力学指标和复灌期间冠脉流出液中乳酸脱氢酶( lactate dehydrogenase,LDH)含量,RT-PCR测定左心室前壁心尖组织线粒体ALDH2基因mRNA表达水平.结果 与单纯缺血/再灌注组相比,GTN低浓度组左心室发展压(LVDP)、室内压最大上升/下降速率(±dp/dtmax)均增高,左心室舒张末压(LVEDP)降低,中浓度组无明显差异,高浓度组LVDP和±dp/dtmax均降低;LVEDP增高.与缺血/再灌注组相比,正常对照组和低浓度GTN组心肌组织ALDH2 mRNA表达增高,中浓度无明显差异,高浓度组大鼠心肌ALDH2 mRNA表达降低.结论 低浓度GTN可对抗心肌缺血/再灌注损伤,高浓度GTN加重损伤,中浓度GTN对损伤影响不大,此现象可能与不同浓度GTN引起心肌ALDH2的释放量不同有关.%Objective To investigate the effects of different concentrations of nitroglycerin ( GTN) in isolated rat hearts subjected to ischemia and reperfusion (I/R) injury and the role of mitochondrial acetaldehyde dehydrogenase 2 ( ALDH2). Methods The isolated perfused rat hearts were subjected to 30 min local ischemia and 30 min reperfusion. The rats were divided into control, I/R, low concentration GTN (10~8 mol/L GTN) , middle concentration GTN (10~7 mol/L GTN) group, high concentration GTN (2 xlO"6 mol/L GTN) groups. The ventricular hemodynamic parameters and lactate dehydrogenase (LDH) release during reperfusion were measured. The ALDH2 mRNA expression of left anterior myocardium was detected by reverse transcriptase polymerase chain

  17. The structure of retinal dehydrogenase type II at 2.7 A resolution: implications for retinal specificity.

    Science.gov (United States)

    Lamb, A L; Newcomer, M E

    1999-05-11

    Retinoic acid, a hormonally active form of vitamin A, is produced in vivo in a two step process: retinol is oxidized to retinal and retinal is oxidized to retinoic acid. Retinal dehydrogenase type II (RalDH2) catalyzes this last step in the production of retinoic acid in the early embryo, possibly producing this putative morphogen to initiate pattern formation. The enzyme is also found in the adult animal, where it is expressed in the testis, lung, and brain among other tissues. The crystal structure of retinal dehydrogenase type II cocrystallized with nicotinamide adenine dinucleotide (NAD) has been determined at 2.7 A resolution. The structure was solved by molecular replacement using the crystal structure of a mitochondrial aldehyde dehydrogenase (ALDH2) as a model. Unlike what has been described for the structures of two aldehyde dehydrogenases involved in the metabolism of acetaldehyde, the substrate access channel is not a preformed cavity into which acetaldehyde can readily diffuse. Retinal dehydrogenase appears to utilize a disordered loop in the substrate access channel to discriminate between retinaldehyde and short-chain aldehydes.

  18. Immobilisation and characterisation of biocatalytic co-factor recycling enzymes, glucose dehydrogenase and NADH oxidase, on aldehyde functional ReSyn™ polymer microspheres.

    Science.gov (United States)

    Twala, Busisiwe V; Sewell, B Trevor; Jordaan, Justin

    2012-05-10

    The use of enzymes in industrial applications is limited by their instability, cost and difficulty in their recovery and re-use. Immobilisation is a technique which has been shown to alleviate these limitations in biocatalysis. Here we describe the immobilisation of two biocatalytically relevant co-factor recycling enzymes, glucose dehydrogenase (GDH) and NADH oxidase (NOD) on aldehyde functional ReSyn™ polymer microspheres with varying functional group densities. The successful immobilisation of the enzymes on this new high capacity microsphere technology resulted in the maintenance of activity of ∼40% for GDH and a maximum of 15.4% for NOD. The microsphere variant with highest functional group density of ∼3500 μmol g⁻¹ displayed the highest specific activity for the immobilisation of both enzymes at 33.22 U mg⁻¹ and 6.75 U mg⁻¹ for GDH and NOD with respective loading capacities of 51% (0.51 mg mg⁻¹) and 129% (1.29 mg mg⁻¹). The immobilised GDH further displayed improved activity in the acidic pH range. Both enzymes displayed improved pH and thermal stability with the most pronounced thermal stability for GDH displayed on ReSyn™ A during temperature incubation at 65 °C with a 13.59 fold increase, and NOD with a 2.25-fold improvement at 45 °C on the same microsphere variant. An important finding is the suitability of the microspheres for stabilisation of the multimeric protein GDH.

  19. Effects of Betaine Aldehyde Dehydrogenase-Transgenic Soybean on Phosphatase Activities and Rhizospheric Bacterial Community of the Saline-Alkali Soil

    Directory of Open Access Journals (Sweden)

    Ying Nie

    2016-01-01

    Full Text Available The development of transgenic soybean has produced numerous economic benefits; however the potential impact of root exudates upon soil ecological systems and rhizospheric soil microbial diversity has also received intensive attention. In the present study, the influence of saline-alkali tolerant transgenic soybean of betaine aldehyde dehydrogenase on bacterial community structure and soil phosphatase during growth stages was investigated. The results showed that, compared with nontransgenic soybean as a control, the rhizospheric soil pH of transgenic soybean significantly decreased at the seedling stage. Compared to HN35, organic P content was 13.5% and 25.4% greater at the pod-filling stage and maturity, respectively. The acid phosphatase activity of SRTS was significantly better than HN35 by 12.74% at seedling, 14.03% at flowering, and 59.29% at podding, while alkaline phosphatase achieved maximum activity in the flowering stage and was markedly lower than HN35 by 13.25% at pod-filling. The 454 pyrosequencing technique was employed to investigate bacterial diversity, with a total of 25,499 operational taxonomic units (OTUs obtained from the 10 samples. Notably, the effect of SRTS on microbial richness and diversity of rhizospheric soil was marked at the stage of podding and pod-filling. Proteobacteria, Acidobacteria, and Actinobacteria were the dominant phyla among all samples. Compared with HN35, the relative abundance of Proteobacteria was lower by 2.01%, 2.06%, and 5.28% at the stage of seedling, at pod-bearing, and at maturity. In genus level, the relative abundance of Gp6, Sphingomonas sp., and GP4 was significantly inhibited by SRTS at the stage of pod-bearing and pod-filling.

  20. Effect of ALDH2 activation against myocardial ischemia/reperfusion injury in diabetic rat%激动乙醛脱氢酶2对抗糖尿病大鼠心肌缺血/再灌注损伤的作用

    Institute of Scientific and Technical Information of China (English)

    王洪巨; 康品方; 叶红伟; 王晓梅; 于影; 张晔; 汤阳; 高琴

    2012-01-01

    目的:探讨激动乙醛脱氢酶2(ALDH2)在糖尿病大鼠心肌损伤中的作用.方法:腹腔注射55mg/kg链脲佐菌素复制糖尿病大鼠模型,分为糖尿病组和乙醇+糖尿病组(n=8).8周后行离体心肌缺血/再灌注(L/R),测定心室动力学指标和复灌期间冠脉流出液中乳酸脱氢酶(LDH)含量.测定空腹血糖、糖化血红蛋白(HbA1c)水平.RT-PCR和Western blot测定左心室前壁心尖组织线粒体ALDH2 mRNA和蛋白表达.结果:与正常大鼠心肌I/R相比,糖尿病大鼠左室发展压、左心室最大上升和下降速率、左室做功进一步下降,左室舒张末压抬高,复灌期冠脉流出液中LDH释放增多,心室ALDH2 mRNA和蛋白表达降低;与糖尿病大鼠心肌I/R相比,ALDH2激动剂乙醇明显促进左室发展压、左心室最大上升和下降速率、左室做功的恢复,降低左室舒张末压,同时降低HbA1c水平和LDH的释放,ALDH2 mRNA和蛋白表达增高.结论:糖尿病大鼠心肌缺血/再灌注时,心肌ALDH2表达降低;增强ALDH2在糖尿病大鼠心肌中的表达可发挥保护作用.%Objective: To observe the role of activation of aldehyde dehydrogenase 2 (AIDH2) on rayocaidial ischemia/repeifusion (1/ R) injury in diabetic rats. Methods: Diabetic rat model was simulated by intraperitoneal injection 55 mg/kg slreptozotocin (STZ) and divided into diabetes and ethanol + diabetes groups( n = 8). After 8 weeks, myocardial ischemia/repeifusion model was mimicked in vitro. The ventricular dynamical parameters and lactate dehydrogenase (LDH) content in coronary flow were determined. The fasting blood glucose and glyco-sylated hemoglobin (HbAlc) level were determined by automatic biochemistry analyzer. The ALDH2 mRNA and protein expressions of left anterior myocardium were evaluated by RT-PCR and Western blot. Results: In contrast to I/R in normal rat, in diabetic rat, left ventricular development pressure (LVDP), maximal rise/fall rate of left ventricular pressure (

  1. NADH fluorescence lifetime analysis of the effect of magnesium ions on ALDH2

    Science.gov (United States)

    ALDH2 catalyzes oxidation of toxic aldehydes to their corresponding carboxylic acids. Magnesium ions influence enzyme activity in part by increasing NADH binding affinity. Traditional fluorescence measurements have monitored the blue shift of the NADH fluorescence spectrum to elucidate the extent of...

  2. The role of combined detection of Ki-67 and ALDH1 in predicting the effectiveness of neoadjuvant chemotherapy in patients with triple-negative breast cancer%Ki-67和ALDH1联合检测判断三阴性乳腺癌新辅助化疗效果的价值

    Institute of Scientific and Technical Information of China (English)

    姚宇锋; 龚建平; 唐金海; 秦建伟

    2013-01-01

    目的 探讨Ki-67和乙醛脱氢酶1(ALDH1)联合检测对判断三阴性乳腺癌(TNBC)新辅助化疗(NACT)效果的价值.方法 回顾性分析完成NACT的52例TNBC患者资料,分析化疗前Ki 67和ALDH1的不同表达情况与NACT后病理完全缓解(pCR)之间的相关性.结果 52例中,20例(38.5 %)NACT后获得pCR.Ki-67阳性表达组pCR率65.2%(15/23),高于Ki-67阴性表达组的17.2%(5/29)(P<0.05).ALDH1阳性表达组pCR率15.6%(5/32),低于ALDH1阴性表达组的75.0%(15/20)(P<0.01).Ki-67阳性且ALDH1阴性表达组pCR率为93.8%(15/16),高于Ki-67阳性且ALDH1阳性表达组或Ki-67阴性且ALDH1阳性表达组(P<0.05).结论 TNBC组织中Ki-67阳性且ALDH1阴性表达患者对NACT效果好,Ki-67阳性且ALDH1阴性可作为预测TNBC的NACT疗效的分子标记物.%Objective To evaluate the role of combined detection of Ki-67 and aldehyde dehydrogenase KALDH1) in predicting the effectiveness of neoadjuvant chemotherapy(NACT) in the patients with triple-negative breast cancer(TNBC). Methods Data of 52 TNBC patients treated with NACT were retrospectively reviewed. The relationship between the different expressions of Ki-67 and ALDH1 and the pathological complete remission(pCR) rate was analyzed. Results The pCR rate in 52 cases was 38. 5% (20/52). The pCR rate of the patients with positive expression of Ki-67 was 65.2.%(15/23), which was significantly higher than 17.2% (5/29) of those with Ki-67 negative-expression(P<0. 05). The pCR rate of the patients with positive expression of ALDHI was 15. 6% (5/32), which was significantly lower than 75. 0% ( 15/20) of those with negative expression of ALDHI (P<0. 01). The pCR rate in the patients with positive expression of Ki-67 and negative expression of ALDHI was 93. 8% (15/16), which was significantly higher than that of the patients with positive expression of Ki-67 and positive expression of ALDHI or the patients with negative expression of Ki-67 and positive expression of ALDHI

  3. The influence of the stem cell marker ALDH and the EGFR-PI3 kinase act signaling pathway on the radiation resistance of human tumor cell lines

    International Nuclear Information System (INIS)

    present study was to investigate the role of CSCs in resistance of radioselected subclones of non-small cell lung cancer (NSCLC) and breast cancer cells to irradiation. Additionally, the role of EGFR dependent PI3K/Akt/DNA-PKcs signaling in the context of CSC-mediated radiotherapy resistance was investigated. The following major results were obtained: (1) Radioresistant tumor cells from NSCLC-A549 cells as well as SK-BR-3 breast cancer cells could be isolated in vitro by a radioselection process. (2) In line with the proposed CSC biological behaviors radioselected cells presented extended population doubling time and decreased plating efficiency. (3) Among identified potential CSC markers such as CD133, Oct-4, Sox2 or aldehyde dehydrogenase (ALDH) expression, solely expression of the embryonic stem cell marker Oct-4 was increased in the radio-selected SK-BR-3 cells. However, increased ALDH activity but not enhanced ALDH protein expression was associated with radioresis-tance of A549 cells. (4) Respectively, ALDH activity was found to be involved in radio-resistance partially through PI3K pathway. (5) Using an siRNA approach, a differential effect of ALDH1 vs ALDH2 in terms of post-irradiation survival of tumor cells was demonstrated. In this context and in contrast to the role of ALDH2 a prosurvival effect of ALDH1 could be observed. (6) Radioresistance of IR-selected tumor cells was partially mediated through EGFR/PI3K/DNA-PKcs-dependent accelerated repair of DNA-DSBs. Thus, based on the described major findings in this study it is proposed that targeting of PI3K/Akt pathway and ALDH1 might be effective approaches towards overcoming CSC-mediated radiotherapy resistance.

  4. A missense mutation in ALDH1A3 causes isolated microphthalmia/anophthalmia in nine individuals from an inbred Muslim kindred.

    Science.gov (United States)

    Mory, Adi; Ruiz, Francesc X; Dagan, Efrat; Yakovtseva, Evgenia A; Kurolap, Alina; Parés, Xavier; Farrés, Jaume; Gershoni-Baruch, Ruth

    2014-03-01

    Nine affected individuals with isolated anophthalmia/microphthalmia from a large Muslim-inbred kindred were investigated. Assuming autosomal-recessive mode of inheritance, whole-genome linkage analysis, on DNA samples from four affected individuals, was undertaken. Homozygosity mapping techniques were employed and a 1.5-Mbp region, homozygous in all affected individuals, was delineated. The region contained nine genes, one of which, aldehyde dehydrogenase 1 (ALDH1A3), was a clear candidate. This gene seems to encode a key enzyme in the formation of a retinoic-acid gradient along the dorsoventral axis during an early eye development and the development of the olfactory system. Sanger sequence analysis revealed a missense mutation, causing a substitution of valine (Val) to methionine (Met) at position 71. Analyzing the p.Val71Met missense mutation using standard open access software (MutationTaster online, PolyPhen, SIFT/PROVEAN) predicts this variant to be damaging. Enzymatic activity, studied in vitro, showed no changes between the mutated and the wild-type ALDH1A3 protein.

  5. Interaction of DRD2TaqI, COMT, and ALDH2 genes associated with bipolar II disorder comorbid with anxiety disorders in Han Chinese in Taiwan.

    Science.gov (United States)

    Hu, Ming-Chuan; Lee, Sheng-Yu; Wang, Tzu-Yun; Chang, Yun-Hsuan; Chen, Shiou-Lan; Chen, Shih-Heng; Chu, Chun-Hsien; Wang, Chen-Lin; Lee, I Hui; Chen, Po See; Yang, Yen Kuang; Lu, Ru-Band

    2015-06-01

    It is hypothesized that dopaminergic genes-dopamine type-2 receptor (DRD2), aldehyde dehydrogenase 2 (ALDH2), and catechol-O-methyltransferase (COMT)-are associated with bipolar disorder (BP) and anxiety disorder (AD). Bipolar II (BP-II) is reported to be highly comorbid with AD. We examined whether interactions among these three genes are susceptibility factors in BP-II with AD (BP-II(+AD)) and without AD (BP-II(-AD)). In this study, we hypothesize that the interaction of the dopaminergic genes between BP-II(+AD) and BP-II(-AD) is significant different. We recruited 1260 participants: 495 with BP-II(-AD), 170 with BP-II(+AD), and 595 healthy controls without BP-II or AD. Genotyping was done using polymerase chain reactions plus restriction fragment length polymorphism analysis. Genotypic frequencies of the DRD2TaqIA, COMT, and ALDH2 polymorphisms between the two BP-II groups were nonsignificant. In logistic regression, the ALDH2 and DRD2TaqIA genes showed a main effect that was protective against BP-II(-AD) (odds ratio [OR] = 0.497, p = 0.010, and OR = 0.415, p = 0.017, respectively). The interaction of DRD2TaqIA A1/A1 and ALDH2*1/*1 had a significant risk effect on the BP-II(-AD) group (OR = 7.177, p II(-AD) (OR = 0.205, p = 0.047). All of the significant results described above are found only in BP-II(-AD). This study supports the hypothesis the interaction of the dopaminergic genes between BP-II(+AD) and BP-II(-AD) is significant different,, and provides additional evidence that the DRD2TaqIA A1/A1, ALDH2*1/*1 and COMT genes interact in BP-II(-AD) but not in BP-II(+AD). PMID:25430946

  6. The influence of the stem cell marker ALDH and the EGFR-PI3 kinase act signaling pathway on the radiation resistance of human tumor cell lines; Der Einfluss des Stammzellmarkers ALDH und des EGFR-PI3 Kinase-Akt Signalwegs auf die Strahlenresistenz humaner Tumorzelllinien

    Energy Technology Data Exchange (ETDEWEB)

    Mihatsch, Julia

    2014-07-14

    present study was to investigate the role of CSCs in resistance of radioselected subclones of non-small cell lung cancer (NSCLC) and breast cancer cells to irradiation. Additionally, the role of EGFR dependent PI3K/Akt/DNA-PKcs signaling in the context of CSC-mediated radiotherapy resistance was investigated. The following major results were obtained: (1) Radioresistant tumor cells from NSCLC-A549 cells as well as SK-BR-3 breast cancer cells could be isolated in vitro by a radioselection process. (2) In line with the proposed CSC biological behaviors radioselected cells presented extended population doubling time and decreased plating efficiency. (3) Among identified potential CSC markers such as CD133, Oct-4, Sox2 or aldehyde dehydrogenase (ALDH) expression, solely expression of the embryonic stem cell marker Oct-4 was increased in the radio-selected SK-BR-3 cells. However, increased ALDH activity but not enhanced ALDH protein expression was associated with radioresis-tance of A549 cells. (4) Respectively, ALDH activity was found to be involved in radio-resistance partially through PI3K pathway. (5) Using an siRNA approach, a differential effect of ALDH1 vs ALDH2 in terms of post-irradiation survival of tumor cells was demonstrated. In this context and in contrast to the role of ALDH2 a prosurvival effect of ALDH1 could be observed. (6) Radioresistance of IR-selected tumor cells was partially mediated through EGFR/PI3K/DNA-PKcs-dependent accelerated repair of DNA-DSBs. Thus, based on the described major findings in this study it is proposed that targeting of PI3K/Akt pathway and ALDH1 might be effective approaches towards overcoming CSC-mediated radiotherapy resistance.

  7. Purification, crystallization and preliminary X-ray analysis of recombinant betaine aldehyde dehydrogenase 2 (OsBADH2), a protein involved in jasmine aroma, from Thai fragrant rice (Oryza sativa L.)

    International Nuclear Information System (INIS)

    Crystals of betaine aldehyde dehydrogenase 2 from rice (O. sativa L.) belonged to a C-centred orthorhombic space group and diffraceted X-rays to 2.6 Å resolution. Fragrant rice (Oryza sativa L.) betaine aldehyde dehydrogenase 2 (OsBADH2) is a key enzyme in the synthesis of fragrance aroma compounds. The extremely low activity of OsBADH2 in catalyzing the oxidation of acetaldehyde is believed to be crucial for the accumulation of the volatile compound 2-acetyl-1-pyrroline (2AP) in many scented plants, including fragrant rice. Recombinant fragrant rice OsBADH2 was expressed in Escherichia coli as an N-terminal hexahistidine fusion protein, purified using Ni Sepharose affinity chromatography and crystallized using the microbatch method. Initial crystals were obtained within 24 h using 0.1 M Tris pH 8.5 with 30%(w/v) PEG 4000 and 0.2 M magnesium chloride as the precipitating agent at 291 K. Crystal quality was improved when the enzyme was cocrystallized with NAD+. Improved crystals were grown in 0.1 M HEPES pH 7.4, 24%(w/v) PEG 4000 and 0.2 M ammonium chloride and diffracted to beyond 2.95 Å resolution after being cooled in a stream of N2 immediately prior to X-ray diffraction experiments. The crystals belonged to space group C2221, with unit-cell parameters a = 66.03, b = 183.94, c = 172.28 Å. An initial molecular-replacement solution has been obtained and refinement is in progress

  8. Common variation at 1q24.1 (ALDH9A1 is a potential risk factor for renal cancer.

    Directory of Open Access Journals (Sweden)

    Marc Y R Henrion

    Full Text Available So far six susceptibility loci for renal cell carcinoma (RCC have been discovered by genome-wide association studies (GWAS. To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA. A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (Pcombined =2.30x10-8. Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1. We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; Pcombined =2.73x10-5. While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation.

  9. The thiocarbamate disulphide drug, disulfiram induces osteopenia in rats by inhibition of osteoblast function due to suppression of acetaldehyde dehydrogenase activity.

    Science.gov (United States)

    Mittal, Monika; Khan, Kainat; Pal, Subhashis; Porwal, Konica; China, Shyamsundar Pal; Barbhuyan, Tarun K; Baghel, Khemraj S; Rawat, Tara; Sanyal, Sabyasachi; Bhadauria, Smrati; Sharma, Vishnu L; Chattopadhyay, Naibedya

    2014-05-01

    Dithiocarbamates (DTC), a sulfhydryl group containing compounds, are extensively used by humans that include metam and thiram due to their pesticide properties, and disulfiram (DSF) as an alcohol deterrent. We screened these DTC in an osteoblast viability assay. DSF exhibited the highest cytotoxicity (IC50 488nM). Loss in osteoblast viability and proliferation was due to induction of apoptosis via G1 arrest. DSF treatment to osteoblasts reduced glutathione (GSH) levels and exogenous addition of GSH prevented DSF-induced reactive oxygen species generation and osteoblast apoptosis. DSF also inhibited osteoblast differentiation in vitro and in vivo, and the effect was associated with inhibition of aldehyde dehydrogenase (ALDH) activity. Out of various ALDH isozymes, osteoblasts expressed only ALDH2 and DSF downregulated its transcript as well as activity. Alda-1, a specific activator of ALDH2, stimulated osteoblast differentiation. Subcutaneous injection of DSF over the calvarium of new born rats reduced the differentiation phenotype of calvarial osteoblasts but increased the mRNA levels of Runx-2 and osteocalcin. DSF treatment at a human-equivalent dose of 30 mg/kg p.o. to adult Sprague Dawley rats caused trabecular osteopenia and suppressed the formation of mineralized nodule by bone marrow stromal cells. Moreover, DSF diminished bone regeneration at the fracture site. In growing rats, DSF diminished growth plate height, primary and secondary spongiosa, mineralized osteoid and trabecular strength. Substantial decreased bone formation was also observed in the cortical site of these rats. We conclude that DSF has a strong osteopenia inducing effect by impairing osteoblast survival and differentiation due to the inhibition of ALDH2 function. PMID:24496638

  10. ALDH1A2 (RALDH2 genetic variation in human congenital heart disease

    Directory of Open Access Journals (Sweden)

    Mesquita Sonia MF

    2009-11-01

    Full Text Available Abstract Background Signaling by the vitamin A-derived morphogen retinoic acid (RA is required at multiple steps of cardiac development. Since conversion of retinaldehyde to RA by retinaldehyde dehydrogenase type II (ALDH1A2, a.k.a RALDH2 is critical for cardiac development, we screened patients with congenital heart disease (CHDs for genetic variation at the ALDH1A2 locus. Methods One-hundred and thirty-three CHD patients were screened for genetic variation at the ALDH1A2 locus through bi-directional sequencing. In addition, six SNPs (rs2704188, rs1441815, rs3784259, rs1530293, rs1899430 at the same locus were studied using a TDT-based association approach in 101 CHD trios. Observed mutations were modeled through molecular mechanics (MM simulations using the AMBER 9 package, Sander and Pmemd programs. Sequence conservation of observed mutations was evaluated through phylogenetic tree construction from ungapped alignments containing ALDH8 s, ALDH1Ls, ALDH1 s and ALDH2 s. Trees were generated by the Neighbor Joining method. Variations potentially affecting splicing mechanisms were cloned and functional assays were designed to test splicing alterations using the pSPL3 splicing assay. Results We describe in Tetralogy of Fallot (TOF the mutations Ala151Ser and Ile157Thr that change non-polar to polar residues at exon 4. Exon 4 encodes part of the highly-conserved tetramerization domain, a structural motif required for ALDH oligomerization. Molecular mechanics simulation studies of the two mutations indicate that they hinder tetramerization. We determined that the SNP rs16939660, previously associated with spina bifida and observed in patients with TOF, does not affect splicing. Moreover, association studies performed with classical models and with the transmission disequilibrium test (TDT design using single marker genotype, or haplotype information do not show differences between cases and controls. Conclusion In summary, our screen indicates that

  11. [Effects of panthenol and carnitine on aldehyde metabolic enzymes in rats with tetrachloromethane-induced liver injury].

    Science.gov (United States)

    Satanovskaia, V I; Pron'ko, P S; Gaĭshmanova, A V; Miskevich, D A

    2009-01-01

    Tetrachloromethane (2 g/kg, intragastric) produced a decrease in the activity of NAD- and NADH- dependent aldehyde dehydrogenases with high Km for aldehydes in rat liver. Panthenol and L-carnitine administered separately normalized the activity of aldehyde dehydrogenases, while a combination of the drugs did not produce any significant effect. PMID:19441727

  12. Microbial alcohol dehydrogenases: identification, characterization and engineering

    NARCIS (Netherlands)

    Machielsen, M.P.

    2007-01-01

    Keywords: alcohol dehydrogenase, laboratory evolution, rational protein engineering, Pyrococcus furiosus, biocatalysis, characterization, computational design, thermostability.   Alcohol dehydrogeases (ADHs) catalyze the interconversion of alcohols, aldehydes and ketones. They display a wide variety

  13. Ethanol Metabolism by HeLa Cells Transduced with Human Alcohol Dehydrogenase Isoenzymes: Control of the Pathway by Acetaldehyde Concentration†

    Science.gov (United States)

    Matsumoto, Michinaga; Cyganek, Izabela; Sanghani, Paresh C.; Cho, Won Kyoo; Liangpunsakul, Suthat; Crabb, David W.

    2010-01-01

    Background Human class I alcohol dehydrogenase 2 isoenzymes (encoded by the ADH1B locus) have large differences in kinetic properties; however, individuals inheriting the alleles for the different isoenzymes exhibit only small differences in alcohol elimination rates. This suggests that other cellular factors must regulate the activity of the isoenzymes. Methods The activity of the isoenzymes expressed from ADH1B*1, ADH1B*2, and ADH1B*3 cDNAs was examined in stably transduced HeLa cell lines, including lines which expressed human low Km aldehyde dehydrogenase (ALDH2). The ability of the cells to metabolize ethanol was compared with that of HeLa cells expressing rat class I ADH (HeLa-rat ADH cells), rat hepatoma (H4IIEC3) cells, and rat hepatocytes. Results The isoenzymes had similar protein half-lives in the HeLa cells. Rat hepatocytes, H4IIEC3 cells, and HeLa-rat ADH cells oxidized ethanol much faster than the cells expressing the ADH1B isoenzymes. This was not explained by high cellular NADH levels or endogenous inhibitors; but rather because the activity of the β1 and β2 ADHs were constrained by the accumulation of acetaldehyde, as shown by the increased rate of ethanol oxidation by cell lines expressing β2 ADH plus ALDH2. Conclusion The activity of the human β2 ADH isoenzyme is sensitive to inhibition by acetaldehyde, which likely limits its activity in vivo. This study emphasizes the importance of maintaining a low steady–state acetaldehyde concentration in hepatocytes during ethanol metabolism. PMID:21166830

  14. STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH+/CD133+ stem cell-like human colon cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells. ► STAT3 inhibitor, FLLL32 inhibits P-STAT3 and STAT3 target genes in colon cancer stem-like cells. ► Inhibition of STAT3 resulted in decreased cell viability and reduced numbers of tumorspheres. ► STAT3 is required for survival and tumorsphere forming capacity in colon cancer stem-like cells. ► Targeting STAT3 in cancer stem-like cells may offer a novel treatment approach for colon cancer. -- Abstract: Persistent activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in colon cancer. Increasing evidence suggests the existence of a small population of colon cancer stem or cancer-initiating cells may be responsible for tumor initiation, metastasis, and resistance to chemotherapy and radiation. Whether STAT3 plays a role in colon cancer-initiating cells and the effect of STAT3 inhibition is still unknown. Flow cytometry was used to isolate colon cancer stem-like cells from three independent human colon cancer cell lines characterized by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulation (ALDH+/CD133+). The effects of STAT3 inhibition in colon cancer stem-like cells were examined. The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells and was reduced by a STAT3-selective small molecular inhibitor, FLLL32. FLLL32 also inhibited the expression of potential STAT3 downstream target genes in colon cancer stem-like cells including survivin, Bcl-XL, as well as Notch-1, -3, and -4, which may be involved in stem cell function. Furthermore, FLLL32 inhibited cell viability and tumorsphere formation as well as induced cleaved caspase-3 in colon cancer stem-like cells. FLLL32 is more potent than curcumin as evidenced with lower IC50 in colon cancer stem-like cells. In summary, our results indicate that STAT3 is a novel therapeutic target in colon cancer stem

  15. STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH{sup +}/CD133{sup +} stem cell-like human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Li, E-mail: lin.796@osu.edu [Center for Childhood Cancer, The Research Institute at Nationwide Children' s Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States); Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Fuchs, James; Li, Chenglong [Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210 (United States); Olson, Veronica [Center for Childhood Cancer, The Research Institute at Nationwide Children' s Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States); Bekaii-Saab, Tanios [Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210 (United States); Lin, Jiayuh, E-mail: lin.674@osu.edu [Center for Childhood Cancer, The Research Institute at Nationwide Children' s Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells. Black-Right-Pointing-Pointer STAT3 inhibitor, FLLL32 inhibits P-STAT3 and STAT3 target genes in colon cancer stem-like cells. Black-Right-Pointing-Pointer Inhibition of STAT3 resulted in decreased cell viability and reduced numbers of tumorspheres. Black-Right-Pointing-Pointer STAT3 is required for survival and tumorsphere forming capacity in colon cancer stem-like cells. Black-Right-Pointing-Pointer Targeting STAT3 in cancer stem-like cells may offer a novel treatment approach for colon cancer. -- Abstract: Persistent activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in colon cancer. Increasing evidence suggests the existence of a small population of colon cancer stem or cancer-initiating cells may be responsible for tumor initiation, metastasis, and resistance to chemotherapy and radiation. Whether STAT3 plays a role in colon cancer-initiating cells and the effect of STAT3 inhibition is still unknown. Flow cytometry was used to isolate colon cancer stem-like cells from three independent human colon cancer cell lines characterized by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulation (ALDH{sup +}/CD133{sup +}). The effects of STAT3 inhibition in colon cancer stem-like cells were examined. The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells and was reduced by a STAT3-selective small molecular inhibitor, FLLL32. FLLL32 also inhibited the expression of potential STAT3 downstream target genes in colon cancer stem-like cells including survivin, Bcl-XL, as well as Notch-1, -3, and -4, which may be involved in stem cell function. Furthermore, FLLL32 inhibited cell viability and tumorsphere formation as well as induced cleaved caspase-3 in colon cancer stem-like cells. FLLL32 is more potent than curcumin as evidenced with lower

  16. Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo.

    Directory of Open Access Journals (Sweden)

    Shriram Nallamshetty

    Full Text Available The effects of retinoids, the structural derivatives of vitamin A (retinol, on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA and its precursor all trans retinaldehyde (Rald, exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1, the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT demonstrated that Aldh1a1-deficient (Aldh1a1(-/- female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/- mice. In serum assays, Aldh1a1(-/- mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/- mesenchymal stem cells (MSCs expressed significantly higher levels of bone morphogenetic protein 2 (BMP2 and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/- mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/- mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.

  17. Isolation and Induced Expression of Betaine Aldehyde Dehydrogenase Gene from Spinach%菠菜甜菜碱醛脱氢酶基因的分离和诱导表达

    Institute of Scientific and Technical Information of China (English)

    张宁; 王蒂; 司怀军

    2004-01-01

    植物体内的甜菜碱由胆碱经两步不可逆的氧化反应合成,甜菜碱醛脱氢酶(betaine aldehyde dehydrogenase,BADH)是合成甜菜碱的关键酶,催化甜菜碱醛氧化为甜菜碱。本研究从菠菜叶片中分离了BADH基因,并将该基因与其它植物的BADH序列作了同源性分析,同时,证实了菠菜BADH基因的转录与表达受干旱和盐胁迫的诱导。

  18. Biochemical Analysis of Recombinant AlkJ from Pseudomonas putida Reveals a Membrane-Associated, Flavin Adenine Dinucleotide-Dependent Dehydrogenase Suitable for the Biosynthetic Production of Aliphatic Aldehydes

    OpenAIRE

    Kirmair, Ludwig; Skerra, Arne

    2014-01-01

    The noncanonical alcohol dehydrogenase AlkJ is encoded on the alkane-metabolizing alk operon of the mesophilic bacterium Pseudomonas putida GPo1. To gain insight into the enzymology of AlkJ, we have produced the recombinant protein in Escherichia coli and purified it to homogeneity using His6 tag affinity and size exclusion chromatography (SEC). Despite synthesis in the cytoplasm, AlkJ was associated with the bacterial cell membrane, and solubilization with n-dodecyl-β-d-maltoside was necessa...

  19. Efficient expression of codon-adapted human acetaldehyde dehydrogenase 2 cDNA with 6×His tag in Pichia pastoris

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Human mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) catalyzes the oxidation of acetaldehyde to acetic acid. Therefore, ALDH2 has therapeutic potential in detoxification of acetaldehyde. Further-more, ALDH2 catalyzes nitroglycerin to nitrate and 1, 2-glyceryldinitrate during therapy for angina pectoris, myocardial infarction, and heart failure. Large quantities of ALDH2 will be needed for potential clinical practice. In this study, Pichia pastoris was used as a platform for expression of human ALDH2. Based on the ALDH2*1 cDNA sequence, we designed ALDH2 cDNA by choosing the P. pastoris preferred codons and by decreasing the G + C content level. The sequence was synthesized using the overlap extension PCR method. The cDNA and 6×His tags were subcloned into the plasmid pPIC9K. The recombinant protein was expressed in P. pastoris GS115 and purified using Ni2+-Sepharose affinity chromatography. The amount of secreted protein in the culture was 80 mg/L in shake-flask cultivation and 260 mg/L in high-density bioreactor fermentation. Secreted ALDH2 was easily purified from the culture supernatant by using Ni2+-Sepharose affinity chromatography. After purification of the fermentation supernatant, the enzyme had a specific activity of 1.2 U/mg protein. The yield was about 16 mg/L in a shake flask culture of P. pastoris GS115 which contained the original human ALDH2*1 cDNA.

  20. Efficient expression of codon-adapted human acetaldehyde dehydrogenase 2 cDNA with 6×His tag in Pichia pastoris

    Institute of Scientific and Technical Information of China (English)

    ZHAO YuFeng; LEI MingKe; WU YuanXin; ZHANG ZiSheng; WANG CunWen

    2009-01-01

    Human mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) catalyzes the oxidation of acetaldehyde to acetic acid. Therefore, ALDH2 has therapeutic potential in detoxification of acetaldehyde. Furthermore, ALDH2 catalyzes nitroglycerin to nitrate and 1, 2-glyceryldinitrate during therapy for angina pectoris, myocardial infarction, and heart failure. Large quantities of ALDH2 will be needed for potential clinical practice. In this study, Pichia pastoris was used as a platform for expression of human ALDH2.Based on the ALDH2~*1 cDNA sequence, we designed ALDH2 cDNA by choosing the P. pastoris preferred codons and by decreasing the G + C content level. The sequence was synthesized using the overlap extension PCR method. The cDNA and 6×His tags were subcloned into the plasmid pPIC9K.The recombinant protein was expressed in P. pastoris GS115 and purified using Ni~(2+)-Sepharose affinity chromatography. The amount of secreted protein in the culture was 80 mg/L in shake-flask cultivation and 260 mglL in high-density bioreactor fermentation. Secreted ALDH2 was easily purified from the culture supernatant by using Ni2+-Sepharose affinity chromatography. After purification of the fermentation supernatant, the enzyme had a specific activity of 1.2 U/mg protein. The yield was about 16 mg/L in a shake flask culture of P. pastoris GS115 which contained the original human ALDH2~*1 cDNA.

  1. Fatty aldehydes in cyanobacteria are a metabolically flexible precursor for a diversity of biofuel products.

    Directory of Open Access Journals (Sweden)

    Brett K Kaiser

    Full Text Available We describe how pathway engineering can be used to convert a single intermediate derived from lipid biosynthesis, fatty aldehydes, into a variety of biofuel precursors including alkanes, free fatty acids and wax esters. In cyanobacteria, long-chain acyl-ACPs can be reduced to fatty aldehydes, and then decarbonylated to alkanes. We discovered a cyanobacteria class-3 aldehyde-dehydrogenase, AldE, that was necessary and sufficient to instead oxidize fatty aldehyde precursors into fatty acids. Overexpression of enzymes in this pathway resulted in production of 50 to 100 fold more fatty acids than alkanes, and the fatty acids were secreted from the cell. Co-expression of acyl-ACP reductase, an alcohol-dehydrogenase and a wax-ester-synthase resulted in a third fate for fatty aldehydes: conversion to wax esters, which accumulated as intracellular lipid bodies. Conversion of acyl-ACP to fatty acids using endogenous cyanobacterial enzymes may allow biofuel production without transgenesis.

  2. Microbial alcohol dehydrogenases: identification, characterization and engineering

    OpenAIRE

    Machielsen, M.P.

    2007-01-01

    Keywords: alcohol dehydrogenase, laboratory evolution, rational protein engineering, Pyrococcus furiosus, biocatalysis, characterization, computational design, thermostability.   Alcohol dehydrogeases (ADHs) catalyze the interconversion of alcohols, aldehydes and ketones. They display a wide variety of substrate specificities and are involved in an astonishingly wide range of metabolic processes, in all living organisms. Besides the scientific interest in ADHs, they are also attractive biocat...

  3. 嗜热乙醇杆菌中醛/醇脱氢酶的双启动子分析%The Promoter Analysis of the adhE Gene Encoding the Aldehyde/alcohol Dehydrogenase in Thermoanaerobacter ethanolicus

    Institute of Scientific and Technical Information of China (English)

    彭惠; 毛忠贵; 武国干; 邵蔚蓝

    2007-01-01

    克隆了嗜热乙醇杆菌(Thermoanaerobacter ethanolicus)中乙醇代谢的关键酶之一醛/醇脱氢酶(alcohol/acetaldehyde dehydrogenase,AdhE)基因的上游假定启动子序列,并进行了结构分析.结果表明,adhE的上游序列是启动子,能启动报告基因在大肠杆菌中持续表达.首次发现adhE的启动子序列中存在两个独立的启动子(P172和P37)和核糖体结合位点(SD172和SD37),分别都具有完整功能,但其活性均低于完整的启动子序列.由此推测嗜热乙醇杆菌中adhE的表达受这两个启动子协同调控.

  4. Mutations in ALDH1A3 cause microphthalmia.

    Science.gov (United States)

    Aldahmesh, M A; Khan, A O; Hijazi, H; Alkuraya, F S

    2013-08-01

    Microphthalmia is an important inborn error of eye development that can be associated with multisystem involvement. Anophthalmia is more severe and rarer. Single mutations in an expanding list of genes are known to cause this spectrum of anomaly. In one branch of a multiplex family with microphthalmia and anophthalmia, autozygome analysis excluded all known microphthalmia genes at the time of doing this study. Exome sequencing and autozygome filtration identified a novel homozygous variant in ALDH1A3. Subsequently, we identified another homozygous variant in 2 of the 10 probands with microphthalmia we specifically screened for mutations in ALDH1A3. Interestingly, the other branch of the original family was found to segregate anophthalmia/syndactyly with a novel homozygous SMOC1 variant. Our data support the very recent and independent identification of ALDH1A3 as a disease gene in microphthalmia. Locus heterogeneity should be considered in consanguineous families even for extremely rare phenotypes.

  5. Interaction between ALDH2*1*1 and DRD2/ANKK1 TaqI A1A1 genes may be associated with antisocial personality disorder not co-morbid with alcoholism.

    Science.gov (United States)

    Lu, Ru-Band; Lee, Jia-Fu; Huang, San-Yuan; Lee, Sheng-Yu; Chang, Yun-Hsuan; Kuo, Po-Hsiu; Chen, Shiou-Lan; Chen, Shih-Heng; Chu, Chun-Hsien; Lin, Wei-Wen; Wu, Pei-Lin; Ko, Huei-Chen

    2012-09-01

    Previous studies on acetaldehyde dehydrogenase 2 (ALDH2) focused on drinking behavior or alcoholism because the ALDH2*2 allele protects against the risk of developing alcoholism. The mechanism provides that the ALDH2 gene's protective effect is also involved in dopamine metabolism. The interaction of the ALDH2 gene with neurotransmitters, such as dopamine, is suggested to be related to alcoholism. Because alcoholism is often co-morbid with antisocial personality disorder (ASPD), previous association studies on antisocial alcoholism cannot differentiate whether those genes relate to ASPD with alcoholism or ASPD only. This study examined the influence of the interaction effect of the ALDH2*1*1, *1*2 or *2*2 polymorphisms with the dopamine 2 receptor (DRD2) Taq I polymorphism on ASPD. Our 541 Han Chinese male participants were classified into three groups: antisocial alcoholism (ASPD co-morbid with alcohol dependence, antisocial ALC; n = 133), ASPD without alcoholism (ASPD not co-morbid with alcohol dependence, antisocial non-ALC; n = 164) and community controls (healthy volunteers from the community; n = 244). Compared with healthy controls, individuals with the DRD2 A1/A1 and the ALDH2*1/*1 genotypes were at a 5.39 times greater risk for antisocial non-ALC than were those with other genotypes. Our results suggest that the DRD2/ANKK1 and ALDH2 genes interacted in the antisocial non-ALC group; a connection neglected in previous studies caused by not separating antisocial ALC from ASPD. Our study made this distinction and showed that these two genes may be associated ASPD without co-morbid alcoholism.

  6. Purification, characterization, and cDNA cloning of opine dehydrogenases from the polychaete rockworm Marphysa sanguinea.

    Science.gov (United States)

    Endo, Noriyuki; Kan-no, Nobuhiro; Nagahisa, Eizoh

    2007-06-01

    Alanopine dehydrogenase (AlDH) and three isoforms of strombine/alanopine dehydrogenase (St/AlDH) were purified from muscle tissue of the polychaete rockworm Marphysa sanguinea. The four enzymes, which can be distinguished by the isoelectric point, are monomeric 42 kDa proteins, possess similar pH-activity profiles, and display specificity for pyruvate and NAD(H). The three isoforms of St/AlDH show equivalent Km and Vmax for glycine and L-alanine and for D-strombine and meso-alanopine. Free amino acid levels in the muscle and D-strombine accumulation in vivo during muscle activity suggest that St/AlDHs function physiologically as StDH. AlDH shows specificity for L-alanine and meso-alanopine, but not for glycine or D-strombine. The amino acid sequences of AlDH and one of the St/AlDH isoforms were determined by a combination of amino acid sequence analysis and cDNA cloning. St/AlDH cDNA consisted of 1586 bp nucleotides that encode a 399-residue protein (43,346.70 Da), and AlDH cDNA consisted of 1587 bp nucleotides that encode a 399-residue protein (43,886.68 Da). The two amino acid sequences deduced from the cDNA displayed 67% amino acid identity, with greatest similarity to that of tauropine dehydrogenase from the polychaete Arabella iricolor. PMID:17350870

  7. 硝酸甘油对大鼠缺氧心肌细胞乙醛脱氢酶2 表达的影响%Effect of glyceryl trinitrate on expression of aldehyde dehydrogenase 2 in hypoxia-exposed rat cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    张应花; 孙爱军; 文小军; 王克强; 邹云增; 葛均波

    2010-01-01

    目的 探讨硝酸甘油(GTN)对大鼠缺氧心肌细胞凋亡的影响及其相关机制,为阐明长期使用GTN导致心脏不良事件的发病机制提供依据.方法 利用心肌细胞缺氧模型,将缺氧的正常细胞作为对照组,测定GTN作用1~3 d时心肌细胞的凋亡率以及乙醛脱氢酶2(ALDH2)基因和蛋白的表达.结果 ①1、10、100μmol/L的GTN作用1 d的心肌细胞凋亡均显著少于对照组(P值均<0.05),作用2、3 d的细胞凋亡数均显著高于作用1 d时(P值均<0.05).由此确定GTN的作用浓度是1μmol/L,作用时间是2 d.②不同浓度GTN作用1~3 d,ALDH2基因表达与心肌细胞凋亡率呈负相关(r=-0.658,P=0.028).③1μmol/LGTN作用2 d时的ALDH2蛋白表达为1.35±0.16,显著低于对照组的1.66±0.22(P<0.05);作用2、3 d时的ALDH2蛋白表达分别为1.35±0.16和0.33±0.27,均较作用1 d时显著下降(P值均<0.05).结论 ①GTN作用不同时间所起的作用不同:作用1 d,为心肌保护作用;作用2~3 d能引起心肌细胞凋亡增加,缺乏心肌保护作用.②GTN使用后ALDH2基因表达变化与心肌细胞凋亡呈负相关,可能与ALDH2对缺氧心肌细胞有保护作用有关.③GTN作用2~3 d时缺氧心肌细胞ALDH2 mRNA和蛋白水平下调,可能与ALDH2消耗有关.

  8. Incomplete penetrance of biallelic ALDH1A3 mutations.

    Science.gov (United States)

    Plaisancié, Julie; Brémond-Gignac, Dominique; Demeer, Bénédicte; Gaston, Véronique; Verloes, Alain; Fares-Taie, Lucas; Gerber, Sylvie; Rozet, Jean-Michel; Calvas, Patrick; Chassaing, Nicolas

    2016-04-01

    The formation of a properly shaped eye is a complex developmental event that requires the coordination of many induction processes and differentiation pathways. Microphthalmia and anophthalmia (MA) represent the most severe defects that can affect the ocular globe during embryonic development. When genetic, these ocular disorders exhibit large genetic heterogeneity and extreme variable expressivity. Around 20 monogenic diseases are known to be associated with MA as main phenotype and the penetrance of mutations is usually full in the patients. Some of these genes encode proteins involved in the vitamin A pathway, tightly regulated during eye development. One of those retinoic acid synthesis genes is ALDH1A3 and biallelic mutations in that gene have been recently found to lead to MA phenotype in patients. Interestingly, we report here the lack of ocular defect in a girl carrying the same homozygous mutation in the ALDH1A3 gene than the affected members of her family. Thus, this report brings new information for the phenotype-genotype correlation of ALDH1A3 mutations and raises important questions, especially in terms of genetic counselling given to the patients and their families. Furthermore, these data contribute to the more general understanding that we have for the complex genetic inheritance of these MA phenotypes. PMID:26873617

  9. Selective Enzymatic Reduction of Aldehydes

    Directory of Open Access Journals (Sweden)

    Patrizia Di Gennaro

    2006-05-01

    Full Text Available Highly selective enzymatic reductions of aldehydes to the corresponding alcohols was performed using an E. coli JM109 whole cell biocatalyst. A selective enzymatic method for the reduction of aldehydes could provide an eco-compatible alternative to chemical methods. The simplicity, fairly wide scope and the very high observed chemoselectivity of this approach are its most unique features.

  10. Alcohol, Aldehydes, Adducts and Airways.

    Science.gov (United States)

    Sapkota, Muna; Wyatt, Todd A

    2015-11-05

    Drinking alcohol and smoking cigarettes results in the formation of reactive aldehydes in the lung, which are capable of forming adducts with several proteins and DNA. Acetaldehyde and malondialdehyde are the major aldehydes generated in high levels in the lung of subjects with alcohol use disorder who smoke cigarettes. In addition to the above aldehydes, several other aldehydes like 4-hydroxynonenal, formaldehyde and acrolein are also detected in the lung due to exposure to toxic gases, vapors and chemicals. These aldehydes react with nucleophilic targets in cells such as DNA, lipids and proteins to form both stable and unstable adducts. This adduction may disturb cellular functions as well as damage proteins, nucleic acids and lipids. Among several adducts formed in the lung, malondialdehyde DNA (MDA-DNA) adduct and hybrid malondialdehyde-acetaldehyde (MAA) protein adducts have been shown to initiate several pathological conditions in the lung. MDA-DNA adducts are pre-mutagenic in mammalian cells and induce frame shift and base-pair substitution mutations, whereas MAA protein adducts have been shown to induce inflammation and inhibit wound healing. This review provides an insight into different reactive aldehyde adducts and their role in the pathogenesis of lung disease.

  11. Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

    DEFF Research Database (Denmark)

    Mills, Philippa B; Footitt, Emma J; Mills, Kevin A;

    2010-01-01

    sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound...

  12. Direct enzyme assay evidence confirms aldehyde reductase function of Ydr541cp and Ygl039wp from Saccharomyces cerevisiae

    Science.gov (United States)

    Aldehyde reductase gene ARI1 is a recently characterized member of intermediate subfamily under SDR (short-chain dehydrogenase/reductase) superfamily that revealed mechanisms of in situ detoxification of furfural and HMF for tolerance of Saccharomyces cerevisiae. Uncharacterized open reading frames ...

  13. Glucose-6-phosphate dehydrogenase

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003671.htm Glucose-6-phosphate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) is a type of ...

  14. aldh7a1 regulates eye and limb development in zebrafish.

    Directory of Open Access Journals (Sweden)

    Holly E Babcock

    Full Text Available Uveal coloboma is a potentially blinding congenital ocular malformation caused by failure of the optic fissure to close during development. Although mutations in numerous genes have been described, these account for a minority of cases, complicating molecular diagnosis and genetic counseling. Here we describe a key role of aldh7a1 as a gene necessary for normal eye development. We show that morpholino knockdown of aldh7a1 in zebrafish causes uveal coloboma and misregulation of nlz1, another known contributor to the coloboma phenotype, as well as skeletal abnormalities. Knockdown of aldh7a1 leads to reduced cell proliferation in the optic cup of zebrafish, delaying the approximation of the edges of the optic fissure. The aldh7a1 morphant phenotype is partially rescued by co-injection of nlz1 mRNA suggesting that nlz1 is functionally downstream of aldh7a1 in regulating cell proliferation in the optic cup. These results support a role of aldh7a1 in ocular development and skeletal abnormalities in zebrafish.

  15. 高粱耐逆基因SbALDH7的克隆与表达分析%Isolation and Expressing Analysis of A Stress Tolerance Gene SbALDH7in Sorghum bicolor

    Institute of Scientific and Technical Information of China (English)

    陈加敏; 朱承慧

    2013-01-01

    The sequence features and expression patterns of SbALDH7 were studied in Sorghum bicolor. The cDNA of SbALDH7 was cloned by RT-PCR. The structure features was analyzed by bioinformatics software. The expression patterns of the gene were investigated using Semi-quantitive RT-PCR in different tissues under different stress. The result showed that SbALDH7 included 13 introns and encoded a protein sequence with 509 amino acids. The protein deduced from SbALDH7 possesses typical characteristics of members of the ALDH7 protein family. Transcript levels of the SbALDH7 genes were upregulated by PEG, NaCl, ABA and 4℃. In PEG osmotic stress, transcript levels of the SbALDH7 gene were higher in leaf and culm than in root. There was no difference in SbALDH7 protein sequences of six sorghum varieties, which had remarkably different drought tolerance. However, there was remarkable positive correlation between seedling drought resistance of varieties and transcript levels of SbALDH7. The results showed expression of SbALDH7 was important for drought tolerance of Sorghum bicolor. SbALDH7 had typical structure features of ALDH protein family, and it played an important role during the process of stress response. SbALDH7 could be used as a target gene for crop genetic improvement.%旨在研究高粱(Sorghum bicolor)中的醛脱氢酶基因SbALDH7的序列信息和表达分析.通过PCR和RT-PCR方法,从高粱中克隆SbALDH7基因及其cDNA全长序列.通过网络软件,聚类分析SbALDH7的序列特征,利用半定量RT-PCR,研究其在不同组织和胁迫条件下的表达谱.结果表明:SbALDH7基因含13个内含子,共编码509个氨基酸,其编码的氨基酸序列具有典型的ALDH7结构域特征.SbALDH7的表达受到PEG、Nacl、ABA和低温等胁迫环境诱导上调.组织特异性表达分析显示,在PEG渗透胁迫环境下,SbALDH7在茎、叶中的表达量显著高于根中的表达量.抗旱性有显著差异的6个高粱品种的SbALDH7蛋白序列无差

  16. GRE2 from Scheffersomyces stipitis as an aldehyde reductase contributes tolerance to aldehyde inhibitors derived from lignocellulosic biomass.

    Science.gov (United States)

    Wang, Xu; Ma, Menggen; Liu, Z Lewis; Xiang, Quanju; Li, Xi; Liu, Na; Zhang, Xiaoping

    2016-08-01

    Scheffersomyces (Pichia) stipitis is one of the most promising yeasts for industrial bioethanol production from lignocellulosic biomass. S. stipitis is able to in situ detoxify aldehyde inhibitors (such as furfural and 5-hydroxymethylfurfural (HMF)) to less toxic corresponding alcohols. However, the reduction enzymes involved in this reaction remain largely unknown. In this study, we reported that an uncharacterized open reading frame PICST_72153 (putative GRE2) from S. stipitis was highly induced in response to furfural and HMF stresses. Overexpression of this gene in Saccharomyces cerevisiae improved yeast tolerance to furfural and HMF. GRE2 was identified as an aldehyde reductase which can reduce furfural to FM with either NADH or NADPH as the co-factor and reduce HMF to FDM with NADPH as the co-factor. This enzyme can also reduce multiple aldehydes to their corresponding alcohols. Amino acid sequence analysis indicated that it is a member of the subclass "intermediate" of the short-chain dehydrogenase/reductase (SDR) superfamily. Although GRE2 from S. stipitis is similar to GRE2 from S. cerevisiae in a three-dimensional structure, some differences were predicted. GRE2 from S. stipitis forms loops at D133-E137 and T143-N145 locations with two α-helices at E154-K157 and E252-A254 locations, different GRE2 from S. cerevisiae with an α-helix at D133-E137 and a β-sheet at T143-N145 locations, and two loops at E154-K157 and E252-A254 locations. This research provided guidelines for the study of other SDR enzymes from S. stipitis and other yeasts on tolerant mechanisms to aldehyde inhibitors derived from lignocellulosic biomass. PMID:27003269

  17. Synthesis of 5'-Aldehyde Oligonucleotide.

    Science.gov (United States)

    Lartia, Rémy

    2016-01-01

    Synthesis of oligonucleotide ending with an aldehyde functional group at their 5'-end (5'-AON) is possible for both DNA (5'-AODN) and RNA (5'-AORN) series irrespectively of the nature of the last nucleobase. The 5'-alcohol of on-support ODN is mildly oxidized under Moffat conditions. Transient protection of the resulting aldehyde by N,N'-diphenylethylenediamine derivatives allows cleavage, deprotection, and RP-HPLC purification of the protected 5'-AON. Finally, 5'-AON is deprotected by usual acetic acid treatment. In the aggregates, 5'-AON can be now synthesized and purified as routinely as non-modified ODNs, following procedures similar to the well-known "DMT-On" strategy. PMID:26967469

  18. Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells.

    Science.gov (United States)

    Liu, Jing; Xiao, Zhijie; Wong, Sunny Kit-Man; Tin, Vicky Pui-Chi; Ho, Ka-Yan; Wang, Junwen; Sham, Mai-Har; Wong, Maria Pik

    2013-10-01

    Limited improvement in long term survival of lung cancer patients has been achieved by conventional chemotherapy or targeted therapy. To explore the potentials of tumor initiating cells (TIC)-directed therapy, it is essential to identify the cell targets and understand their maintenance mechanisms. We have analyzed the performance of ALDH/CD44 co-expression as TIC markers and treatment targets of lung cancer using well-validated in vitro and in vivo analyses in multiple established and patient-derived lung cancer cells. The ALDH(hi)CD44(hi) subset showed the highest enhancement of stem cell phenotypic properties compared to ALDH(hi)CD44(lo), ALDH(lo)CD44(hi), ALDH(lo)CD44(lo) cells and unsorted controls. They showed higher invasion capacities, pluripotency genes and epithelial-mesenchymal transition transcription factors expression, lower intercellular adhesion protein expression and higher G2/M phase cell cycle fraction. In immunosuppressed mice, the ALDH(hi)CD44(hi)xenografts showed the highest tumor induction frequency, serial transplantability, shortest latency, largest volume and highest growth rates. Inhibition of sonic Hedgehog and Notch developmental pathways reduced ALDH+CD44+ compartment. Chemotherapy and targeted therapy resulted in higher AALDH(hi)CD44(hi) subset viability and ALDH(lo)CD44(lo) subset apoptosis fraction. ALDH inhibition and CD44 knockdown led to reduced stemness gene expression and sensitization to drug treatment. In accordance, clinical lung cancers containing a higher abundance of ALDH and CD44-coexpressing cells was associated with lower recurrence-free survival. Together, results suggested theALDH(hi)CD44(hi)compartment was the cellular mediator of tumorigenicity and drug resistance. Further investigation of the regulatory mechanisms underlying ALDH(hi)CD44(hi)TIC maintenance would be beneficial for the development of long term lung cancer control.

  19. Biological Functions of ALDH1-positive Cancer Cells in the A549 Lung Cancer Cell Line%肺癌A549细胞株中ALDH1+细胞的生物学功能研究

    Institute of Scientific and Technical Information of China (English)

    邹爱梅; 吴爱兵; 黄维甄; 张金标; 谢剑明; 李荣; 罗荣城

    2011-01-01

    目的:探讨肺癌A549细胞株中具有肿瘤干细胞特性的ALDH1+细胞的生物学功能特性.方法:运用流式细胞仪分选肺癌A549细胞株中ALDH1+细胞,并通过肿瘤球培养、MTT实验、平板克隆、Transwell小室迁移实验、裸鼠体内成瘤实验来验证ALDH1+细胞的自我更新、增殖克隆、迁移及致瘤能力.结果:ALDH1+ A549细胞的肿瘤球形成能力、增殖克隆、迁移和体内成瘤能力明显高于ALDH1- A549细胞和未经分选的A549细胞.结论:A549细胞株中ALDH1+ A549细胞具有自我更新、增殖、迁移和高致瘤能力的肿瘤干细胞特性,ALDH1可作为分选肺癌肿瘤干细胞的标志物.%Objective: To investigate the biological functions of the ALDH1-positive cancer cells exhibiting the characteristics of a cancer stem cell in the A549 lung cancer cell line.Methods: Fluorescence-activated cell sorting analysis was used to differentiate between the ALDH1-positive and ALDH1-negative cancer cells in an A549 lung cancer cell line.Tumor sphere cultivation, MTT, clonogenicity, and in vitro transwell assays as well as tumor initiation in vivo were used to compare the self-renewing, proliferative, clonogenic, and invasive abilities as well as the tumorigenicity between the ALDH1-positive, ALDH1-negative, and unsorted A549 cells.Results: The self-renewing, proliferative, clonogenic, and invasive abilities as well as the tumorigenicity of the ALDH1-positive cancer cells in the A549 lung cancer cell line were higher than those of the ALDH1-negative and unsorted A549 cells.Conclusion: The ALDH1-positive cancer cells in the A549 lung cancer cell line possess the characteristics of cancer stem cells and may be used as NSCLCSC-associated tumor markers.

  20. GenBank blastx search result: AK061794 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061794 001-039-F11 AY566467.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*1 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 1e-86 +1 ...

  1. GenBank blastx search result: AK119320 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119320 001-130-H10 AY566469.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*3 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 1e-156 +1 ...

  2. GenBank blastx search result: AK060757 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060757 001-032-H04 AY566468.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*2 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 9e-43 +1 ...

  3. GenBank blastx search result: AK107309 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107309 002-126-D05 AY566469.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*3 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 1e-143 +1 ...

  4. GenBank blastx search result: AK060461 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060461 001-012-B10 AY566467.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*1 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 1e-80 +1 ...

  5. GenBank blastx search result: AK061794 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061794 001-039-F11 AY566468.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*2 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 1e-86 +1 ...

  6. GenBank blastx search result: AK060461 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060461 001-012-B10 AY566469.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*3 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 4e-80 +1 ...

  7. GenBank blastx search result: AK119320 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119320 001-130-H10 AY566468.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*2 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 1e-156 +1 ...

  8. GenBank blastx search result: AK107309 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107309 002-126-D05 AY566468.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*2 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 1e-143 +1 ...

  9. GenBank blastx search result: AK061794 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061794 001-039-F11 AY566469.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*3 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 1e-86 +1 ...

  10. GenBank blastx search result: AK119320 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119320 001-130-H10 AY566467.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*1 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 1e-156 +1 ...

  11. GenBank blastx search result: AK060461 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060461 001-012-B10 AY566468.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*2 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 1e-80 +1 ...

  12. GenBank blastx search result: AK060757 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060757 001-032-H04 AY566469.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*3 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 9e-43 +1 ...

  13. GenBank blastx search result: AK107309 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107309 002-126-D05 AY566467.1 Rattus norvegicus mitochondrial aldehyde dehydrogenase precursor (Aldh...2) mRNA, Aldh2*1 allele, partial cds; nuclear gene for mitochondrial product.|ROD ROD 1e-143 +1 ...

  14. Microsphere coated substrate containing reactive aldehyde groups

    Science.gov (United States)

    Rembaum, Alan (Inventor); Yen, Richard C. K. (Inventor)

    1984-01-01

    A synthetic organic resin is coated with a continuous layer of contiguous, tangential, individual microspheres having a uniform diameter preferably between 100 Angstroms and 2000 Angstroms. The microspheres are an addition polymerized polymer of an unsaturated aldehyde containing 4 to 20 carbon atoms and are covalently bonded to the substrate by means of high energy radiation grafting. The microspheres contain reactive aldehyde groups and can form conjugates with proteins such as enzymes or other aldehyde reactive materials.

  15. Synthesis and accumulation of aromatic aldehydes in an engineered strain of Escherichia coli.

    Science.gov (United States)

    Kunjapur, Aditya M; Tarasova, Yekaterina; Prather, Kristala L J

    2014-08-20

    Aromatic aldehydes are useful in numerous applications, especially as flavors, fragrances, and pharmaceutical precursors. However, microbial synthesis of aldehydes is hindered by rapid, endogenous, and redundant conversion of aldehydes to their corresponding alcohols. We report the construction of an Escherichia coli K-12 MG1655 strain with reduced aromatic aldehyde reduction (RARE) that serves as a platform for aromatic aldehyde biosynthesis. Six genes with reported activity on the model substrate benzaldehyde were rationally targeted for deletion: three genes that encode aldo-keto reductases and three genes that encode alcohol dehydrogenases. Upon expression of a recombinant carboxylic acid reductase in the RARE strain and addition of benzoate during growth, benzaldehyde remained in the culture after 24 h, with less than 12% conversion of benzaldehyde to benzyl alcohol. Although individual overexpression results demonstrated that all six genes could contribute to benzaldehyde reduction in vivo, additional experiments featuring subset deletion strains revealed that two of the gene deletions were dispensable under the conditions tested. The engineered strain was next investigated for the production of vanillin from vanillate and succeeded in preventing formation of the byproduct vanillyl alcohol. A pathway for the biosynthesis of vanillin directly from glucose was introduced and resulted in a 55-fold improvement in vanillin titer when using the RARE strain versus the wild-type strain. Finally, synthesis of the chiral pharmaceutical intermediate L-phenylacetylcarbinol (L-PAC) was demonstrated from benzaldehyde and glucose upon expression of a recombinant mutant pyruvate decarboxylase in the RARE strain. Beyond allowing accumulation of aromatic aldehydes as end products in E. coli, the RARE strain expands the classes of chemicals that can be produced microbially via aldehyde intermediates. PMID:25076127

  16. Declinol, a Complex Containing Kudzu, Bitter Herbs (Gentian, Tangerine Peel) and Bupleurum, Significantly Reduced Alcohol Use Disorders Identification Test (AUDIT) Scores in Moderate to Heavy Drinkers: A Pilot Study

    OpenAIRE

    Kushner, Steven; HAN, DAVID; Oscar-Berman, Marlene; B. William Downs; Margaret A. Madigan; Giordano, John; Beley, Thomas; Jones, Scott; Barh, Debmayla; Simpatico, Thomas; Dushaj, Kristina; Lohmann, Raquel; Braverman, Eric R; Schoenthaler, Stephen; Ellison, David

    2013-01-01

    It is well established that inherited human aldehyde dehydrogenase 2 (ALDH-2) deficiency reduces the risk for alcoholism. Kudzu plants and extracts have been used for 1,000 years in traditional Chinese medicine to treat alcoholism. Kudzu contains daidzin, which inhibits ALDH-2 and suppresses heavy drinking in rodents. Decreased drinking due to ALDH-2 inhibition is attributed to aversive properties of acetaldehyde accumulated during alcohol consumption. However not all of the anti-alcohol prop...

  17. Severe congenital cutis laxa with cardiovascular manifestations due to homozygous deletions in ALDH18A1

    NARCIS (Netherlands)

    Fischer, B.; Callewaert, B.; Schroter, P.; Coucke, P.J.; Schlack, C.; Ott, C.E.; Morroni, M.; Homann, W.; Mundlos, S.; Morava, E.; Ficcadenti, A.; Kornak, U.

    2014-01-01

    Autosomal recessive cutis laxa (ARCL) type 2 constitutes a heterogeneous group of diseases mainly characterized by lax and wrinkled skin, skeletal anomalies, and a variable degree of intellectual disability. ALDH18A1-related ARCL is the most severe form within this disease spectrum. Here we report o

  18. ALDH maintains the stemness of lung adenoma stem cells by suppressing the Notch/CDK2/CCNE pathway.

    Directory of Open Access Journals (Sweden)

    Zhongjun Li

    Full Text Available To evaluate the expression of ALDH1A1 in lung adenoma stem cells (LASCs and maintenance of their stemness through the Notch pathway.LASCs (A549s were isolated from lung adenoma cells (A549 and identified by their coexpression of CD133 and CD326 and their capacity formulti-directional differentiation. Expression of ALDH1A1 in A549 and A549s cells were evaluated by Real-time PCR. Effects of ALDH1A1 upregulation in A549 cells and its downregulation in A549s cells on the clonogenicity and cell cycle were assessed by colony-forming unit assay. Moreover, the effects of ALDH1A1 on the Notch pathway, and thus on the cell cycle, were studied.A549s cells were successfully isolated and identified.ALDH1A1expression was significantly higher in A549s than in A549 cells. Clonogenicity was significantly decreased in A549s cells treated with ALDH1A1 siRNA. Duration of the G1 stage of the cell cycle increased after ALDH1A1 was overexpressed, or decreased with ALDH1A1 siRNA. ALDH1A1, Notch1, -2, and -3, CDK2, and CCNE1 expression levels were higher in A549s cells than in A549 cells. Expression of Notch1, -2, and -3, CDK2, and CCNE1 was significantly decreased by upregulation of ALDH1A1 in A549 cells, but increased by its interruption in A549s cells. When Notch3 or CDK2 expression was downregulated, the expression levels of ALDH1A1, Notch1, -2, and -3, CDK2, and CCNE1 were reduced in all cell types.ALDH1A1 expression improved clonogenicity and inhibited the cell cycle, maintaining the stemness of the A549s cells; this may involve suppression of the Notch/CDK2/Cyclin pathway.

  19. Interaction of carbohydrates with alcohol dehydrogenase: Effect on enzyme activity.

    Science.gov (United States)

    Jadhav, Swati B; Bankar, Sandip B; Granström, Tom; Ojamo, Heikki; Singhal, Rekha S; Survase, Shrikant A

    2015-09-01

    Alcohol dehydrogenase was covalently conjugated with three different oxidized carbohydrates i.e., glucose, starch and pectin. All the carbohydrates inhibited the enzyme. The inhibition was studied with respect to the inhibition rate constant, involvement of thiol groups in the binding, and structural changes in the enzyme. The enzyme activity decreased to half of its original activity at the concentration of 2 mg/mL of pectin, 4 mg/mL of glucose and 10 mg/mL of starch within 10 min at pH 7. This study showed oxidized pectin to be a potent inhibitor of alcohol dehydrogenase followed by glucose and starch. Along with the aldehyde-amino group interaction, thiol groups were also involved in the binding between alcohol dehydrogenase and carbohydrates. The structural changes occurring on binding of alcohol dehydrogenase with oxidized carbohydrates was also confirmed by fluorescence spectrophotometry. Oxidized carbohydrates could thus be used as potential inhibitors of alcohol dehydrogenase.

  20. Efficient and Highly Aldehyde Selective Wacker Oxidation

    KAUST Repository

    Teo, Peili

    2012-07-06

    A method for efficient and aldehyde-selective Wacker oxidation of aryl-substituted olefins using PdCl 2(MeCN) 2, 1,4-benzoquinone, and t-BuOH in air is described. Up to a 96% yield of aldehyde can be obtained, and up to 99% selectivity can be achieved with styrene-related substrates. © 2012 American Chemical Society.

  1. Alcohol and the Asian Glow

    OpenAIRE

    Young, Brian

    1999-01-01

    Facial flushing is a common hypersensitivity reaction that may be observed in many Asians following low to moderate alcohol consumption. Flushing can be accompanied by other symptoms such as tachycardia, nausea, and dizziness. Recent studies have shown that this flushing reaction is due to the presence of ALDH2*2, an inactive allele for the alcohol dehydrogenase gene found in approximately 50% of Asians. Aldehyde dehydrogenase (ALDH) is an important enzyme in alcohol metabolism, and deficienc...

  2. Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer.

    Science.gov (United States)

    Ayub, Tiyasha H; Keyver-Paik, Mignon-Denise; Debald, Manuel; Rostamzadeh, Babak; Thiesler, Thore; Schröder, Lars; Barchet, Winfried; Abramian, Alina; Kaiser, Christina; Kristiansen, Glen; Kuhn, Walther; Kübler, Kirsten

    2015-06-30

    Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes. PMID:25999351

  3. ALDH1在乳腺UDH、ADH、IDC中的表达及意义%The Expression and Significance of ALDH1 in Usual Ductal Hyperplasia (UDH), Atypical Ductal Hyperplasia (ADH) and Infiltrative Ductal Carcino-ma (IDC)

    Institute of Scientific and Technical Information of China (English)

    郭钰; 卫建平

    2014-01-01

    Objective To investigate the expression of ALDH1 in usual ductal hyperplasia, atypical ductal hyperplasia and infiltra-tive ductal carcinoma and its clinical significance. Methods Immunohistochemistry method was used to detect the expression of ALDH1 in the normal mammary gland of 30 cases and mammary gland ductal disease of 90 cases of patients. Results The positive expression rate of ALDH1 in normal mammary gland, usual ductal hyperplasia, atypical ductal hyperplasia and infiltrative ductal carcinoma was 0%, 23.3%, 23.3%, 60%, respectively. Conclusion The positive rate of ALDH1 in patients with infiltrative ductal carcinoma was significantly higher than that in normal mammary gland and other mammary gland diseases, which suggests that the positive expression of ALDH1 has a certain relationship with the evolution of the mammary gland hyperplasia to mammary gland cancer and the prognosis of the disease.%目的:探讨ALDH1在乳腺普通导管增生、非典型导管上皮增生以及浸润性导管癌中表达及其临床意义。方法采用免疫组织化学方法对30例正常乳腺及90例乳腺导管疾病患者的ALDH1的表达进行测定。结果 ALDH1在正常、乳腺普通导管增生、不典型导管上皮增生以及浸润性导管癌中的阳性表达率为:0%、23.3%、23.3%、60%。结论乳腺浸润性导管癌患者的ALDH1的阳性率明显高于正常乳腺及其它乳腺导管疾病,提示ALDH1的阳性表达与乳腺增生至乳腺癌变的演进,且与疾病的预后有一定的关系。

  4. Glucose-6-phosphate dehydrogenase deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000528.htm Glucose-6-phosphate dehydrogenase deficiency To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a condition ...

  5. Crystal structure of quinone-dependent alcohol dehydrogenase from Pseudogluconobacter saccharoketogenes. A versatile dehydrogenase oxidizing alcohols and carbohydrates.

    Science.gov (United States)

    Rozeboom, Henriëtte J; Yu, Shukun; Mikkelsen, Rene; Nikolaev, Igor; Mulder, Harm J; Dijkstra, Bauke W

    2015-12-01

    The quinone-dependent alcohol dehydrogenase (PQQ-ADH, E.C. 1.1.5.2) from the Gram-negative bacterium Pseudogluconobacter saccharoketogenes IFO 14464 oxidizes primary alcohols (e.g. ethanol, butanol), secondary alcohols (monosaccharides), as well as aldehydes, polysaccharides, and cyclodextrins. The recombinant protein, expressed in Pichia pastoris, was crystallized, and three-dimensional (3D) structures of the native form, with PQQ and a Ca(2+) ion, and of the enzyme in complex with a Zn(2+) ion and a bound substrate mimic were determined at 1.72 Å and 1.84 Å resolution, respectively. PQQ-ADH displays an eight-bladed β-propeller fold, characteristic of Type I quinone-dependent methanol dehydrogenases. However, three of the four ligands of the Ca(2+) ion differ from those of related dehydrogenases and they come from different parts of the polypeptide chain. These differences result in a more open, easily accessible active site, which explains why PQQ-ADH can oxidize a broad range of substrates. The bound substrate mimic suggests Asp333 as the catalytic base. Remarkably, no vicinal disulfide bridge is present near the PQQ, which in other PQQ-dependent alcohol dehydrogenases has been proposed to be necessary for electron transfer. Instead an associated cytochrome c can approach the PQQ for direct electron transfer.

  6. New studies of the alcohol dehydrogenase cline in D. melanogaster from Mexico.

    Science.gov (United States)

    Pipkin, S B; Franklin-Springer, E; Law, S; Lubega, S

    1976-01-01

    An altitudinal cline of frequencies of alcohol dehydrogenase alleles occurs in D. melanogaster populations of southeastern Mexico. A similar cline of two aldehyde oxidase alleles is present, but frequencies of esterase-6 alleles are not distributed clinically. Collections were made from small dispersed populations. Some gene flow occurred throughout the lowlands according to the distribution of two moderately endemic autosomal inversions and five previously described inversions. The clines are believed dependent on a limited gene flow between temperature races of D. melanogaster.

  7. Structure of a bifunctional alcohol dehydrogenase involved in bioethanol generation in Geobacillus thermoglucosidasius.

    Science.gov (United States)

    Extance, Jonathan; Crennell, Susan J; Eley, Kirstin; Cripps, Roger; Hough, David W; Danson, Michael J

    2013-10-01

    Bifunctional alcohol/aldehyde dehydrogenase (ADHE) enzymes are found within many fermentative microorganisms. They catalyse the conversion of an acyl-coenzyme A to an alcohol via an aldehyde intermediate; this is coupled to the oxidation of two NADH molecules to maintain the NAD(+) pool during fermentative metabolism. The structure of the alcohol dehydrogenase (ADH) domain of an ADHE protein from the ethanol-producing thermophile Geobacillus thermoglucosidasius has been determined to 2.5 Å resolution. This is the first structure to be reported for such a domain. In silico modelling has been carried out to generate a homology model of the aldehyde dehydrogenase domain, and this was subsequently docked with the ADH-domain structure to model the structure of the complete ADHE protein. This model suggests, for the first time, a structural mechanism for the formation of the large multimeric assemblies or `spirosomes' that are observed for this ADHE protein and which have previously been reported for ADHEs from other organisms.

  8. 40 CFR 721.5762 - Aromatic aldehyde phenolic resin (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Aromatic aldehyde phenolic resin... Specific Chemical Substances § 721.5762 Aromatic aldehyde phenolic resin (generic). (a) Chemical substance... aromatic aldehyde phenolic resin (PMN P-01-573) is subject to reporting under this section for...

  9. Pyruvate Dehydrogenase Kinase 4

    OpenAIRE

    Cadoudal, Thomas; Distel, Emilie; Durant, Sylvie; Fouque, Françoise; Blouin, Jean-Marc; Collinet, Martine; Bortoli, Sylvie; Forest, Claude; Benelli, Chantal

    2008-01-01

    OBJECTIVE—Pyruvate dehydrogenase complex (PDC) serves as the metabolic switch between glucose and fatty acid utilization. PDC activity is inhibited by PDC kinase (PDK). PDC shares the same substrate, i.e., pyruvate, as glyceroneogenesis, a pathway controlling fatty acid release from white adipose tissue (WAT). Thiazolidinediones activate glyceroneogenesis. We studied the regulation by rosiglitazone of PDK2 and PDK4 isoforms and tested the hypothesis that glyceroneogenesis could be controlled ...

  10. ALDH/CD44 identifies uniquely tumorigenic cancer stem cells in salivary gland mucoepidermoid carcinomas.

    Science.gov (United States)

    Adams, April; Warner, Kristy; Pearson, Alexander T; Zhang, Zhaocheng; Kim, Hong Sun; Mochizuki, Daiki; Basura, Gregory; Helman, Joseph; Mantesso, Andrea; Castilho, Rogério M; Wicha, Max S; Nör, Jacques E

    2015-09-29

    A small sub-population of cells characterized by increased tumorigenic potential, ability to self-renew and to differentiate into cells that make up the tumor bulk, has been characterized in some (but not all) tumor types. These unique cells, namedcancer stem cells, are considered drivers of tumor progression in these tumors. The purpose of this work is to understand if cancer stem cells play a functional role in the tumorigenesis of salivary gland mucoepidermoid carcinomas. Here, we investigated the expression of putative cancer stem cell markers (ALDH, CD10, CD24, CD44) in primary human mucoepidermoid carcinomas by immunofluorescence, in vitro salisphere assays, and in vivo tumorigenicity assays in immunodeficient mice. Human mucoepidermoid carcinoma cells (UM-HMC-1, UM-HMC-3A, UM-HMC-3B) sorted for high levels of ALDH activity and CD44 expression (ALDHhighCD44high) consistently formed primary and secondary salispheres in vitro, and showed enhanced tumorigenic potential in vivo (defined as time to tumor palpability, tumor growth after palpability), when compared to ALDHlowCD44low cells. Cells sorted for CD10/CD24, and CD10/CD44 showed varying trends of salisphere formation, but consistently low in vivo tumorigenic potential. And finally, cells sorted for CD44/CD24 showed inconsistent results in salisphere formation and tumorigenic potential assays when different cell lines were evaluated. Collectively, these data demonstrate that salivary gland mucoepidermoid carcinomas contain a small population of cancer stem cells with enhanced tumorigenic potential and that are characterized by high ALDH activity and CD44 expression. These results suggest that patients with mucoepidermoid carcinoma might benefit from therapies that ablate these highly tumorigenic cells.

  11. Subchronic exposure to ethyl tertiary butyl ether resulting in genetic damage in Aldh2 knockout mice.

    Science.gov (United States)

    Weng, Zuquan; Suda, Megumi; Ohtani, Katsumi; Mei, Nan; Kawamoto, Toshihiro; Nakajima, Tamie; Wang, Rui-Sheng

    2013-09-15

    Ethyl tertiary butyl ether (ETBE) is biofuel additive recently used in Japan and some other countries. Limited evidence shows that ETBE has low toxicity. Acetaldehyde (AA), however, as one primary metabolite of ETBE, is clearly genotoxic and has been considered to be a potential carcinogen. The aim of this study was to evaluate the effects of ALDH2 gene on ETBE-induced genotoxicity and metabolism of its metabolites after inhalation exposure to ETBE. A group of wild-type (WT) and Aldh2 knockout (KO) C57BL/6 mice were exposed to 500ppm ETBE for 1-6h, and the blood concentrations of ETBE metabolites, including AA, tert-butyl alcohol and 2-methyl-1,2-propanediol, were measured. Another group of mice of WT and KO were exposed to 0, 500, 1750, or 5000ppm ETBE for 6h/day with 5 days per weeks for 13 weeks. Genotoxic effects of ETBE in these mice were measured by the alkaline comet assay, 8-hydroxyguanine DNA-glycosylase modified comet assay and micronucleus test. With short-term exposure to ETBE, the blood concentrations of all the three metabolites in KO mice were significantly higher than the corresponding concentrations of those in WT mice of both sexes. After subchronic exposure to ETBE, there was significant increase in DNA damage in a dose-dependent manner in KO male mice, while only 5000ppm exposure significantly increased DNA damage in male WT mice. Overall, there was a significant sex difference in genetic damage in both genetic types of mice. These results showed that ALDH2 is involved in the detoxification of ETBE and lack of enzyme activity may greatly increase the sensitivity to the genotoxic effects of ETBE, and male mice were more sensitive than females. PMID:23810710

  12. Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis

    OpenAIRE

    Macgregor, Stuart; Lind, Penelope A; Bucholz, Kathleen K.; Hansell, Narelle K.; Madden, Pamela A. F.; Richter, Melinda M; Montgomery, Grant W.; Martin, Nicholas G.; Heath, Andrew C.; John B Whitfield

    2008-01-01

    Alcohol dependence (AD) is a complex disorder with environmental and genetic origins. The role of two genetic variants in ALDH2 and ADH1B in AD risk has been extensively investigated. This study tested for associations between nine polymorphisms in ALDH2 and 41 in the seven ADH genes, and alcohol-related flushing, alcohol use and dependence symptom scores in 4597 Australian twins. The vast majority (4296) had consumed alcohol in the previous year, with 547 meeting DSM-IIIR criteria for AD. Th...

  13. Ethanol and Acetaldehyde After Intraperitoneal Administration to Aldh2-Knockout Mice-Reflection in Blood and Brain Levels.

    Science.gov (United States)

    Jamal, Mostofa; Ameno, Kiyoshi; Tanaka, Naoko; Ito, Asuka; Takakura, Ayaka; Kumihashi, Mitsuru; Kinoshita, Hiroshi

    2016-05-01

    This paper reports, for the first time, on the analysis of ethanol (EtOH) and acetaldehyde (AcH) concentrations in the blood and brains of Aldh2-knockout (Aldh2-KO) and C57B6/6J (WT) mice. Animals were administrated EtOH (1.0, 2.0 or 4.0 g/kg) or 4-methylpyrazole (4-MP, 82 mg/kg) plus AcH (50, 100 or 200 mg/kg) intraperitoneally. During the blood tests, samples from the orbital sinus of the eye were collected. During the brain tests, dialysates were collected every 5 min (equal to a 15 µl sample) from the striatum using in vivo brain microdialysis. Samples were collected at 5, 10, 15, 20, 25, 30 and 60 min intervals post-EtOH and -AcH injection, and then analyzed by head-space GC. In the EtOH groups, high AcH levels were found in the blood and brains of Aldh2-KO mice, while only small traces of AcH were seen in the blood and brains of WT mice. No significant differences in EtOH levels were observed between the WT and the Aldh2-KO mice for either the EtOH dose. EtOH concentrations in the brain were comparable to the EtOH concentrations in the blood, but the AcH concentrations in the brain were four to five times lower compared to the AcH concentrations in the blood. In the AcH groups, high AcH levels were found in both WT and Aldh2-KO mice. Levels reached a sharp peak at 5 min and then quickly declined for 60 min. Brain AcH concentrations were almost equal to the concentrations found in the blood, where the AcH concentrations were approximately two times higher in the Aldh2-KO mice than in the WT mice, both in the blood and the brain. Our results suggest that systemic EtOH and AcH administration can cause a greater increase in AcH accumulation in the blood and brains of Aldh2-KO mice, where EtOH concentrations in the Aldh2-KO mice were comparable to the EtOH concentrations in the WT mice. Furthermore, detection of EtOH and AcH in the blood and brain was found to be dose-dependent in both genotypes. PMID:26646001

  14. Allylation of Aromatic Aldehyde under Microwave Irradiation

    Institute of Scientific and Technical Information of China (English)

    ZHANG,Yu-Mei; JIA,Xue-Feng; WANG,Jin-Xian

    2004-01-01

    @@ Allylation of carbonyl compounds is one of the most interesting processes for the preparation of homoallylic alcohols. Over the past few decades, many reagents have been developed for such reactions[1~3]. In this paper, we first report allylic zinc reagent 1, which can be prepared from zinc dust and allyl bromide conveniently in THF, and reacted with aromatic aldehyde to give homo-allylic alcohols under microwave irradiation.

  15. Expression, crystallization and preliminary X-ray crystallographic analysis of alcohol dehydrogenase (ADH) from Kangiella koreensis.

    Science.gov (United States)

    Ngo, Ho-Phuong-Thuy; Hong, Seung-Hye; Hong, Myoung-Ki; Pham, Tan-Viet; Oh, Deok-Kun; Kang, Lin-Woo

    2013-09-01

    Alcohol dehydrogenases (ADHs) are a group of dehydrogenase enzymes that facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of NAD(+) to NADH. In bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD(+). The adh gene from Kangiella koreensis was cloned and the protein (KkADH) was expressed, purified and crystallized. A KkADH crystal diffracted to 2.5 Å resolution and belonged to the monoclinic space group P2(1), with unit-cell parameters a = 94.1, b = 80.9, c = 115.6 Å, β = 111.9°. Four monomers were present in the asymmetric unit, with a corresponding VM of 2.55 Å(3) Da(-1) and a solvent content of 51.8%.

  16. Affinity chromatography of nicotinamide-adenine dinucleotide-linked dehydrogenases on immobilized derivatives of the dinucleotide.

    Science.gov (United States)

    Barry, S; O'Carra, P

    1973-12-01

    1. Three established methods for immobilization of ligands through primary amino groups promoted little or no attachment of NAD(+) through the 6-amino group of the adenine residue. Two of these methods (coupling to CNBr-activated agarose and to carbodi-imide-activated carboxylated agarose derivatives) resulted instead in attachment predominantly through the ribosyl residues. Other immobilized derivatives were prepared by azolinkage of NAD(+) (probably through the 8 position of the adenine residue) to a number of different spacer-arm-agarose derivatives. 2. The effectiveness of these derivatives in the affinity chromatography of a variety of NAD-linked dehydrogenases was investigated, applying rigorous criteria to distinguish general or non-specific adsorption effects from truly NAD-specific affinity (bio-affinity). The ribosyl-attached NAD(+) derivatives displayed negligible bio-affinity for any of the NAD-linked dehydrogenases tested. The most effective azo-linked derivative displayed strong bio-affinity for glycer-aldehyde 3-phosphate dehydrogenase, weaker bio-affinity for lactate dehydrogenase and none at all for malate dehydrogenase, although these three enzymes have very similar affinities for soluble NAD(+). Alcohol dehydrogenase and xanthine dehydrogenase were subject to such strong non-specific interactions with the hydrocarbon spacer-arm assembly that any specific affinity was completely eclipsed. 3. It is concluded that, in practice, the general effectiveness of a general ligand may be considerably distorted and attenuated by the nature of the immobilization linkage. However, this attenuation can result in an increase in specific effectiveness, allowing dehydrogenases to be separated from one another in a manner unlikely to be feasible if the general effectiveness of the ligand remained intact. 4. The bio-affinity of the various derivatives for lactate dehydrogenase is correlated with the known structure of the NAD(+)-binding site of this enzyme. Problems

  17. A homozygous mutation in a consanguineous family consolidates the role of ALDH1A3 in autosomal recessive microphthalmia.

    Science.gov (United States)

    Roos, L; Fang, M; Dali, C; Jensen, H; Christoffersen, N; Wu, B; Zhang, J; Xu, R; Harris, P; Xu, X; Grønskov, K; Tümer, Z

    2014-09-01

    Anomalies of eye development can lead to the rare eye malformations microphthalmia and anophthalmia (small or absent ocular globes), which are genetically very heterogeneous. Several genes have been associated with microphthalmia and anophthalmia, and exome sequencing has contributed to the identification of new genes. Very recently, homozygous variations within ALDH1A3 have been associated with autosomal recessive microphthalmia with or without cysts or coloboma, and with variable subphenotypes of developmental delay/autism spectrum disorder in eight families. In a consanguineous family where three of the five siblings were affected with microphthalmia/coloboma, we identified a novel homozygous missense mutation in ALDH1A3 using exome sequencing. Of the three affected siblings, one had intellectual disability and one had intellectual disability and autism, while the last one presented with normal development. This study contributes further to the description of the clinical spectrum associated with ALDH1A3 mutations, and illustrates the interfamilial clinical variation observed in individuals with ALDH1A3 mutations.

  18. Prognostic value of cancer stem cell markers CD133, ALDH1 and nuclearβ-catenin in colon cancer

    Institute of Scientific and Technical Information of China (English)

    Eman H.Abdelbary; Hayam E.Rashed; Eman I.Ismail; Mohamed Abdelgawad

    2014-01-01

    Colon cancer is one of the most common human malignancies. Cancer stem cells (CSCs), despite being only a smal subset of cancer cells, have the capability to self renew and sustain the tumor. They also have the ability to proliferate. Multiple CSCs associated markers have been identified in colon cancer including CD133, ALDH1 andβ catenin. The aim of the work was to study the prognostic value of CSCs markers (CD133, ALDH1 andβ catenin), as wel as their rela tionship to clinicopathological features of colon cancer. Methods:CD133, ALDH1 andβ catenin proteins expression was as sessed immunohistochemical y in a series of colon cancers and their prognostic significance was evaluated. Results:CD133 expression showed significant relationship to tumor stage and lymph node metastasis (P value 0.004&<0.001 respectively), and near significant relationship to liver metastasis (P value 0.092). ALDH1 was significantly associated with tumor grade, stage and nodal metastasis (P value 0.021, 0.001 and 0.026 respectively), but its relationship to liver metastasis was near sig nificant (P value 0.068). Nuclearβ catenin was significantly related to tumor grade, stage, nodal and liver metastasis (P value 0.001,<0.001,<0.001 and 0.008 respectively). Overal survival (OS) was associated inversely with CD133, ALDH1 positivity, and directly with nuclearβ catenin positivity (P value<0.001, 0.0001 and<0.001 respectively). Also recurrence free survival (RFS) was associated inversely with CD133, ALDH1 and directly with nuclearβ catenin positivity (P value 0.0001, 0.001 and<0.001 respectively). Conclusion:CD133, ALDH1 andβ catenin expressions of tumor cells have significant impact upon malignant progression of colon cancer and thus patient survival and tumor recurrence. Hence they can be used to predict outcome of colon cancer patients.

  19. Disulfiram Attenuates Drug-Primed Reinstatement of Cocaine Seeking via Inhibition of Dopamine β-Hydroxylase

    OpenAIRE

    Schroeder, Jason P; Cooper, Debra A.; Schank, Jesse R.; Lyle, Megan A.; Gaval-Cruz, Meriem; Ogbonmwan, Yvonne E.; Pozdeyev, Nikita; Freeman, Kimberly G; Iuvone, P. Michael; Edwards, Gaylen L.; Holmes, Philip V.; Weinshenker, David

    2010-01-01

    The antialcoholism medication disulfiram (Antabuse) inhibits aldehyde dehydrogenase (ALDH), which results in the accumulation of acetaldehyde upon ethanol ingestion and produces the aversive ‘Antabuse reaction' that deters alcohol consumption. Disulfiram has also been shown to deter cocaine use, even in the absence of an interaction with alcohol, indicating the existence of an ALDH-independent therapeutic mechanism. We hypothesized that disulfiram's inhibition of dopamine β-hydroxylase (DBH),...

  20. Two-Step biocatalytic conversion of an ester to an aldehyde in reverse micelles.

    Science.gov (United States)

    Yang, F; Russell, A J

    1994-02-01

    Lipases from Candida cyclindracea (L-1754) and wheat germ (L-3001) have been used to hydrolyze esters to their corresponding alcohols and acids in reverse micelles. Alcohol dehydrogenase from baker's yeast (YADH) was subsequently used to reduce the alcohol products to aldehydes. Cofactor recycling in the redox reaction was achieved using a sacrificial cosubstrate, as described previously. Four surfactants (sodium dioctylsulfosuccinate, Nonidet P-40 with Triton X-35, polyoxyethylene, 10-cetyl-ether, polyoxyethylene sorbitan trioleate) were employed to determine the effect of amphiphile on ester hydrolysis and redox reaction rates separately. The effect of type of organic solvent, W(0) [(water]/[surfactant)], and substrate concentration on separte enzyme activity were also investigated. A brief investigation of a single phase, two-step reaction catalyzed by the combination of lipase and YADH in reverse micelles is also reported. The activities of the enzymes are significantly different when used together instead of independently. (c) 1994 John Wiley & Sons, Inc.

  1. Biogenic aldehyde determination by reactive paper spray ionization mass spectrometry

    International Nuclear Information System (INIS)

    Highlights: • In-situ derivatization and simultaneous ionization used to detect aldehydes. • Biogenic aliphatic and aromatic aldehydes reacted with 4-aminophenol. • Derivatized products yield structurally characteristic fragment ions. • This measurement demonstrated using a miniaturized portable mass spectrometer. - Abstract: Ionization of aliphatic and aromatic aldehydes is improved by performing simultaneous chemical derivatization using 4-aminophenol to produce charged iminium ions during paper spray ionization. Accelerated reactions occur in the microdroplets generated during the paper spray ionization event for the tested aldehydes (formaldehyde, n-pentanaldehyde, n-nonanaldehyde, n-decanaldehyde, n-dodecanaldehyde, benzaldehyde, m-anisaldehyde, and p-hydroxybenzaldehyde). Tandem mass spectrometric analysis of the iminium ions using collision-induced dissociation demonstrated that straight chain aldehydes give a characteristic fragment at m/z 122 (shown to correspond to protonated 4-(methyleneamino)phenol), while the aromatic aldehyde iminium ions fragment to give a characteristic product ion at m/z 120. These features allow straightforward identification of linear and aromatic aldehydes. Quantitative analysis of n-nonaldehyde using a benchtop mass spectrometer demonstrated a linear response over 3 orders of magnitude from 2.5 ng to 5 μg of aldehyde loaded on the filter paper emitter. The limit of detection was determined to be 2.2 ng for this aldehyde. The method had a precision of 22%, relative standard deviation. The experiment was also implemented using a portable ion trap mass spectrometer

  2. Biogenic aldehyde determination by reactive paper spray ionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Bag, Soumabha; Hendricks, P.I. [Aston Labs, Department of Chemistry, Purdue University, West Lafayette, IN 47907 (United States); Reynolds, J.C. [Centre for Analytical Science, Loughborough University, Loughborough, Leicestershire (United Kingdom); Cooks, R.G., E-mail: cooks@purdue.edu [Aston Labs, Department of Chemistry, Purdue University, West Lafayette, IN 47907 (United States)

    2015-02-20

    Highlights: • In-situ derivatization and simultaneous ionization used to detect aldehydes. • Biogenic aliphatic and aromatic aldehydes reacted with 4-aminophenol. • Derivatized products yield structurally characteristic fragment ions. • This measurement demonstrated using a miniaturized portable mass spectrometer. - Abstract: Ionization of aliphatic and aromatic aldehydes is improved by performing simultaneous chemical derivatization using 4-aminophenol to produce charged iminium ions during paper spray ionization. Accelerated reactions occur in the microdroplets generated during the paper spray ionization event for the tested aldehydes (formaldehyde, n-pentanaldehyde, n-nonanaldehyde, n-decanaldehyde, n-dodecanaldehyde, benzaldehyde, m-anisaldehyde, and p-hydroxybenzaldehyde). Tandem mass spectrometric analysis of the iminium ions using collision-induced dissociation demonstrated that straight chain aldehydes give a characteristic fragment at m/z 122 (shown to correspond to protonated 4-(methyleneamino)phenol), while the aromatic aldehyde iminium ions fragment to give a characteristic product ion at m/z 120. These features allow straightforward identification of linear and aromatic aldehydes. Quantitative analysis of n-nonaldehyde using a benchtop mass spectrometer demonstrated a linear response over 3 orders of magnitude from 2.5 ng to 5 μg of aldehyde loaded on the filter paper emitter. The limit of detection was determined to be 2.2 ng for this aldehyde. The method had a precision of 22%, relative standard deviation. The experiment was also implemented using a portable ion trap mass spectrometer.

  3. Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

    DEFF Research Database (Denmark)

    Mills, Philippa B; Footitt, Emma J; Mills, Kevin A;

    2010-01-01

    Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of l-alpha-aminoadipic semialdehyde/L-Delta1-piperideine 6-carboxylate. However, whilst...... with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary L-alpha-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA......, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response...

  4. Purification and characterization of benzyl alcohol- and benzaldehyde- dehydrogenase from Pseudomonas putida CSV86.

    Science.gov (United States)

    Shrivastava, Rahul; Basu, Aditya; Phale, Prashant S

    2011-08-01

    Pseudomonas putida CSV86 utilizes benzyl alcohol via catechol and methylnaphthalenes through detoxification pathway via hydroxymethylnaphthalenes and naphthaldehydes. Based on metabolic studies, benzyl alcohol dehydrogenase (BADH) and benzaldehyde dehydrogenase (BZDH) were hypothesized to be involved in the detoxification pathway. BADH and BZDH were purified to apparent homogeneity and were (1) homodimers with subunit molecular mass of 38 and 57 kDa, respectively, (2) NAD(+) dependent, (3) broad substrate specific accepting mono- and di-aromatic alcohols and aldehydes but not aliphatic compounds, and (4) BADH contained iron and magnesium, while BZDH contained magnesium. BADH in the forward reaction converted alcohol to aldehyde and required NAD(+), while in the reverse reaction it reduced aldehyde to alcohol in NADH-dependent manner. BZDH showed low K (m) value for benzaldehyde as compared to BADH reverse reaction. Chemical cross-linking studies revealed that BADH and BZDH do not form multi-enzyme complex. Thus, the conversion of aromatic alcohol to acid is due to low K (m) and high catalytic efficiency of BZDH. Phylogenetic analysis revealed that BADH is a novel enzyme and diverged during the evolution to gain the ability to utilize mono- and di-aromatic compounds. The wide substrate specificity of these enzymes enables strain to detoxify methylnaphthalenes to naphthoic acids efficiently.

  5. DOXIL when combined with Withaferin A (WFA) targets ALDH1 positive cancer stem cells in ovarian cancer

    Science.gov (United States)

    Kakar, Sham S.; Worth, Christopher A.; Wang, Zhenglong; Carter, Kelsey; Ratajczak, Mariusz; Gunjal, Pranesh

    2016-01-01

    Ovarian cancer is a highly aggressive and deadly disease. Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly cisplatin or carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately, after few months of initial treatment, tumor relapse occurs due to platinum-resistance. DOXIL (liposomal preparation of doxorubicin) is a choice of drug for recurrent ovarian cancer. However, its response rate is very low and is accompanied by myocardial toxicity. Resistance to chemotherapy and recurrence of cancer is primarily attributed to the presence of cancer stem cells (CSCs), a small population of cells present in cancer. Effect of DOXIL and withaferin A (WFA), both alone and in combination, was investigated on cell proliferation of ovarian cancer cell line A2780 and tumor growth in SCID mice bearing i.p. ovarian tumors. ALDH1 cells were isolated from A2780 using cell sorter, and effect of DOXIL and WFA both alone and in combination on tumorigenic function of ALDH1 was studied using spheroids formation assays in vitro. Western blots were performed to examine the expression of ALDH1 and Notch 1 genes. In our studies, we showed, for the first time, that DOXIL when combined with withaferin A (WFA) elicits synergistic effect on inhibition of cell proliferation of ovarian cancer cells and inhibits the expression of ALDH1 protein, a marker for ALDH1 positive cancer stem cells (CSCs), and Notch1, a signaling pathway gene required for self-renewal of CSCs. Inhibition of expression of both ALDH1 and Notch1 genes by WFA was found to be dose dependent, whereas DOXIL (200 nM) was found to be ineffective. SCID mice, bearing i.p. ovarian tumors, were treated with a small dose of DOXIL (2 mg/kg) in combination with a sub-optimal dose of WFA (2 mg/kg) which resulted in a highly significant (60% to 70%) reduction in tumor growth, and complete inhibition of metastasis

  6. The oxidation of the aldehyde groups in dialdehyde starch

    NARCIS (Netherlands)

    Haaksman, I.K.; Besemer, A.C.; Jetten, J.M.; Timmermans, J.W.; Slaghek, T.M.

    2006-01-01

    This paper describes the difference in relative reactivity of the aldehyde groups present in dialdehyde starch towards different oxidising agents. The oxidation of dialdehyde starch with peracetic acid and sodium bromide leads to only partial oxidation to give mono-aldehyde-carboxy starch, while oxi

  7. Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders.

    Science.gov (United States)

    Moreno-Ramos, Oscar A; Olivares, Ana María; Haider, Neena B; de Autismo, Liga Colombiana; Lattig, María Claudia

    2015-01-01

    Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian-South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T>C (p.I505T)) and FOXN1 (RefSeq NM_003593: c.146C>T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in ~E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; ~P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding. PMID:26352270

  8. Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders.

    Science.gov (United States)

    Moreno-Ramos, Oscar A; Olivares, Ana María; Haider, Neena B; de Autismo, Liga Colombiana; Lattig, María Claudia

    2015-01-01

    Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian-South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T>C (p.I505T)) and FOXN1 (RefSeq NM_003593: c.146C>T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in ~E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; ~P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding.

  9. Bezafibrate induces FALDH in human fibroblasts; implications for Sjogren-Larsson syndrome

    NARCIS (Netherlands)

    J. Gloerich; L. Ijlst; R.J.A. Wanders; S. Ferdinandusse

    2006-01-01

    Sjogren-Larsson syndrome (SLS) is caused by a deficiency of fatty aldehyde dehydrogenase (FALDH), encoded by the ALDH3A2 gene. In animal studies, the expression of the murine ortholog of FALDH, has been shown to be under the control of peroxisome proliferator-activated receptor alpha (PPAR alpha). I

  10. Biochemical characterization of a bifunctional acetaldehyde-alcohol dehydrogenase purified from a facultative anaerobic bacterium Citrobacter sp. S-77.

    Science.gov (United States)

    Tsuji, Kohsei; Yoon, Ki-Seok; Ogo, Seiji

    2016-03-01

    Acetaldehyde-alcohol dehydrogenase (ADHE) is a bifunctional enzyme consisting of two domains of an N-terminal acetaldehyde dehydrogenase (ALDH) and a C-terminal alcohol dehydrogenase (ADH). The enzyme is known to be important in the cellular alcohol metabolism. However, the role of coenzyme A-acylating ADHE responsible for ethanol production from acetyl-CoA remains uncertain. Here, we present the purification and biochemical characterization of an ADHE from Citrobacter sp. S-77 (ADHE(S77)). Interestingly, the ADHE(S77) was unable to be solubilized from membrane with detergents either 1% Triton X-100 or 1% Sulfobetaine 3-12. However, the enzyme was easily dissociated from membrane by high-salt buffers containing either 1.0 M NaCl or (NH(4))(2)SO(4) without detergents. The molecular weight of a native protein was estimated as approximately 400 kDa, consisting of four identical subunits of 96.3 kDa. Based on the specific activity and kinetic analysis, the ADHES77 tended to have catalytic reaction towards acetaldehyde elimination rather than acetaldehyde formation. Our experimental observation suggests that the ADHES77 may play a pivotal role in modulating intracellular acetaldehyde concentration.

  11. Molecular Structure and Reactivity in the Pyrolysis of Aldehydes

    Science.gov (United States)

    Sias, Eric; Cole, Sarah; Sowards, John; Warner, Brian; Wright, Emily; McCunn, Laura R.

    2016-06-01

    The effect of alkyl chain structure on pyrolysis mechanisms has been investigated in a series of aldehydes. Isovaleraldehyde, CH_3CH(CH_3)CH_2CHO, and pivaldehyde, (CH_3)_3CCHO, were subject to thermal decomposition in a resistively heated SiC tubular reactor at 800-1200 °C. Matrix-isolation FTIR spectroscopy was used to identify pyrolysis products. Carbon monoxide and isobutene were major products from each of the aldehydes, which is consistent with what is known from previous studies of unbranched alkyl-chain aldehydes. Other products observed include vinyl alcohol, propene, acetylene, and ethylene, revealing complexities to be considered in the pyrolysis of large, branched-chain aldehydes.

  12. Glucose-6-Phosphate Dehydrogenase Deficiency Overview

    Science.gov (United States)

    ... Drugs GARD Information Navigator FAQs About Rare Diseases Glucose-6-phosphate dehydrogenase deficiency Title Other Names: G6PD ... G6PD deficiency Categories: Newborn Screening Summary Summary Listen Glucose 6 phosphate dehydrogenase (G6PD) deficiency is a hereditary ...

  13. Sorbitol dehydrogenase is a zinc enzyme.

    OpenAIRE

    Jeffery, J; Chesters, J; C. Mills; P.J. Sadler; Jörnvall, H

    1984-01-01

    Evidence is given that tetrameric sorbitol dehydrogenase from sheep liver contains one zinc atom per subunit, most probably located at the active site, and no other specifically bound zinc or iron atom. In alcohol dehydrogenases that are structurally related to sorbitol dehydrogenase, more than one zinc atom per subunit can complicate investigations of zinc atom function. Therefore, sorbitol dehydrogenase will be particularly valuable for defining the precise roles of zinc in alcohol and poly...

  14. Specific biotinylation of IMP dehydrogenase

    OpenAIRE

    Hoefler, B. Christopher; Gollapalli, Deviprasad R.; Hedstrom, Lizbeth

    2011-01-01

    IMP dehydrogenase (IMPDH) catalyzes a critical step in guanine nucleotide biosynthesis. IMPDH also has biological roles that are distinct from its enzymatic function. We report a biotin-linked reagent that selectively labels IMPDH and is released by dithiothreitol. This reagent will be invaluable in elucidating the moonlighting functions of IMPDH.

  15. Amine-functionalized porous silicas as adsorbents for aldehyde abatement.

    Science.gov (United States)

    Nomura, Akihiro; Jones, Christopher W

    2013-06-26

    A series of aminopropyl-functionalized silicas containing of primary, secondary, or tertiary amines is fabricated via silane-grafting on mesoporous SBA-15 silica and the utility of each material in the adsorption of volatile aldehydes from air is systematically assessed. A particular emphasis is placed on low-molecular-weight aldehydes such as formaldehyde and acetaldehyde, which are highly problematic volatile organic compound (VOC) pollutants. The adsorption tests demonstrate that the aminosilica materials with primary amines most effectively adsorbed formaldehyde with an adsorption capacity of 1.4 mmolHCHO g(-1), whereas the aminosilica containing secondary amines showed lower adsorption capacity (0.80 mmolHCHO g(-1)) and the aminosilica containing tertiary amines adsorbed a negligible amount of formaldehyde. The primary amine containing silica also successfully abated higher aldehyde VOC pollutants, including acetaldehyde, hexanal, and benzaldehyde, by effectively adsorbing them. The adsorption mechanism is investigated by (13)C CP MAS solid-state NMR and FT-Raman spectroscopy, and it is demonstrated that the aldehydes are chemically attached to the surface of aminosilica in the form of imines and hemiaminals. The high aldehyde adsorption capacities of the primary aminosilicas in this study demonstrate the utility of amine-functionalized silica materials for reduction of gaseous aldehydes.

  16. Aldehyde oxidase activity in fresh human skin.

    Science.gov (United States)

    Manevski, Nenad; Balavenkatraman, Kamal Kumar; Bertschi, Barbara; Swart, Piet; Walles, Markus; Camenisch, Gian; Schiller, Hilmar; Kretz, Olivier; Ling, Barbara; Wettstein, Reto; Schaefer, Dirk J; Pognan, Francois; Wolf, Armin; Litherland, Karine

    2014-12-01

    Human aldehyde oxidase (AO) is a molybdoflavoenzyme that commonly oxidizes azaheterocycles in therapeutic drugs. Although high metabolic clearance by AO resulted in several drug failures, existing in vitro-in vivo correlations are often poor and the extrahepatic role of AO practically unknown. This study investigated enzymatic activity of AO in fresh human skin, the largest organ of the body, frequently exposed to therapeutic drugs and xenobiotics. Fresh, full-thickness human skin was obtained from 13 individual donors and assayed with two specific AO substrates: carbazeran and zoniporide. Human skin explants from all donors metabolized carbazeran to 4-hydroxycarbazeran and zoniporide to 2-oxo-zoniporide. Average rates of carbazeran and zoniporide hydroxylations were 1.301 and 0.164 pmol⋅mg skin(-1)⋅h(-1), resulting in 13 and 2% substrate turnover, respectively, after 24 hours of incubation with 10 μM substrate. Hydroxylation activities for the two substrates were significantly correlated (r(2) = 0.769), with interindividual variability ranging from 3-fold (zoniporide) to 6-fold (carbazeran). Inclusion of hydralazine, an irreversible inhibitor of AO, resulted in concentration-dependent decrease of hydroxylation activities, exceeding 90% inhibition of carbazeran 4-hydroxylation at 100 μM inhibitor. Reaction rates were linear up to 4 hours and well described by Michaelis-Menten enzyme kinetics. Comparison of carbazeran and zoniporide hydroxylation with rates of triclosan glucuronidation and sulfation and p-toluidine N-acetylation showed that cutaneous AO activity is comparable to tested phase II metabolic reactions, indicating a significant role of AO in cutaneous drug metabolism. To our best knowledge, this is the first report of AO enzymatic activity in human skin. PMID:25249692

  17. Sorption Behavior of an Aliphatic Series of Aldehydes in the Presence of Poly(ethylene terephthalate) Blends Containing Aldehyde Scavenging Agents

    OpenAIRE

    Suloff, Eric Charles

    2002-01-01

    The quality of many beverages and food products is compromised by the presence of low molecular weight aldehydes. Aldehydes are commonly formed during storage by the oxidation of lipids or are introduced as migrants from polymeric packaging material. The objective of this project was to evaluate the effectiveness of three aldehyde scavenging agents, blended into poly(ethylene terephthalate) (PET) films, in removing an aliphatic series of aldehydes from an acidified aqueous model solution (p...

  18. [The effect of subchronic inhalations of nitric oxide on metabolic processes in blood of experimental animals].

    Science.gov (United States)

    Soloveva, A G; Peretyagin, S P

    2016-01-01

    Metabolic processes were investigated in plasma and erythrocytes of Wistar rats exposed to daily 10-min sessions of NO inhalation for 30 days. These included determination of glucose and lactate, catalase activity, and activities of aldehyde dehydrogenase (ALDH), lactate dehydrogenase (LDH), and catalase. NO inhalation in a concentration of 20 ppm, 50 ppm and 100 ppm caused an increase in glucose and lactate. Inhalation of 100 ppm NO also increased catalase activity. Inhalation of all NO concentrations resulted in a decrease of ALDH activity, while the decrease in LDH activity was observed at NO concentrations of 50-100 ppm. PMID:27143382

  19. Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Lee, Jae-Ha [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Seo-Yoen; Kim, Jeong-Yul [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Cho, Eun-Wie [Epigenomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of)

    2014-11-21

    Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation.

  20. Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

    International Nuclear Information System (INIS)

    Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation

  1. Novel NAD+-Farnesal Dehydrogenase from Polygonum minus Leaves. Purification and Characterization of Enzyme in Juvenile Hormone III Biosynthetic Pathway in Plant

    Science.gov (United States)

    Mohamed-Hussein, Zeti-Azura; Ng, Chyan Leong

    2016-01-01

    Juvenile Hormone III is of great concern due to negative effects on major developmental and reproductive maturation in insect pests. Thus, the elucidation of enzymes involved JH III biosynthetic pathway has become increasing important in recent years. One of the enzymes in the JH III biosynthetic pathway that remains to be isolated and characterized is farnesal dehydrogenase, an enzyme responsible to catalyze the oxidation of farnesal into farnesoic acid. A novel NAD+-farnesal dehydrogenase of Polygonum minus was purified (315-fold) to apparent homogeneity in five chromatographic steps. The purification procedures included Gigacap S-Toyopearl 650M, Gigacap Q-Toyopearl 650M, and AF-Blue Toyopearl 650ML, followed by TSK Gel G3000SW chromatographies. The enzyme, with isoelectric point of 6.6 is a monomeric enzyme with a molecular mass of 70 kDa. The enzyme was relatively active at 40°C, but was rapidly inactivated above 45°C. The optimal temperature and pH of the enzyme were found to be 35°C and 9.5, respectively. The enzyme activity was inhibited by sulfhydryl agent, chelating agent, and metal ion. The enzyme was highly specific for farnesal and NAD+. Other terpene aldehydes such as trans- cinnamaldehyde, citral and α- methyl cinnamaldehyde were also oxidized but in lower activity. The Km values for farnesal, citral, trans- cinnamaldehyde, α- methyl cinnamaldehyde and NAD+ were 0.13, 0.69, 0.86, 1.28 and 0.31 mM, respectively. The putative P. minus farnesal dehydrogenase that’s highly specific towards farnesal but not to aliphatic aldehydes substrates suggested that the enzyme is significantly different from other aldehyde dehydrogenases that have been reported. The MALDI-TOF/TOF-MS/MS spectrometry further identified two peptides that share similarity to those of previously reported aldehyde dehydrogenases. In conclusion, the P. minus farnesal dehydrogenase may represent a novel plant farnesal dehydrogenase that exhibits distinctive substrate specificity

  2. Regulation of Ethanol-Related Behavior and Ethanol Metabolism by the Corazonin Neurons and Corazonin Receptor in Drosophila melanogaster

    OpenAIRE

    Kai Sha; Seung-Hoon Choi; Jeongdae Im; Gyunghee G Lee; Frank Loeffler; Park, Jae H.

    2014-01-01

    Impaired ethanol metabolism can lead to various alcohol-related health problems. Key enzymes in ethanol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH); however, neuroendocrine pathways that regulate the activities of these enzymes are largely unexplored. Here we identified a neuroendocrine system involving Corazonin (Crz) neuropeptide and its receptor (CrzR) as important physiological regulators of ethanol metabolism in Drosophila. Crz-cell deficient (Crz-CD) fli...

  3. Tunable Ether Production via Coupling of Aldehydes or Aldehyde/Alcohol over Hydrogen-Modified Gold Catalysts at Low Temperatures.

    Science.gov (United States)

    Pan, Ming; Brush, Adrian J; Dong, Guangbin; Mullins, C Buddie

    2012-09-01

    Ethers are an important group of organic compounds that are primarily prepared via homogeneous catalysis, which can lead to operational and environmental issues. Here we demonstrate the production of ethers via heterogeneous catalysis over H adatom-covered gold at temperatures lower than 250 K. Symmetrical ethers can be formed via a self-coupling reaction of corresponding aldehydes; for example, homocoupling of acetaldehyde and propionaldehyde yields diethyl ether and di-n-propyl ether, respectively. In addition, coupling reactions between alcohols and aldehydes, with different carbon chain lengths, are observed via the production of the corresponding unsymmetrical ethers. A reaction mechanism is proposed, suggesting that an alcohol-like intermediate via partial hydrogenation of aldehydes on the surface plays a key role in these reactions. These surface chemical reactions suggest possible heterogeneous routes to low-temperature production of ethers. PMID:26292142

  4. Acetaldehyde dehydrogenase 2 activation inhibits myocardial ischemia-reperfusion injury in senescent rats%激活乙醛脱氢酶2抑制老年大鼠心肌缺血再灌注损伤

    Institute of Scientific and Technical Information of China (English)

    邢媛; 殷玥; 石曌玲; 李晨; 王博文; 王衍帅; 高峰; 马恒

    2013-01-01

    Objective Aging heart shows significantly reduced tolerance to myocardial ischemia/reperfusion (I/R) injury, so senescent heart is prone to be damaged by the injury. This study was designed to investigate the protective effect of acetaldehyde dehydrogenase 2 (ALDH2) agonist Alda-1 in aging rats after myocardial I/R injury. Methods A total of 40 aging male Sprague Dawley (SD) rats (at an age of 20 to 22 months) were randomized into I/R group (I/R) and Alda-1 group (I/R + Alda). Another 40 adult rats at an age of 3 to 4 months served as adult control. Rat acute myocardial I/R model was established by ligation of left anterior descending artery for 30min followed by reperfusion for 4h. Alda-l(16mg/kg) and normal saline at the same volume were intravenously infused at a flow rate of 2ml/(kg · h) into the left ventricle of corresponding rats in 5min before reperfusion. The left ventricular pressure was monitored at the same time. At the end of 4 hours reperfusion, ALDH2 activity, reactive oxygen species (ROS) production, and protein carbonylation in the myocardial tissue were measured. Serum level of lactate dehydrogenase (LDH) was tested. Results A significant decrease in ALDH2 activity was observed in the aging hearts, but this effect was blocked by Alda-1. Compared with the adult hearts, myocardial I/R injury was significantly aggravated in aging hearts, which were evidenced by reduced ± LVdP/dtmax and increased serum level of LDH (P < 0.05). ALDH2 activator infusion during reperfusion effectively suppressed the above mentioned ischemic injury in the aging hearts (P < 0.05). Furthermore, protein carbonylation and ROS production in the myocardium were increased in the aging hearts compared with the adult hearts (P < 0.05), which was attenuated by Alda-1 treatment. Conclusion Activating myocardial ALDH2 significantly improves the resistance ability to myocardial I/R injury in aging heart. ALDH2-induced cardiac protection may be through suppressing myocardial I

  5. Enzymic and structural studies on Drosophila alcohol dehydrogenase and other short-chain dehydrogenases/reductases

    NARCIS (Netherlands)

    Smilda, T; Kamminga, AH; Reinders, P; Baron, W; Vlieg, JETV; Beintema, JJ

    2001-01-01

    Enzymic and structural studies on Drosophila alcohol dehydrogenases and other short-chain dehydrogenases/reductases (SDRs) are presented. Like alcohol dehydrogenases from other Drosophila species, the enzyme from D, simulans is more active on secondary than on primary alcohols, although ethanol is i

  6. Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis

    Science.gov (United States)

    Macgregor, Stuart; Lind, Penelope A.; Bucholz, Kathleen K.; Hansell, Narelle K.; Madden, Pamela A.F.; Richter, Melinda M.; Montgomery, Grant W.; Martin, Nicholas G.; Heath, Andrew C.; Whitfield, John B.

    2009-01-01

    Alcohol dependence (AD) is a complex disorder with environmental and genetic origins. The role of two genetic variants in ALDH2 and ADH1B in AD risk has been extensively investigated. This study tested for associations between nine polymorphisms in ALDH2 and 41 in the seven ADH genes, and alcohol-related flushing, alcohol use and dependence symptom scores in 4597 Australian twins. The vast majority (4296) had consumed alcohol in the previous year, with 547 meeting DSM-IIIR criteria for AD. There were study-wide significant associations (P < 2.3 × 10−4) between ADH1B-Arg48His (rs1229984) and flushing and consumption, but only nominally significant associations (P < 0.01) with dependence. Individuals carrying the rs1229984 G-allele (48Arg) reported a lower prevalence of flushing after alcohol (P = 8.2 × 10−7), consumed alcohol on more occasions (P = 2.7 × 10−6), had a higher maximum number of alcoholic drinks in a single day (P = 2.7 × 10−6) and a higher overall alcohol consumption (P = 8.9 × 10−8) in the previous year than those with the less common A-allele (48His). After controlling for rs1229984, an independent association was observed between rs1042026 (ADH1B) and alcohol intake (P = 4.7 × 10−5) and suggestive associations (P < 0.001) between alcohol consumption phenotypes and rs1693482 (ADH1C), rs1230165 (ADH5) and rs3762894 (ADH4). ALDH2 variation was not associated with flushing or alcohol consumption, but was weakly associated with AD measures. These results bridge the gap between DNA sequence variation and alcohol-related behavior, confirming that the ADH1B-Arg48His polymorphism affects both alcohol-related flushing in Europeans and alcohol intake. The absence of study-wide significant effects on AD results from the low P-value required when testing multiple single nucleotide polymorphisms and phenotypes. PMID:18996923

  7. Acetic acid assisted cobalt methanesulfonate catalysed chemoselective diacetylation of aldehydes

    Institute of Scientific and Technical Information of China (English)

    Min Wang; Zhi Guo Song; Hong Gong; Heng Jiang

    2008-01-01

    Cobalt methanesulfonate in combination with acetic acid catalysed the chemoselective diacetylation of aldehyde with acetic anhydride at room temperature under solvent free conditions. After reaction, cobalt methanesulfonate can be easily recovered and mused many times. The reaction was mild and efficient with good to high yields.

  8. Reaction of benzoxasilocines with aromatic aldehydes: Synthesis of homopterocarpans

    Directory of Open Access Journals (Sweden)

    Rodríguez-García Ignacio

    2007-02-01

    Full Text Available Abstract Condensation of 2H-benzo[g][1,2]oxasilocines with aromatic aldehydes in the presence of boron trifluoride affords mixtures of cis/trans 2-phenyl-3-vinylchromans with moderate yields. These can be transformed into homopterocarpans, a synthetic group of substances homologous to the natural isoflavonoid pterocarpans.

  9. INTERACTION OF ALDEHYDES DERIVED FROM LIPID PEROXIDATION AND MEMBRANE PROTEINS.

    Directory of Open Access Journals (Sweden)

    Stefania ePizzimenti

    2013-09-01

    Full Text Available A great variety of compounds are formed during lipid peroxidation of polyunsaturated fatty acids of membrane phospholipids. Among them, bioactive aldehydes, such as 4-hydroxyalkenals, malondialdehyde (MDA and acrolein, have received particular attention since they have been considered as toxic messengers that can propagate and amplify oxidative injury. In the 4-hydroxyalkenal class, 4-hydroxy-2-nonenal (HNE is the most intensively studied aldehyde, in relation not only to its toxic function, but also to its physiological role. Indeed, HNE can be found at low concentrations in human tissues and plasma and participates in the control of biological processes, such as signal transduction, cell proliferation and differentiation. Moreover, at low doses, HNE exerts an anti-cancer effect, by inhibiting cell proliferation, angiogenesis, cell adhesion and by inducing differentiation and/or apoptosis in various tumor cell lines. It is very likely that a substantial fraction of the effects observed in cellular responses, induced by HNE and related aldehydes, be mediated by their interaction with proteins, resulting in the formation of covalent adducts or in the modulation of their expression and/or activity. In this review we focus on membrane proteins affected by lipid peroxidation-derived aldehydes, under physiological and pathological conditions.

  10. Tandem Aldol Condensation – Platinacycle-Catalyzed Addition Reactions of Aldehydes, Methyl Ketones and Arylboronic Acids

    OpenAIRE

    Liao, Yuan-Xi; Hu, Qiao-Sheng

    2012-01-01

    Tandem aldol condensation of aldehydes with methyl ketones followed by anionic four-electron donor-based (Type I) platinacycle-catalyzed addition reactions of arylboronic acids to form β-arylated ketones is described. Good to excellent yields of β-arylated ketones were obtained for the tandem reactions of aromatic/aliphatic aldehydes, methyl ketones and arylboronic acids, and moderate yields were observed for the tandem reaction with α, β-unsaturated aldehydes as the aldehyde source.

  11. Unsaturated aldehydes as alkene equivalents in the Diels-Alder reaction

    DEFF Research Database (Denmark)

    Taarning, Esben; Madsen, Robert

    2008-01-01

    A one-pot procedure is described for using alpha,beta-unsaturated aldehydes as olefin equivalents in the Diels-Alder reaction. The method combines the normal electron demand cycloaddition with aldehyde dienophiles and the rhodium-catalyzed decarbonylation of aldehydes to afford cyclohexenes with ...

  12. Immunohistochemical analysis of aldehyde dehydrogenase isoforms and their association with estrogen-receptor status and disease progression in breast cancer

    OpenAIRE

    Opdenaker LM; Arnold KM; Pohlig RT; Padmanabhan JS; Flynn DC; Sims-Mourtada J

    2014-01-01

    Lynn M Opdenaker,1,2 Kimberly M Arnold,1,3 Ryan T Pohlig,3,4 Jayasree S Padmanabhan,1 Daniel C Flynn,1,3 Jennifer Sims-Mourtada1–3 1Center for Translational Cancer Research, Helen F Graham Cancer Center, Christiana Care Health Services, Inc., Newark, Delaware, USA; 2Department of Biological Sciences, 3Department of Medical Laboratory Sciences, 4Biostatistics Core Facility, University of Delaware, Newark, Delaware, USA Abstract: In many types of tumors, especially breast tumors, ald...

  13. Human cord blood progenitors with high aldehyde dehydrogenase activity improve vascular density in a model of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Creer Michael H

    2010-03-01

    Full Text Available Abstract Human stem cells from adult sources have been shown to contribute to the regeneration of muscle, liver, heart, and vasculature. The mechanisms by which this is accomplished are, however, still not well understood. We tested the engraftment and regenerative potential of human umbilical cord blood-derived ALDHhiLin-, and ALDHloLin- cells following transplantation to NOD/SCID or NOD/SCID β2m null mice with experimentally induced acute myocardial infarction. We used combined nanoparticle labeling and whole organ fluorescent imaging to detect human cells in multiple organs 48 hours post transplantation. Engraftment and regenerative effects of cell treatment were assessed four weeks post transplantation. We found that ALDHhiLin- stem cells specifically located to the site of injury 48 hours post transplantation and engrafted the infarcted heart at higher frequencies than ALDHloLin- committed progenitor cells four weeks post transplantation. We found no donor derived cardiomyocytes and few endothelial cells of donor origin. Cell treatment was not associated with any detectable functional improvement at the four week endpoint. There was, however, a significant increase in vascular density in the central infarct zone of ALDHhiLin- cell-treated mice, as compared to PBS and ALDHloLin- cell-treated mice. Conclusions Our data indicate that adult human stem cells do not become a significant part of the regenerating tissue, but rapidly home to and persist only temporarily at the site of hypoxic injury to exert trophic effects on tissue repair thereby enhancing vascular recovery.

  14. Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects on human health.

    Science.gov (United States)

    O'Brien, Peter J; Siraki, Arno G; Shangari, Nandita

    2005-08-01

    Aldehydes are organic compounds that are widespread in nature. They can be formed endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate autoxidation, amine oxidases, cytochrome P-450s, or myeloperoxidase-catalyzed metabolic activation. This review compares the reactivity of many aldehydes towards biomolecules particularly macromolecules. Furthermore, it includes not only aldehydes of environmental or occupational concerns but also dietary aldehydes and aldehydes formed endogenously by intermediary metabolism. Drugs that are aldehydes or form reactive aldehyde metabolites that cause side-effect toxicity are also included. The effects of these aldehydes on biological function, their contribution to human diseases, and the role of nucleic acid and protein carbonylation/oxidation in mutagenicity and cytotoxicity mechanisms, respectively, as well as carbonyl signal transduction and gene expression, are reviewed. Aldehyde metabolic activation and detoxication by metabolizing enzymes are also reviewed, as well as the toxicological and anticancer therapeutic effects of metabolizing enzyme inhibitors. The human health risks from clinical and animal research studies are reviewed, including aldehydes as haptens in allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic drug toxicity; the potential carcinogenic risks of the carbonyl body burden; and the toxic effects of aldehydes in liver disease, embryo toxicity/teratogenicity, diabetes/hypertension, sclerosing peritonitis, cerebral ischemia/neurodegenerative diseases, and other aging-associated diseases.

  15. Genes that modulate susceptibility for alcohol dependence

    OpenAIRE

    Caio Cesar Silva de Cerqueira; Domingos Lázaro Souza Rios

    2008-01-01

    The pathways for the metabolism of the alcohol are complex and modulated by some genes that promote response to this substance. The genes that codify the enzyme alcohol dehydrogenase (os genes ADH1B or ADH2) act in the conversion of ethanol in acetaldehyde; the enzyme aldehyde dehydrogenase (ALDH2) that converts the aldehyde into ascetic acid, and the gene that codifies the enzyme cytochrome P450, isoform 2E1 (CYP2E1), that acts generating free radicals of great importance in the induced hepa...

  16. An efficient and versatile synthesis of aromatic nitriles from aldehydes

    Institute of Scientific and Technical Information of China (English)

    Maryam Hajjami; Arash Ghorbani-Choghamarani; Mohammad Ali Zolfigol; Fatemeh Gholamian

    2012-01-01

    A simple and direct method has been developed for synthesis of nitriles based on one-pot reaction of aromatic aldehydes with three different kind of reagents:CeCl3·7H2O/KI/H2O2,CeCl3·7H2O/KI/UHP and (NH4)2Ce(NO3)6/KI/H2O2 in aqueous ammonia.

  17. γ-Unsaturated aldehydes as potential Lilial replacers.

    Science.gov (United States)

    Schroeder, Martin; Mathys, Marion; Ehrensperger, Nadja; Büchel, Michelle

    2014-10-01

    A series of Claisen rearrangements was undertaken in order to find a replacement for Lilial (=3-(4-(tert-butyl)phenyl)-2-methylpropanal), a high-tonnage perfumery ingredient with a lily-of-the-valley odour, which is a CMR2 material [1]. 5,7,7-Trimethyl-4-methyleneoctanal (10), the synthesis of which is described, became the main lead. It possesses an odour which is very close to that of Lilial but lacks its substantivity. Aldehydes with higher molecular weights than that of 10 were, therefore, synthesised in order to boost substantivity and to understand the structural requirements for a 'Lilial' odour. The aldehydes were obtained via Claisen rearrangements of 'exo-methylidene' vinyl ethers, allenyl vinyl ethers, or allenyl allyl ethers. Alternatively, coupling of terminal alkynes with allyl alcohols led to the desired aldehydes. Derivatives of 10 and their sila analogues were also synthesised. The olfactory properties of all synthesised molecules were evaluated for possible structure-odour relationships (SOR). PMID:25329790

  18. 21 CFR 862.1670 - Sorbitol dehydrogenase test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Sorbitol dehydrogenase test system. 862.1670... Systems § 862.1670 Sorbitol dehydrogenase test system. (a) Identification. A sorbitol dehydrogenase test system is a device intended to measure the activity of the enzyme sorbitol dehydrogenase in...

  19. Studies on 2-oxoacid dehydrogenase multienzyme complexes of Azotobacter vinelandii

    NARCIS (Netherlands)

    Bosma, H.J.

    1984-01-01

    In this thesis, some studies on the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase multienzyme complexes of Azotobacter vinelandii are described; the emphasis strongly lies on the pyruvate dehydrogenase complex.A survey of the literature on 2-oxoacid dehydrogenase complexes is given in chap

  20. In vitro assessment of human airway toxicity from major aldehydes in automotive emissions

    Energy Technology Data Exchange (ETDEWEB)

    Grafstroem, R.C. [Karolinska Inst., Stockholm (Sweden). Inst. of Environmental Medicine

    1997-09-01

    Automotive exhausts can significantly contribute to the levels of reactive aldehydes, including formaldehyde, acetaldehyde and acrolein, in urban air. The use of alcohols as an alternative fuel for gasoline or diesel may further increase these emissions. Since it is unclear if aldehyde inhalation may induce pathological states, including cancer, in human airways, the toxic properties of the above-mentioned aldehydes were studied in cultured target cell types. Each aldehyde modified vital cellular functions in a dose-dependent manner, and invariably inhibited growth and induced abnormal terminal differentiation. Decreases of cellular thiols and increases of intracellular Ca{sup 2+} were observed, and moreover, variable types and amounts of short-lived or persistent genetic damage were induced. The concentrations required for specified levels of a particular type of injury varied up to 10000-fold among the aldehydes. Overall, distinctive patterns of cytopathological activity were observed, which differed both qualitatively and quantitatively among the aldehydes. Finally, aldehydes inhibited DNA repair processes and increased cytotoxicity and mutagenesis in synergy with other known toxicants, indicating that aldehydes may also enhance damage by other constituents in automotive exhausts. In summary, the aldehydes, notably {sup m}u{sup M}-mM formaldehyde, caused pathological effects and induced mechanisms that relate to acute toxicity and cancer development in airway epithelial cells. Since `no-effect` levels may not exist for carcinogenic agents, the overall results support a need for elimination of aldehydes in automotive exhausts. 41 refs

  1. Telomere shortening in the esophagus of Japanese alcoholics: relationships with chromoendoscopic findings, ALDH2 and ADH1B genotypes and smoking history.

    Directory of Open Access Journals (Sweden)

    Junko Aida

    Full Text Available Chromoendoscopy with Lugol iodine staining provides important information on the development of squamous cell carcinoma (SCC. In particular, distinct iodine-unstained lesions (DIULs larger than 10 mm show a high prevalence in high-grade intraepithelial neoplasia. It has also been reported that inactive ALDH2*1/*2 and less-active ADH1B*1/*1, and smoking, are risk factors for esophageal SCC. We previously examined telomere shortening in the esophageal epithelium of alcoholics, and suggested a high prevalence of chromosomal instability in such individuals. In the present study, we attempted to analyze telomere lengths in 52 DIULs with reference to both their size and multiplicity, ALDH2 and ADH1B genotypes, and smoking history. Patients with DIULs <10 mm (n = 42 had significantly longer telomeres than those with DIULs ≥10 mm (n = 10, p = 0.008. No significant differences in telomere length were recognized between the ALDH2 and ADH1B genotypes (ALDH2 active/inactive = 35/17, ADH1B active/inactive = 32/20; p = 0.563, 0.784, respectively or among four groups of patients divided according to smoking history (never-, ex-, light, and heavy smokers = 3, 6, 21, and 22 patients, respectively; p = 0.956. Patients without multiple DIULs (n = 17 had significantly longer telomeres than patients with multiple DIULs (n = 35, p = 0.040. It is suggested that alcoholism reduces telomere length in the esophagus, irrespective of genotype or smoking habit. Telomere shortening may not generate cancer directly, but may create conditions under which SCC can develop more easily, depending on subsequent exposure to carcinogens.

  2. Co-transforming bar and CsALDH genes enhanced resistance to herbicide and drought and salt stress in transgenic alfalfa (Medicago sativa L.

    Directory of Open Access Journals (Sweden)

    Zhen eDuan

    2015-12-01

    Full Text Available Drought and high salinity are two major abiotic factors that restrict the productivity of alfalfa. By application of the Agrobacterium-mediated transformation method, an oxidative responsive gene, CsALDH12A1, from the desert grass Cleistogenes songorica together with the bar gene associated with herbicide resistance, were co-transformed into alfalfa (Medicago sativa L.. From the all 90 transformants, 16 were positive as screened by spraying 1 mL L-1 10% Basta solution and molecularly diagnosis using PCR. Real-time PCR analysis indicated that drought and salt stress induced high CsALDH expression in the leaves of the transgenic plants. The CsALDH expression levels under drought (15 d and salt stress (200 mM NaCl were 6.11 and 6.87 times higher than in the control plants, respectively. In comparison to the WT plants, no abnormal phenotypes were observed among the transgenic plants, which showed significant enhancement of tolerance to 15 d of drought and 10 d of salinity treatment. Evaluation of the physiological and biochemical indices during drought and salt stress of the transgenic plants revealed relatively lower Na+ content and higher K+ content in the leaves relative to the WT plants, a reduction of toxic on effects and maintenance of osmotic adjustment. In addition, the transgenic plants could maintain a higher relative water content (RWC level, higher shoot biomass, fewer changes in the photosystem, decreased membrane injury, and a lower level of osmotic stress. These results indicate that the co-expression of the introduced bar and CsALDH genes enhanced the herbicide, drought and salt tolerance of alfalfa and therefore can potentially be used as a novel genetic resource for the future breeding programs to develop new cultivars.

  3. Transcriptional Regulation of Pyruvate Dehydrogenase Kinase

    OpenAIRE

    Ji Yun Jeong; Nam Ho Jeoung; Keun-Gyu Park; In-Kyu Lee

    2012-01-01

    The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK) isoenzymes. Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally re...

  4. Screening of aspartate dehydrogenase of bacteria

    OpenAIRE

    Fukuda, Shoko; Okamura, Tokumitsu; Yasumasa, Izumi; Takeno, Tomomi; Ohsugi, Masahiro

    2001-01-01

    Fifty-two strains of bacteria cultured under aerobic conditions and 12 strains of bacteria cultured under anaerobic conditions demonstrated high activity staining of aspartate dehydrogenase with NAD^+. Four strains of bacteria cultured under aerobic conditions and 7 strains of bacteria cultured under anaerobic conditions demonstrated high activity staining of aspartate dehydrogenase with NADP^+. Seven strains of bacteria cultured under aerobic conditions and 4 strains of bacteria cultured und...

  5. Phosphorylation site on yeast pyruvate dehydrogenase complex

    International Nuclear Information System (INIS)

    The pyruvate dehydrogenase complex was purified to homogeneity from baker's yeast (Saccharomyces cerevisiae). Yeast cells were disrupted in a Manton-Gaulin laboratory homogenizer. The pyruvate dehydrogenase complex was purified by fractionation with polyethylene glycol, isoelectric precipitation, ultracentrifugation and chromatography on hydroxylapatite. Final purification of the yeast pyruvate dehydrogenase complex was achieved by cation-exchange high pressure liquid chromatography (HPLC). No endogenous pyruvate dehydrogenase kinase activity was detected during the purification. However, the yeast pyruvate dehydrogenase complex was phosphorylated and inactivated with purified pyruvate dehydrogenase kinase from bovine kidney. Tryptic digestion of the 32P-labeled complex yielded a single phosphopeptide which was purified to homogeniety. The tryptic digest was subjected to chromatography on a C-18 reverse phase HPLC column with a linear gradient of acetonitrile. Radioactive fractions were pooled, concentrated, and subjected to anion-exchange HPLC. The column was developed with a linear gradient of ammonium acetate. Final purification of the phosphopeptide was achieved by chromatography on a C-18 reverse phase HPLC column developed with a linear gradient of acetonitrile. The amino acid sequence of the homogeneous peptide was determined by manual modified Edman degradation

  6. ALDH1A3 loss of function causes bilateral anophthalmia/microphthalmia and hypoplasia of the optic nerve and optic chiasm.

    Science.gov (United States)

    Yahyavi, Mani; Abouzeid, Hana; Gawdat, Ghada; de Preux, Anne-Sophie; Xiao, Tong; Bardakjian, Tanya; Schneider, Adele; Choi, Alex; Jorgenson, Eric; Baier, Herwig; El Sada, Mohamad; Schorderet, Daniel F; Slavotinek, Anne M

    2013-08-15

    The major active retinoid, all-trans retinoic acid, has long been recognized as critical for the development of several organs, including the eye. Mutations in STRA6, the gene encoding the cellular receptor for vitamin A, in patients with Matthew-Wood syndrome and anophthalmia/microphthalmia (A/M), have previously demonstrated the importance of retinol metabolism in human eye disease. We used homozygosity mapping combined with next-generation sequencing to interrogate patients with anophthalmia and microphthalmia for new causative genes. We used whole-exome and whole-genome sequencing to study a family with two affected brothers with bilateral A/M and a simplex case with bilateral anophthalmia and hypoplasia of the optic nerve and optic chiasm. Analysis of novel sequence variants revealed homozygosity for two nonsense mutations in ALDH1A3, c.568A>G, predicting p.Lys190*, in the familial cases, and c.1165A>T, predicting p.Lys389*, in the simplex case. Both mutations predict nonsense-mediated decay and complete loss of function. We performed antisense morpholino (MO) studies in Danio rerio to characterize the developmental effects of loss of Aldh1a3 function. MO-injected larvae showed a significant reduction in eye size, and aberrant axonal projections to the tectum were noted. We conclude that ALDH1A3 loss of function causes anophthalmia and aberrant eye development in humans and in animal model systems.

  7. 醛脱氢酶8A1融合蛋白的表达及其多克隆抗体的制备与鉴定

    Institute of Scientific and Technical Information of China (English)

    刘佳莹; 李淑珍; 李晓玲; 刘莹; 柳晓兰; 高建恩; 仲飞; 孙启鸿

    2008-01-01

    目的:重组表达醛脱氢酶8A1(aldehyde dehydrogenase 8 family member A1,ALDH8A1)蛋白,制备其多克隆抗体,并进行抗体的特异性鉴定,以及蛋白在组织和细胞内的定位.方法:以成人肝cDNA文库为模板,PCR扩增ALDH8A1目的片段,并构建重组表达载体pGEX- 4T-1-ALDH8A1和pET-32a-ALDH8A1,经测序鉴定插入载体的DNA片段序列正确后,转化大肠杆菌BL21,诱导表达GST-ALDH8A1和 His-ALDH8A1融合蛋白.经Western blot确定其为目的蛋白后,纯化重组融合蛋白,并以GST-ALDH8A1免疫家兔制备抗人ALDH8A1多克隆抗体.用His-ALDH8A1包板,ELISA法测定兔抗人ALDH8A1血清效价;Western blot鉴定兔抗人ALDH8A1血清在重组蛋白和天然蛋白中的反应特异性;免疫组化法确定ALDH8A1蛋白在组织和细胞中的定位.结果:成功构建重组表达载体pGEX- 4T-1-ALDH8A1和pET-32a-ALDH8A1;获得包涵体形式表达的GST-ALDH8A1和可溶性形式表达的 His-ALDH8A1融合蛋白;应用纯化的重组蛋白GST-ALDH8A1免疫家兔,获得兔抗人ALDH8A1血清,ELISA测定抗血清的效价为1∶ 256 000.Western blot结果显示,制备的ALDH8A1兔多抗可特异地识别成人肝总蛋白以及293T、 A549、 HeLa、 U937、 HepG2细胞总蛋白中一个相对分子质量(Mr)约53 000的ALDH8A1天然蛋白,与文献报道的ALDH8A1的Mr一致,表明ALDH8A1在正常肝组织与癌细胞中都有表达.免疫组化结果表明ALDH8A1蛋白定位于人肝癌细胞胞质中.结论:成功制备出兔抗人ALDH8A1多克隆抗体,此抗体可应用于ELISA,Western blot和免疫组化检测,为进一步研究ALDH8A1的功能奠定了基础.

  8. Antiangiogenic therapy using endostatin increases the number of ALDH+ lung cancer stem cells by generating intratumor hypoxia

    Science.gov (United States)

    Yu, Yang; Wang, Yu-yi; Wang, Yi-qin; Wang, Xia; Liu, Yan-Yang; Wang, Jian-Tao; Du, Chi; Wang, Li; Li, Mei; Luo, Feng; Jiang, Ming

    2016-01-01

    Antiangiogenic therapy is becoming a promising option for cancer treatment. However, many investigations have recently indicated that these therapies may have limited efficacy, and the cancers in most patients eventually develop resistance to these therapies. There is considerable recently acquired evidence for an association of such resistance with cancer stem-like cells (CSLCs). Here, we used xenograft tumor murine models to further suggest that antiangiogenic agents actually increase the invasive and metastatic properties of lung cancer cells. In our experiments with murine lung cancer xenografts, we found that the antiangiogenic agent endostatin increased the population of ALDH+ cells, and did so by generating intratumoral hypoxia in the xenografts. We further showed endostatin to cause an increase in the CSLC population by accelerating the generation of tumor hypoxia and by recruiting TAMs, MDSCs and Treg cells, which are inflammatory and immunosuppressive cells and which can secrete cytokines and growth factors such as IL-6, EGF, and TGF-β into the tumor microenvironment. All these factors are related with increased CSLC population in tumors. These results imply that improving the clinical efficacy of antiangiogenic treatments will require the concurrent use of CSLC-targeting agents. PMID:27703219

  9. Research advances in the catalysts for the selective oxidation of ethane to aldehydes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhe; ZHAO Zhen; XU Chunming

    2005-01-01

    Selective oxidation of ethane to aldehydes is one of the most difficult processes in the catalysis researches of low alkanes. The development of selective oxidation of ethane to aldehydes (formaldehyde, acetaldehyde and acrolein) is discussed. The latest progress of the catalysts, including bulk or supported metal oxide catalysts, highly dispersed and isolated active sites catalysts, and the photo-catalytic ethane oxidation catalysts, partial oxidation of ethane in the gas phase, and the proposed reaction pathways from ethane to aldehydes are involved.

  10. Detoxification of aldehydes by histidine-containing dipeptides: from chemistry to clinical implications

    OpenAIRE

    Xie, Zhengzhi; Baba, Shahid P.; Sweeney, Brooke R.; Barski, Oleg A.

    2013-01-01

    Aldehydes are generated by oxidized lipids and carbohydrates at increased levels under conditions of metabolic imbalance and oxidative stress during atherosclerosis, myocardial and cerebral ischemia, diabetes, neurodegenerative diseases and trauma. In most tissues, aldehydes are detoxified by oxidoreductases that catalyze the oxidation or the reduction of aldehydes or enzymatic and nonenzymatic conjugation with low molecular weight thiols and amines, such as glutathione and histidine dipeptid...

  11. An autosomal glucose-6-phosphate dehydrogenase (hexose-6-phosphate dehydrogenase) polymorphism in human saliva.

    Science.gov (United States)

    Tan, S G; Ashton, G C

    1976-01-01

    Glucose-6-phosphate dehydrogenase (hexose-6-phosphate dehydrogenase) from human saliva has been demonstrated by the zymogram technique. Three phenotypes were found. Family and population studies suggested that these phenotypes are the products of an autosomal locus with two alleles Sgd-1 and Sgd-2. PMID:950237

  12. Monolayer structures of alkyl aldehydes: Odd-membered homologues

    OpenAIRE

    Phillips, T. K.; Clarke, Stuart M.; Castro Arroyo, Miguel Ángel; Millán, Carmen; Medina, Santiago

    2011-01-01

    Crystalline monolayers of three aldehydes with an odd number of carbon atoms in the alkyl chain (C 7, C 9 and C 11) at low coverages are observed by a combination of X-ray and neutron diffraction. Analysis of the diffraction data is discussed and possible monolayer crystal structures are proposed; although unique structures could not be ascertained for all molecules. We conclude that the structures are flat on the surface, with the molecules lying in the plane of the layer. The C 11 homologue...

  13. Monolayer structures of alkyl aldehydes: Odd-membered homologues

    International Nuclear Information System (INIS)

    Crystalline monolayers of three aldehydes with an odd number of carbon atoms in the alkyl chain (C7, C9 and C11) at low coverages are observed by a combination of X-ray and neutron diffraction. Analysis of the diffraction data is discussed and possible monolayer crystal structures are proposed; although unique structures could not be ascertained for all molecules. We conclude that the structures are flat on the surface, with the molecules lying in the plane of the layer. The C11 homologue is determined to have a plane group of either p2, pgb or pgg, and for the C7 homologue the p2 plane group is preferred.

  14. Hydrogenations without Hydrogen: Titania Photocatalyzed Reductions of Maleimides and Aldehydes

    Directory of Open Access Journals (Sweden)

    David W. Manley

    2014-09-01

    Full Text Available A mild procedure for the reduction of electron-deficient alkenes and carbonyl compounds is described. UVA irradiations of substituted maleimides with dispersions of titania (Aeroxide P25 in methanol/acetonitrile (1:9 solvent under dry anoxic conditions led to hydrogenation and production of the corresponding succinimides. Aromatic and heteroaromatic aldehydes were reduced to primary alcohols in similar titania photocatalyzed reactions. A mechanism is proposed which involves two proton-coupled electron transfers to the substrates at the titania surface.

  15. Nuclear alkylated pyridine aldehyde polymers and conductive compositions thereof

    Science.gov (United States)

    Rembaum, A.; Singer, S. (Inventor)

    1970-01-01

    A thermally stable, relatively conductive polymer was disclosed. The polymer was synthesized by condensing in the presence of catalyst a 2, 4, or 6 nuclear alklylated 2, 3, or 4 pyridine aldehyde or quaternary derivatives thereof to form a polymer. The pyridine groups were liked by olefinic groups between 2-4, 2-6, 2-3, 3-4, 3-6 or 4-6 positions. Conductive compositions were prepared by dissolving the quaternary polymer and an organic charge transfer complexing agent such as TCNQ in a mutual solvent such as methanol.

  16. Microwave Assisted Solvent Free Synthesis of Azomethines from Aryl Aldehydes on Melamin Formaldehyde as Solid Support

    OpenAIRE

    Ramin Rezaei; Mohammadi, Mohammad K; Tahereh Ranjbar

    2011-01-01

    Various aryl aldehydes underwent prompt one pot conversion into the corresponding azomethines in high yields by reacting with hydroxylamine hydrochloride supported on melamine formaldehyde under microwave irradiation.

  17. Punishment sensitivity and tension reduction: Exploring the potential influence of genetics on South Korean alcohol consumption

    Directory of Open Access Journals (Sweden)

    Benjamin J. Mahoney

    2016-12-01

    Full Text Available Aldehyde dehydrogenase 2*2 (ALDH2*2 is a genetically mutated enzyme that affects the liver’s ability to break down acetaldehyde, resulting in immediate negative physical effects following alcohol consumption. This usually leads to reduced lifetime alcohol dependence rates among those with ALDH2*2. Paradoxically, while around 30% of South Koreans have ALDH2*2, they still maintain both high levels of alcohol consumption and dependence. Therefore, how the negative reactions to alcohol experienced by those with ALDH2*2 interact with the expected effects of alcohol and sensitivity to punishment is of interest. Four hundred and sixty South Korean university students were tested for the ALDH2 gene type and completed alcohol expectancy and sensitivity to reward/punishment measures. The results indicated that there are different predictors of alcohol consumption depending on gene type, with ALDH2*2 heavy drinkers exhibiting lower levels of SP and higher levels of tension reduction expectancy. These findings suggest that ALDH2*2 plays a central role in differences in motivation for alcohol consumption among South Koreans.

  18. Hairpin Ribozyme Genes Curtail Alcohol Drinking: from Rational Design to in vivo Effects in the Rat.

    Science.gov (United States)

    Sapag, Amalia; Irrazábal, Thergiory; Lobos-González, Lorena; Muñoz-Brauning, Carlos R; Quintanilla, María Elena; Tampier, Lutske

    2016-07-12

    Ribozyme genes were designed to reduce voluntary alcohol drinking in a rat model of alcohol dependence. Acetaldehyde generated from alcohol in the liver is metabolized by the mitochondrial aldehyde dehydrogenase (ALDH2) such that diminishing ALDH2 activity leads to the aversive effects of blood acetaldehyde upon alcohol intake. A stepwise approach was followed to design genes encoding ribozymes targeted to the rat ALDH2 mRNA. In vitro studies of accessibility to oligonucleotides identified suitable target sites in the mRNA, one of which fulfilled hammerhead and hairpin ribozyme requirements (CGGUC). Ribozyme genes delivered in plasmid constructs were tested in rat cells in culture. While the hairpin ribozyme reduced ALDH2 activity 56% by cleavage and blockade (P < 0.0001), the hammerhead ribozyme elicited minor effects by blockade. The hairpin ribozyme was tested in vivo by adenoviral gene delivery to UChB alcohol drinker rats. Ethanol intake was curtailed 47% for 34 days (P < 0.0001), while blood acetaldehyde more than doubled upon ethanol administration and ALDH2 activity dropped 25% in liver homogenates, not affecting other ALDH isoforms. Thus, hairpin ribozymes targeted to 16 nt in the ALDH2 mRNA provide durable and specific effects in vivo, representing an improvement on previous work and encouraging development of gene therapy for alcoholism.

  19. Radon and aldehyde concentrations in the indoor environment. Final report

    International Nuclear Information System (INIS)

    Findings regarding indoor air contaminants in the energy-efficient residence (EER) in Mt. Airy, Maryland are reported. The objectives of the study were to collect and analyze relevant air quality samples (specifically radon and aldehydes), characterize the indoor air quality with respect to radon and aldehydes, and develop relationships between air infiltration rates and contaminant levels. One-fifth of the measured formaldehyde concentrations were in the range that may cause health concerns. Although indoor temperature and relative humidity affect indoor HCHO concentration, the elevated formaldehyde concentrations were measured under very low air infiltration rates. The data show that ventilation of the indoor air space is somewhat effective in reducing high HCHO concentrations. The operation of the heat exchanger led to an increase of the air infiltration rate which in turn resulted in substantial reduction of formaldehyde concentrations. A considerable number of the collected samples of indoor air displayed radon concentrations at levels higher than 1.0 to 4.0 nCim-3 (assuming an equilibrium factor of 0.5, these radon levels would correspond to working levels above the health guidelines suggested by the US EPA for homes in Florida built on land reclaimed from phosphate mining). As in the case of indoor formaldehyde concentrations, elevated indoor concentrations are substantially reduced when the infiltration rate is increased. The data base shows that the use of the air to air heat exchanger leads to reduction of indoor radon concentration by increasing the residential ventilation rate

  20. Iodine-Catalyzed Prins Cyclization of Homoallylic Alcohols and Aldehydes

    Directory of Open Access Journals (Sweden)

    Luiz F. Silva

    2013-09-01

    Full Text Available The iodine-catalyzed Prins cyclization of homoallylic alcohols and aldehydes was investigated under metal-free conditions and without additives. Anhydrous conditions and inert atmosphere are not required. The reaction of 2-(3,4-dihydronaphthalen-1-ylpropan-1-ol and 21 aldehydes (aliphatic and aromatic in CH2Cl2 in the presence of 5 mol % of iodine gave 1,4,5,6-tetrahydro-2H-benzo[f]isochromenes in 54%–86% yield. Under similar conditions, the Prins cyclization of six alcohols containing an endocyclic double bond (primary, secondary, or tertiary led to dihydropyrans in 52%–91% yield. The acyclic homoallylic alcohols gave 4-iodo-tetrahydropyran in 29%–41% yield in the presence of 50 mol % of iodine. This type of substrate is the main limitation of the methodology. The relative configuration of the products was assigned by NMR and X-ray analysis. The mechanism and the ratio of the products are discussed, based on DFT calculations.

  1. Affinity chromatography of bacterial lactate dehydrogenases.

    Science.gov (United States)

    Kelly, N; Delaney, M; O'Carra, P

    1978-06-01

    The affinity system used was the immobilized oxamate derivative previously used to purify mammalian lactate dehydrogenases. The bacterial dehydrogenases specific for the L-stereoisomer of lactate behaved in the same way as the mammalian enzymes, binding strongly in the presence of NADH. The D-lactate-specific enzymes, however, did not show any biospecific affinity for this gel. The L-specific enzymes could be purified to homogeneity in one affinity-chromatographic step. The D-specific enzymes could be efficiently separated from the L-specific ones and could then be further purified on an immobilized NAD derivative. The mechanism of activation of the lactate dehydrogenase from Streptococcus faecalis by fructose 1,6-bisphosphate was investigated by using the immobilized oxamate gel. PMID:666726

  2. Inducible xylitol dehydrogenases in enteric bacteria.

    OpenAIRE

    Doten, R C; Mortlock, R P

    1985-01-01

    Morganella morganii ATCC 25829, Providencia stuartii ATCC 25827, Serratia marcescens ATCC 13880, and Erwinia sp. strain 4D2P were found to induce a xylitol dehydrogenase when grown on a xylitol-containing medium. The xylitol dehydrogenases were partially purified from the four strains, and those from M. morganii ATCC 25829, P. stuartii ATCC 25827, and S. marcescens ATCC 13880 were all found to oxidize xylitol to D-xylulose. These three enzymes had KmS for xylitol of 7.1 to 16.4 mM and molecul...

  3. A Novel NADPH-Dependent Aldehyde Reductase Gene from Saccharomyces cerevisiae NRRL Y-12632 Involved in the Detoxification of Aldehyde Inhibitors Derived from Lignocellulosic Biomass Conversion

    Science.gov (United States)

    Aldehyde inhibitors such as furfural, 5-hydroxymethylfurfural (HMF), anisaldehyde, benzaldehyde, cinnamaldehyde, and phenylaldehyde are commonly generated during lignocellulosic biomass conversion process for low-cost cellulosic ethanol production that interferes with subsequent microbial growth and...

  4. Threshold responses in cinnamic-aldehyde-sensitive subjects: results and methodological aspects

    DEFF Research Database (Denmark)

    Johansen, J D; Andersen, Klaus Ejner; Rastogi, S C;

    1996-01-01

    Cinnamic aldehyde is an important fragrance material and contact allergen. The present study was performed to provide quantitative data on the eliciting capacity of cinnamic aldehyde, to be considered in assessment of clinical relevance and health hazard. The skin response to serial dilution patc...

  5. Catalytic Fehling's Reaction: An Efficient Aerobic Oxidation of Aldehyde Catalyzed by Copper in Water.

    Science.gov (United States)

    Liu, Mingxin; Li, Chao-Jun

    2016-08-26

    The first example of homogeneous copper-catalyzed aerobic oxidation of aldehydes is reported. This method utilizes atmospheric oxygen as the sole oxidant, proceeds under extremely mild aqueous conditions, and covers a wide range of various functionalized aldehydes. Chromatography is generally not necessary for product purification. PMID:27505714

  6. Direct chemoselective synthesis of glyconanoparticles from unprotected reducing glycans and glycopeptide aldehydes

    DEFF Research Database (Denmark)

    Thygesen, Mikkel Boas; Sørensen, Kasper Kildegaard; Cló, Emiliano;

    2009-01-01

    Chemoselective oxime coupling was used for facile conjugation of unprotected, reducing glycans and glycopeptide aldehydes with core-shell gold nanoparticles carrying reactive aminooxy groups on the organic shell.......Chemoselective oxime coupling was used for facile conjugation of unprotected, reducing glycans and glycopeptide aldehydes with core-shell gold nanoparticles carrying reactive aminooxy groups on the organic shell....

  7. Draft Genome Sequence of Aldehyde-Degrading Strain Halomonas axialensis ACH-L-8

    OpenAIRE

    Ye, Jun; Ren, Chong; Shan, Xiexie; Zeng, Runying

    2016-01-01

    Halomonas axialensis ACH-L-8, a deep-sea strain isolated from the South China Sea, has the ability to degrade aldehydes. Here, we present an annotated draft genome sequence of this species, which could provide fundamental molecular information on the aldehydes-degrading mechanism.

  8. Draft Genome Sequence of Aldehyde-Degrading Strain Halomonas axialensis ACH-L-8.

    Science.gov (United States)

    Ye, Jun; Ren, Chong; Shan, Xiexie; Zeng, Runying

    2016-01-01

    Halomonas axialensisACH-L-8, a deep-sea strain isolated from the South China Sea, has the ability to degrade aldehydes. Here, we present an annotated draft genome sequence of this species, which could provide fundamental molecular information on the aldehydes-degrading mechanism. PMID:27081145

  9. Yeast surface display of dehydrogenases in microbial fuel-cells.

    Science.gov (United States)

    Gal, Idan; Schlesinger, Orr; Amir, Liron; Alfonta, Lital

    2016-12-01

    Two dehydrogenases, cellobiose dehydrogenase from Corynascus thermophilus and pyranose dehydrogenase from Agaricus meleagris, were displayed for the first time on the surface of Saccharomyces cerevisiae using the yeast surface display system. Surface displayed dehydrogenases were used in a microbial fuel cell and generated high power outputs. Surface displayed cellobiose dehydrogenase has demonstrated a midpoint potential of -28mV (vs. Ag/AgCl) at pH=6.5 and was used in a mediator-less anode compartment of a microbial fuel cell producing a power output of 3.3μWcm(-2) using lactose as fuel. Surface-displayed pyranose dehydrogenase was used in a microbial fuel cell and generated high power outputs using different substrates, the highest power output that was achieved was 3.9μWcm(-2) using d-xylose. These results demonstrate that surface displayed cellobiose dehydrogenase and pyranose dehydrogenase may successfully be used in microbial bioelectrochemical systems.

  10. Yeast surface display of dehydrogenases in microbial fuel-cells.

    Science.gov (United States)

    Gal, Idan; Schlesinger, Orr; Amir, Liron; Alfonta, Lital

    2016-12-01

    Two dehydrogenases, cellobiose dehydrogenase from Corynascus thermophilus and pyranose dehydrogenase from Agaricus meleagris, were displayed for the first time on the surface of Saccharomyces cerevisiae using the yeast surface display system. Surface displayed dehydrogenases were used in a microbial fuel cell and generated high power outputs. Surface displayed cellobiose dehydrogenase has demonstrated a midpoint potential of -28mV (vs. Ag/AgCl) at pH=6.5 and was used in a mediator-less anode compartment of a microbial fuel cell producing a power output of 3.3μWcm(-2) using lactose as fuel. Surface-displayed pyranose dehydrogenase was used in a microbial fuel cell and generated high power outputs using different substrates, the highest power output that was achieved was 3.9μWcm(-2) using d-xylose. These results demonstrate that surface displayed cellobiose dehydrogenase and pyranose dehydrogenase may successfully be used in microbial bioelectrochemical systems. PMID:27459246

  11. Synthesis of bio-based aldehyde from seaweed polysaccharide and its interaction with bovine serum albumin.

    Science.gov (United States)

    Kholiya, Faisal; Chaudhary, Jai Prakash; Vadodariya, Nilesh; Meena, Ramavatar

    2016-10-01

    Here, we demonstrate a successful synthesis of bio-based aldehyde namely dialdehyde-carboxymethylagarose (DCMA) using carboxymethyagarose (CMA). Further reaction parameters (i.e. reaction temperature, pH and periodate concentration) were optimized to achieve maximum aldehyde content and product yield. The synthesis of DCMA was confirmed by employing FTIR, (1)H NMR, XRD, SEM, AFM, TGA, DSC, EA and GPC techniques. To investigate the aldehyde functionality, DCMA was allowed to interact with BSA and obtained results were found to be comparable with that of synthetic aldehyde (Formaldehyde). Further interaction of DCMA with BSA was confirmed by using UV-vis, FTIR, fluorescent spectroscopy, CD and DLS analysis. Results of this study revealed that bio-based aldehyde behaves like formaldehyde. This study adds value to abundant marine biopolymers and opens the new research area for polymer researchers. PMID:27312639

  12. Optimization of Adsorptive Immobilization of Alcohol Dehydrogenases

    NARCIS (Netherlands)

    Trivedi, Archana; Heinemann, Matthias; Spiess, Antje C.; Daussmann, Thomas; Büchs, Jochen

    2005-01-01

    In this work, a systematic examination of various parameters of adsorptive immobilization of alcohol dehydrogenases (ADHs) on solid support is performed and the impact of these parameters on immobilization efficiency is studied. Depending on the source of the enzymes, these parameters differently in

  13. DNA-Templated Introduction of an Aldehyde Handle in Proteins

    DEFF Research Database (Denmark)

    Kodal, Anne Louise Bank; Rosen, Christian Bech; Mortensen, Michael Rosholm;

    2016-01-01

    Many medical and biotechnological applications rely on labeling of proteins, but one key challenge is the production of homogeneous and site-specific conjugates. This can rarely be achieved by mere residue-specific random labeling, but requires genetic engineering. Using site-selective DNA......-templated reductive amination we create DNA-protein conjugates with control over labeling stoichiometry without genetic engineering. A guiding DNA strand with a metal-binding functionality facilitates site-selectivity by directing coupling of a second reactive DNA strand to the vicinity of a protein metal......-binding site. Here, we demonstrate DNA-templated reductive amination for His6-tagged proteins and native metal-binding proteins, including IgG1 antibodies. We also use a cleavable linker between the DNA and the protein to remove the DNA and introduce a single aldehyde to proteins. This functions as a handle...

  14. Monolayer structures of alkyl aldehydes: Odd-membered homologues

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, T.K. [BP Institute, Department of Chemistry, University of Cambridge, Cambridge (United Kingdom); Clarke, S.M., E-mail: stuart@bpi.cam.ac.u [BP Institute, Department of Chemistry, University of Cambridge, Cambridge (United Kingdom); Bhinde, T. [BP Institute, Department of Chemistry, University of Cambridge, Cambridge (United Kingdom); Castro, M.A.; Millan, C. [Instituto Ciencia de los Materiales de Sevilla, Departamento de Quimica Inorganica (CSIC-Universidad de Sevilla) (Spain); Medina, S. [Centro de Investigacion, Tecnologia e Innovacion de la Universidad de Sevilla (CITIUS), Sevilla (Spain)

    2011-03-01

    Crystalline monolayers of three aldehydes with an odd number of carbon atoms in the alkyl chain (C{sub 7}, C{sub 9} and C{sub 11}) at low coverages are observed by a combination of X-ray and neutron diffraction. Analysis of the diffraction data is discussed and possible monolayer crystal structures are proposed; although unique structures could not be ascertained for all molecules. We conclude that the structures are flat on the surface, with the molecules lying in the plane of the layer. The C{sub 11} homologue is determined to have a plane group of either p2, pgb or pgg, and for the C{sub 7} homologue the p2 plane group is preferred.

  15. Reduction of Aldehydes and Ketones with Potassium Borohydride as Reductant

    Institute of Scientific and Technical Information of China (English)

    罗慧谋; 李毅群

    2005-01-01

    A series of aldehydes and ketones were reduced by potassium borohydride in an ionic liquid/water ([bmim]PF6/H2O) biphasic system to afford corresponding alcohol with high purity in excellent yields. The ionic liquid/water biphasic system could promote the chemoselectivity and the substituents such as nitro group and chlorine remained intact. Aromatic ketones were not as active as aromatic aldhydes and cyclic ketones owing to their higher steric hindrance. The ionic liquid could be recycled and reused. This protocol has notable advantages of no need of phase transfer catalyst and organic solvents, mild conditions, simple operation, short reaction time, ease work-up, high yields and recycling of the ionic liquid.

  16. Pharmacological activities of cilantro's aliphatic aldehydes against Leishmania donovani.

    Science.gov (United States)

    Donega, Mateus A; Mello, Simone C; Moraes, Rita M; Jain, Surendra K; Tekwani, Babu L; Cantrell, Charles L

    2014-12-01

    Leishmaniasis is a chronic infectious disease caused by different Leishmania species. Global occurrences of this disease are primarily limited to tropical and subtropical regions. Treatments are available; however, patients complain of side effects. Different species of plants have been screened as a potential source of new drugs against leishmaniasis. In this study, we investigated the antileishmanial activity of cilantro (Coriandrum sativum) essential oil and its main components: (E)-2-undecenal, (E)-2-decenal, (E)-2-dodecenal, decanal, dodecanal, and tetradecanal. The essential oil of C. sativum leaves inhibits growth of Leishmani donovani promastigotes in culture with an IC50 of 26.58 ± 6.11 µg/mL. The aliphatic aldehydes (E)-2-decenal (7.85 ± 0.28 µg/mL), (E)-2-undecenal (2.81 ± 0.21 µg/mL), and (E)-2-dodecenal (4.35 ± 0.15 µg/mL), all isolated from C. sativum essential oil, are effective inhibitors of in vitro cultures of L. donovani promastigotes. Aldehydes (E)-2-decenal, (E)-2-undecenal, and (E)-2-dodecenal were also evaluated against axenic amastigotes and IC50 values were determined to be 2.47 ± 0.25 µg/mL, 1.25 ± 0.11 µg/mL, and 4.78 ± 1.12 µg/mL, respectively. (E)-2-Undecenal and (E)-2-dodecenal demonstrated IC50 values of 5.65 ± 0.19 µg/mL and 9.60 ± 0.89 µg/mL, respectively, against macrophage amastigotes. These cilantro compounds showed no cytotoxicity against THP-1 macrophages. PMID:25340465

  17. Quantification of Carnosine-Aldehyde Adducts in Human Urine.

    Science.gov (United States)

    da Silva Bispo, Vanderson; Di Mascio, Paolo; Medeiros, Marisa

    2014-10-01

    Lipid peroxidation generates several reactive carbonyl species, including 4-hydroxy-2-nonenal (HNE), acrolein (ACR), 4-hydroxy-2-hexenal (HHE) and malondialdehyde. One major pathwayof aldehydes detoxification is through conjugation with glutathione catalyzed by glutathione-S-transferases or, alternatively, by conjugation with endogenous histidine containing dipeptides, such as carnosine (CAR). In this study, on-line reverse-phase high-performance liquid chromatography (HPLC) separation with tandem mass spectrometry detection was utilized for the accurate quantification of CAR- ACR, CAR-HHE and CAR-HNE adducts in human urinary samples from non-smokers young adults. Standard adducts were prepared and isolated by HPLC. The results showed the presence of a new product from the reaction of CAR with ACR. This new adduct was completely characterized by HPLC/MS-MSn, 1H RMN, COSY and HSQC. The new HPLC/MS/MS methodology employing stable isotope-labeled internal standards (CAR-HHEd5 and CAR-HNEd11) was developed for adducts quantification. This methodology permits quantification of 10pmol CAR-HHE and 1pmol of CAR-ACR and CAR-HNE. Accurate determinations in human urine sample were performed and showed 4.65±1.71 to CAR-ACR, 5.13±1.76 to CAR-HHE and 5.99±3.19nmol/mg creatinine to CAR-HNE. Our results indicate that carnosine pathways can be an important detoxification route of a, ß -unsaturated aldehydes. Moreover, carnosine adducts may be useful as redox stress indicator. PMID:26461323

  18. Characterization of xylitol dehydrogenase from Debaryomyces hansenii

    Energy Technology Data Exchange (ETDEWEB)

    Girio, F.M.; Amaral-Collaco, M.T. [INETI, Lisboa (Portugal); Pelica, F. [ITQB, Oeiras (Portugal)

    1996-01-01

    The xylitol dehydrogenase (EC 1.1.1.9) from xylose-grown cells of Debaryomyces hansenii was partially purified in two chromatographic steps, and characterization studies were carried out in order to investigate the role of the xylitol dehydrogenase-catalyzed step in the regulation of D-xylose metabolism. The enzyme was most active at pH 9.0-9.5, and exhibited a broad polyol specificity. The Michaelis constants for xylitol and NAD{sup +} were 16.5 and 0.55 mM, respectively. Ca{sup 2+}, Mg{sup 2+}, and Mn{sup 2+} did not affect the enzyme activity. Conversely, Zn{sup 2+}, Cd{sup 2+}, and Co{sup 2+} strongly inhibited the enzyme activity. It was concluded that NAD{sup +}-xylitol dehydrogenase from D. hansenii has similarities with other xylose-fermenting yeasts in respect to optimal pH, substrate specificity, and K{sub m} value for xylitol, and therefore should be named L-iditol:NAD{sup +}-5-oxidoreductase (EC 1.1.1.14). The reason D. hansenii is a good xylitol producer is not because of its value of K for xylitol, which is low enough to assure its fast oxidation by NAD{sup +}-xylitol dehydrogenase. However, a higher K{sub m} value of xylitol dehydrogenase for NAD{sup +} compared to the K{sub m} values of other xylose-fermenting yeasts may be responsible for the higher xylitol yields. 22 refs., 4 figs., 2 tabs.

  19. Transcriptome analysis of Zymomonas mobilis ZM4 reveals mechanisms of tolerance and detoxification of phenolic aldehyde inhibitors from lignocellulose pretreatment

    OpenAIRE

    Yi, Xia; Gu, Hanqi; Gao, Qiuqiang; Liu, Z. Lewis; Bao, Jie

    2015-01-01

    Background Phenolic aldehydes generated from lignocellulose pretreatment exhibited severe toxic inhibitions on microbial growth and fermentation. Numerous tolerance studies against furfural, 5-hydroxymethyl-2-furaldehyde (HMF), acetate, and ethanol were reported, but studies on inhibition of phenolic aldehyde inhibitors are rare. For ethanologenic strains, Zymomonas mobilis ZM4 is high in ethanol productivity and genetic manipulation feasibility, but sensitive to phenolic aldehyde inhibitors....

  20. Effects and action mechanisms of Korean pear (Pyrus pyrifolia cv. Shingo) on alcohol detoxification.

    Science.gov (United States)

    Lee, Ho-Sun; Isse, Toyoshi; Kawamoto, Toshihiro; Woo, Hyun-Su; Kim, An Keun; Park, Jong Y; Yang, Mihi

    2012-11-01

    Korean pear (Pyrus pyrifolia cv. Shingo) has been used as a traditional medicine for alleviating alcohol hangover. However, scientific evidence for its effectiveness or mechanism is not clearly established. To investigate its mechanism of alcohol detoxification, both in vitro and in vivo studies were performed with an aldehyde dehydrogenase 2 (ALDH2) alternated animal model. The pear extract (10 mL/kg bw) was administered to Aldh2 normal (C57BL/6) and deficient (Aldh2 -/-) male mice. After 30 min, ethanol (1 g or 2 g/kg bw) was administered to the mice via gavage. Levels of alcohol and acetaldehyde in blood were quantified by GC/MS. First, it was observed that the pears stimulated both alcohol dehydrogenase (ADH) and ALDH activities by 2∼3-  and 1.3-fold in in vitro studies, respectively. Second, mouse PK data (AUC(∞) and C(max) ) showed that the pear extract decreased the alcohol level in blood regardless of ALDH2 genotype. Third, the pear increased the acetaldehyde level in blood in Aldh2 deficient mice but not in Aldh2 normal mice. Therefore, the consistent in vitro and in vivo data suggest that Korean pears stimulate the two key alcohol-metabolizing enzymes. These stimulations could be the main mechanism of the Korean pear for alcohol detoxification. Finally, the results suggest that polymorphisms of human ALDH2 could bring out individual variations in the effects of Korean pear on alcohol detoxification. PMID:22451246

  1. Functional analysis of a cinnamyl alcohol dehydrogenase involved in lignin biosynthesis in wheat.

    Science.gov (United States)

    Ma, Qing-Hu

    2010-06-01

    Cinnamyl alcohol dehydrogenase (CAD) catalyses the final step in the biosynthesis of monolignols. In the present study, a cDNA encoding a CAD was isolated from wheat, designated as TaCAD1. A genome-wide data mining in the wheat EST database revealed another 10 CAD-like homologues, namely TaCAD2 to TaCAD11. A phylogenetic analysis showed that TaCAD1 belonged to the bona fide CAD group involved in lignin synthesis. Two other putative CADs from the wheat genome (TaCAD2 and TaCAD4) also belonged to this group and were very close to TaCAD1, but lacked C-terminal domain, suggesting that they are pseudogenes. DNA gel blot analysis for the wheat genome showed two to three copies of CAD related to TaCAD1, but RNA gel blot analysis revealed only single band for TaCAD1, which was highly expressed in stem, with quite low expression in leaf and undetectable expression in root. The predicted three-dimension structure of TaCAD1 resembled that of AtCAD5, but two amino acid substitutions were identified in the substrate binding region. Recombinant TaCAD1 protein used coniferyl aldehyde as the most favoured substrate, also showed high efficiencies toward sinapyl and p-coumaryl aldehydes. TaCAD1 was an enzyme being pH-dependent and temperature-sensitive, and showing a typical random catalysing mechanism. At the milky stage of wheat, TaCAD1 mRNA abundance, protein level and enzyme activity in stem tissues were higher in a lodging-resistant cultivar (H4546) than in lodging-sensitive cultivar (C6001). These properties were correlated to the lignin contents and lodging indices of the two cultivars. These data suggest that TaCAD1 is the predominant CAD in wheat stem for lignin biosynthesis and is critical for lodging resistance.

  2. α,β-Unsaturated aldehyde of hyaluronan--Synthesis, analysis and applications.

    Science.gov (United States)

    Buffa, Radovan; Šedová, Petra; Basarabová, Ivana; Moravcová, Martina; Wolfová, Lucie; Bobula, Tomáš; Velebný, Vladimír

    2015-12-10

    Hyaluronic acid (HA) modified with an aldehyde group (HA-CHO or HA-aldehyde) has been extensively used for various biomedical applications. The main advantage of the aldehyde moieties is the ability to react with a wide range of amino compounds under physiological conditions. Reactions of aldehydes with primary amines in water are reversible and equilibrium is thoroughly shifted towards starting aldehyde and amine. This work presents an unique modification of HA: α,β-unsaturated aldehyde of HA (4,5-anhydro-6(GlcNAc)-oxo HA or ΔHA-CHO), which allows the primary amines to be attached to HA more effectively in comparison to the saturated HA-CHO. Higher hydrolytic stability is caused by the conjugation of imine with an adjacent --C=C-- double bond. Two strategies for the preparation of unsaturated HA-aldehyde were developed and chemical structures were studied in details. Cross-linked materials prepared from this precursor are biocompatible and suitable for applications in drug delivery and regenerative medicine. PMID:26428127

  3. Disruption of seven hypothetical aryl alcohol dehydrogenase genes from Saccharomyces cerevisiae and construction of a multiple knock-out strain.

    Science.gov (United States)

    Delneri, D; Gardner, D C; Bruschi, C V; Oliver, S G

    1999-11-01

    By in silicio analysis, we have discovered that there are seven open reading frames (ORFs) in Saccharomyces cerevisiae whose protein products show a high degree of amino acid sequence similarity to the aryl alcohol dehydrogenase (AAD) of the lignin-degrading fungus Phanerochaete chrysosporium. Yeast cultures grown to stationary phase display a significant aryl alcohol dehydrogenase activity by degrading aromatic aldehydes to the corresponding alcohols. To study the biochemical and the biological role of each of the AAD genes, a series of mutant strains carrying deletion of one or more of the AAD-coding sequences was constructed by PCR-mediated gene replacement, using the readily selectable marker kanMX. The correct targeting of the PCR-generated disruption cassette into the genomic locus was verified by analytical PCR and by pulse-field gel electrophoresis (PFGE) followed by Southern blot analysis. Double, triple and quadruple mutant strains were obtained by classical genetic methods, while the construction of the quintuple, sextuple and septuple mutants was achieved by using the marker URA3 from Kluyveromyces lactis, HIS3 from Schizosaccharomyces pombe and TRP1 from S. cerevisiae. None of the knock-out strains revealed any mutant phenotype when tested for the degradation of aromatic aldehydes using both spectrophotometry and high performance liquid chromatography (HPLC). Specific tests for changes in the ergosterol and phospholipids profiles did not reveal any mutant phenotype and mating and sporulation efficiencies were not affected in the septuple deletant. Compared to the wild-type strain, the septuple deletant showed an increased resistance to the anisaldehyde, but there is a possibility that the nutritional markers used for gene replacement are causing this effect.

  4. A missense mutation in ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), causes an autosomal recessive neurocutaneous syndrome.

    Science.gov (United States)

    Bicknell, Louise S; Pitt, James; Aftimos, Salim; Ramadas, Ram; Maw, Marion A; Robertson, Stephen P

    2008-10-01

    There are several rare syndromes combining wrinkled, redundant skin and neurological abnormalities. Although phenotypic overlap between conditions has suggested that some might be allelic to one another, the aetiology for many of them remains unknown. A consanguineous New Zealand Maori family has been characterised that segregates an autosomal recessive connective tissue disorder (joint dislocations, lax skin) associated with neurological abnormalities (severe global developmental delay, choreoathetosis) without metabolic abnormalities in four affected children. A genome-screen performed under a hypothesis of homozygosity by descent for an ancestral mutation, identified a locus at 10q23 (Z = 3.63). One gene within the candidate interval, ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), was considered a plausible disease gene since a missense mutation had previously been shown to cause progressive neurodegeneration, cataracts, skin laxity, joint dislocations and metabolic derangement in a consanguineous Algerian family. A missense mutation, 2350C>T, was identified in ALDH18A1, which predicts the substitution H784Y. H784 is invariant across all phyla and lies within a previously unrecognised, conserved C-terminal motif in P5CS. In an in vivo assay of flux through this metabolic pathway using dermal fibroblasts obtained from an affected individual, proline and ornithine biosynthetic activity of P5CS was not affected by the H784Y substitution. These data suggest that P5CS may possess additional uncharacterised functions that affect connective tissue and central nervous system function.

  5. Antimony(v) cations for the selective catalytic transformation of aldehydes into symmetric ethers, α,β-unsaturated aldehydes, and 1,3,5-trioxanes.

    Science.gov (United States)

    Arias Ugarte, Renzo; Devarajan, Deepa; Mushinski, Ryan M; Hudnall, Todd W

    2016-07-01

    1-Diphenylphosphinonaphthyl-8-triphenylstibonium triflate ([][OTf]) was prepared in excellent yield by treating 1-lithio-8-diphenylphosphinonaphthalene with dibromotriphenylstiborane followed by halide abstraction with AgOTf. This antimony(v) cation was found to be stable toward oxygen and water, and exhibited exceptional Lewis acidity. The Lewis acidity of [][OTf] was exploited in the catalytic reductive coupling of a variety of aldehydes into symmetric ethers of type in good to excellent yields under mild conditions using Et3SiH as the reductant. Additionally, [][OTf] was found to selectively catalyze the Aldol condensation reaction to afford α-β unsaturated aldehydes () when aldehydes with 2 α-hydrogen atoms were used. Finally, [][OTf] catalyzed the cyclotrimerization of aliphatic and aromatic aldehydes to afford the industrially-useful 1,3,5 trioxanes () in good yields, and with great selectivity. This phosphine-stibonium motif represents one of the first catalytic systems of its kind that is able to catalyze these reactions with aldehydes in a controlled, efficient manner. The mechanism of these processes has been explored both experimentally and theoretically. In all cases the Lewis acidic nature of the antimony(v) cation was found to promote these reactions. PMID:27326797

  6. The carbonyl oxide-aldehyde complex: a new intermediate of the ozonolysis reaction

    Science.gov (United States)

    Cremer, Dieter; Kraka, Elfi; McKee, M. L.; Radharkrishnan, T. P.

    1991-12-01

    MP4(SDQ)/6-31G (d,p) calculations suggest that the ozonolysis of alkenes in solution phase does not proceed via carbonyl oxide, but via a dipole complex between aldehyde and carbonyl oxide, which is 9 kcal/mol more stable than the separated molecules. The dipole complex is probably formed in the solvent cage upon decomposition of primary ozonide to aldehyde and carbonyl oxide. Rotation of either aldehyde or carbonyl oxide in the solvent cage leads to an antiparallel alignment of molecular dipole moments and dipole-dipole attraction.

  7. Transformations of several monoterpenoids in the presence of aldehydes in supercritical solvents

    Science.gov (United States)

    Anikeev, V. I.; Sivcev, V. P.; Il'ina, I. V.; Korchagina, D. V.; Statsenko, O. B.; Volcho, K. P.; Salakhutdinov, N. F.

    2013-03-01

    The reactivity of verbenol epoxide and isopulegol in supercritical solvents in the presence of aromatic aldehydes was studied using a flow type reactor and a heterogeneous catalyst (Al2O3) or no catalyst. The intramolecular transformations or interactions of reagents with the solvent prevailed in all cases; the yield of the products of intermolecular reactions of terpenoids with aldehydes was up to 1%. The aldehydes did not interact with verbenol epoxide but produced a considerable effect on the distribution of its isomerization products.

  8. MOLECULAR MODELLING OF HUMAN ALDEHYDE OXIDASE AND IDENTIFICATION OF THE KEY INTERACTIONS IN THE ENZYME-SUBSTRATE COMPLEX

    Directory of Open Access Journals (Sweden)

    Siavoush Dastmalchi

    2005-05-01

    Full Text Available Aldehyde oxidase (EC 1.2.3.1, a cytosolic enzyme containing FAD, molybdenum and iron-sulphur cluster, is a member of non-cytochrome P-450 enzymes called molybdenum hydroxylases which is involved in the metabolism of a wide range of endogenous compounds and many drug substances. Drug metabolism is one of the important characteristics which influences many aspects of a therapeutic agent such as routes of administration, drug interaction and toxicity and therefore, characterisation of the key interactions between enzymes and substrates is very important from drug development point of view. The aim of this study was to generate a three-dimensional model of human aldehyde oxidase (AO in order to assist us to identify the mode of interaction between enzyme and a set of phethalazine/quinazoline derivatives. Both sequence-based (BLAST and inverse protein fold recognition methods (THREADER were used to identify the crystal structure of bovine xanthine dehydrogenase (pdb code of 1FO4 as the suitable template for comparative modelling of human AO. Model structure was generated by aligning and then threading the sequence of human AO onto the template structure, incorporating the associated cofactors, and molecular dynamics simulations and energy minimization using GROMACS program. Different criteria which were measured by the PROCHECK, QPACK, VERIFY-3D were indicative of a proper fold for the predicted structural model of human AO. For example, 97.9 percentages of phi and psi angles were in the favoured and most favoured regions in the ramachandran plot, and all residues in the model are assigned environmentally positive compatibility scores. Further evaluation on the model quality was performed by investigation of AO-mediated oxidation of a set of phthalazine/quinazoline derivatives to develop QSAR model capable of describing the extent of the oxidation. Substrates were aligned by docking onto the active site of the enzyme using GOLD technology and then

  9. Studies of aldehydes in an atmosphere simulation chamber

    Energy Technology Data Exchange (ETDEWEB)

    Bossmeyer, J.

    2006-05-15

    recommendations at near-ambient concentration levels. However, the measured yields of the product aldehydes in the NO{sub 3} reactions with propanal and butanal disagreed with model calculations. This discrepancy originated from the model assumptions made for the kinetics of peroxyacyl nitrates in the degradation mechanism of the aldehydes. (orig.)

  10. Dihydrodiol dehydrogenase and polycyclic aromatic hydrocarbon metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Smithgall, T.E.

    1986-01-01

    Carcinogenic activation of polycyclic aromatic hydrocarbons by microsomal monoxygenases proceeds through trans-dihydrodiol metabolites to diol-epoxide ultimate carcinogens. This thesis directly investigated the role of dihydrodiol dehydrogenase, a cytosolic NAD(P)-linked oxidoreductase, in the detoxification of polycyclic aromatic trans-dihydrodiols. A wide variety of non-K-region trans-dihydrodiols were synthesized and shown to be substrates for the homogeneous rat liver dehydrogenase, including several potent proximate carcinogens derived from 7,12-dimethylbenz(a)anthracene, 5-methylchrysene, and benzo(a)pyrene. Since microsomal activation of polycyclic aromatic hydrocarbons is highly stereospecific, the stereochemical course of enzymatic trans-dihydrodiol oxidation was monitored using circular dichroism spectropolarimetry. The major product formed from the dehydrogenase-catalyzed oxidation of the trans-1,2-dihydrodiol of naphthalene was characterized using UV, IR, NMR, and mass spectroscopy, and appears to be 4-hydroxy-1,2-naphthoquinone. Mass spectral analysis suggests that an analogous hydroxylated o-quinone is formed as the major product of benzo(a)pyrene-7,8-dihydrodiol oxidation. Enzymatic oxidation of trans-dihydrodiols was shown to be potently inhibited by all of the major classes of the nonsteroidal antiinflammatory drugs. Enhancement of trans-dihydrodiol proximate carcinogen oxidation may protect against possible adverse effects of the aspirin-like drugs, and help maintain the balance between activation and detoxification of polycyclic aromatic hydrocarbons.

  11. Coniferyl Aldehyde Ameliorates Radiation Intestine Injury via Endothelial Cell Survival

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Ye Ji; Jung, Myung Gu; Lee, Yoonjin; Lee, Haejune [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yunsil [Ewha Woman' s Univ., Seoul (Korea, Republic of); Ko, Younggyu [Korea Univ., Seoul (Korea, Republic of)

    2014-05-15

    Cancer treatments related gastrointestinal toxicity has also been recognized as a significant economic burden. Especially, extensive apoptosis of microvascular endothelial cell of the lamina propria is the primary lesion initiating intestinal radiation damage after abdominal radiation therapy. Coniferyl aldehyde (CA) is phenolic compounds isolated from cork stoppers, and one of the major pyrolysis products of lignin. Shi H. was support for the empirical use of CA as a medicinal food for cardiovascular diseases. CA has positive effect in broad way but there is no consequence in radiation induced intestine damage. Here, we investigate effect of CA on small intestine after abdominal IR to mice in this study. In this study, CA increased the survival rate in C3H mice against 13.5 Gy abdominal IR. We found CA protects small intestine via preventing endothelial cell apoptosis and enhancing their angiogenic activity. CA also showed protective effect on crypt cell survival. Endothelial cell survival may affect crypt cell protection against IR. From this data, we concluded that CA is effective for protection against abdominal radiation injury. CA could ameliorate side-effect of radiation therapy.

  12. Does acute exposure to aldehydes impair pulmonary function and structure?

    Science.gov (United States)

    Abreu, Mariana de; Neto, Alcendino Cândido; Carvalho, Giovanna; Casquillo, Natalia Vasconcelos; Carvalho, Niedja; Okuro, Renata; Ribeiro, Gabriel C Motta; Machado, Mariana; Cardozo, Aléxia; Silva, Aline Santos E; Barboza, Thiago; Vasconcellos, Luiz Ricardo; Rodrigues, Danielle Araujo; Camilo, Luciana; Carneiro, Leticia de A M; Jandre, Frederico; Pino, Alexandre V; Giannella-Neto, Antonio; Zin, Walter A; Corrêa, Leonardo Holanda Travassos; Souza, Marcio Nogueira de; Carvalho, Alysson R

    2016-07-15

    Mixtures of anhydrous ethyl alcohol and gasoline substituted for pure gasoline as a fuel in many Brazilian vehicles. Consequently, the concentrations of volatile organic compounds (VOCs) such as ketones, other organic compounds, and particularly aldehydes increased in many Brazilian cities. The current study aims to investigate whether formaldehyde, acetaldehyde, or mixtures of both impair lung function, morphology, inflammatory and redox responses at environmentally relevant concentrations. For such purpose, C57BL/6 mice were exposed to either medical compressed air or to 4 different mixtures of formaldehyde and acetaldehyde. Eight hours later animals were anesthetized, paralyzed and lung mechanics and morphology, inflammatory cells and IL-1β, KC, TNF-α, IL-6, CCL2, MCP-1 contents, superoxide dismutase and catalalase activities were determined. The extra pulmonary respiratory tract was also analyzed. No differences could be detected between any exposed and control groups. In conclusion, no morpho-functional alterations were detected in exposed mice in relation to the control group. PMID:27102012

  13. Sodium borohydride removes aldehyde inhibitors for enhancing biohydrogen fermentation.

    Science.gov (United States)

    Lin, Richen; Cheng, Jun; Ding, Lingkan; Song, Wenlu; Zhou, Junhu; Cen, Kefa

    2015-12-01

    To enhance biohydrogen production from glucose and xylose in the presence of aldehyde inhibitors, reducing agent (i.e., sodium borohydride) was in situ added for effective detoxification. The detoxification efficiencies of furfural (96.7%) and 5-hydroxymethylfurfural (5-HMF, 91.7%) with 30mM NaBH4 were much higher than those of vanillin (77.3%) and syringaldehyde (69.3%). Biohydrogen fermentation was completely inhibited without detoxification, probably because of the consumption of nicotinamide adenine dinucleotide (NADH) by inhibitors reduction (R-CHO+2NADH→R-CH2OH+2NAD(+)). Addition of 30mM NaBH4 provided the reducing power necessary for inhibitors reduction (4R-CHO+NaBH4+2H2O→4R-CH2OH+NaBO2). The recovered reducing power in fermentation resulted in 99.3% recovery of the hydrogen yield and 64.6% recovery of peak production rate. Metabolite production and carbon conversion after detoxification significantly increased to 63.7mM and 81.9%, respectively. PMID:26342346

  14. Sodium borohydride removes aldehyde inhibitors for enhancing biohydrogen fermentation.

    Science.gov (United States)

    Lin, Richen; Cheng, Jun; Ding, Lingkan; Song, Wenlu; Zhou, Junhu; Cen, Kefa

    2015-12-01

    To enhance biohydrogen production from glucose and xylose in the presence of aldehyde inhibitors, reducing agent (i.e., sodium borohydride) was in situ added for effective detoxification. The detoxification efficiencies of furfural (96.7%) and 5-hydroxymethylfurfural (5-HMF, 91.7%) with 30mM NaBH4 were much higher than those of vanillin (77.3%) and syringaldehyde (69.3%). Biohydrogen fermentation was completely inhibited without detoxification, probably because of the consumption of nicotinamide adenine dinucleotide (NADH) by inhibitors reduction (R-CHO+2NADH→R-CH2OH+2NAD(+)). Addition of 30mM NaBH4 provided the reducing power necessary for inhibitors reduction (4R-CHO+NaBH4+2H2O→4R-CH2OH+NaBO2). The recovered reducing power in fermentation resulted in 99.3% recovery of the hydrogen yield and 64.6% recovery of peak production rate. Metabolite production and carbon conversion after detoxification significantly increased to 63.7mM and 81.9%, respectively.

  15. Uncatalyzed Condensation Reactions between Aromatic Aldehydes and Thiobarbituric Acid in Water

    Institute of Scientific and Technical Information of China (English)

    Bing Qin YANG; Jun LU; Min TIAN

    2003-01-01

    A series of 5-arylidene thiobarbituric acids were prepared from aromatic aldehydes and thiobarbituric acid in water without catalyst conditions in good yields. The structures were characterized by elemental analysis, IR and 1H NMR spectra.

  16. ARA-aldehyde and ABA-trans-diol in apple fruits

    Energy Technology Data Exchange (ETDEWEB)

    Rock, C.D.; Zeevaart, J.A.D. (Michigan State Univ., East Lansing (USA))

    1989-04-01

    We have isolated ABA-aldehyde and ABA-t-diol from postharvest apple fruits, cv. Granny Smith and confirmed their structure by GC-MS. These putative ABA biosynthetic precursors incorporate {sup 18}O to a similar degree as ABA during 48 hours under {sup 18}O{sub 2} atmospheres. The presence of significant amounts of ABA-aldehyde can explain the unique {sup 18}O labeling pattern of ABA in this tissue, where a majority of ABA molecules containing {sup 18}O is labeled in the 1{prime}-hydroxyl group and not in the side chain carboxyl group, the primary site of incorporation for stressed leaves. Exchange of the carbonyl oxygen of ABA-aldehyde with water would decrease {sup 18}O enrichment in the side chain. Results of {sup 18}O{sub 2} experiments and feeding studies using hexadeutero-ABA-aldehyde will be presented and the biosynthetic relationship of these compounds discussed.

  17. Ambient Ionic Liquids Used in the Reduction ofAldehydes and Ketones

    Institute of Scientific and Technical Information of China (English)

    Dan Qian XU; Shu Ping LUO; Bao You LIU; Zhen Yuan XU; Yin Chu SHEN

    2004-01-01

    The sodium borohydride reduction of aldehydes and ketones to corresponding alcohols has been accomplished via the use of ionic liquids. The alcohols are easily obtained with excellent yields and the ionic liquid BMImBF4 could be reused.

  18. Carbon-Carbon Bond Formation and Hydrogen Production in the Ketonization of Aldehydes.

    Science.gov (United States)

    Orozco, Lina M; Renz, Michael; Corma, Avelino

    2016-09-01

    Aldehydes possess relatively high chemical energy, which is the driving force for disproportionation reactions such as Cannizzaro and Tishchenko reactions. Generally, this energy is wasted if aldehydes are transformed into carboxylic acids with a sacrificial oxidant. Here, we describe a cascade reaction in which the surplus energy of the transformation is liberated as molecular hydrogen for the oxidation of heptanal to heptanoic acid by water, and the carboxylic acid is transformed into potentially industrially relevant symmetrical ketones by ketonic decarboxylation. The cascade reaction is catalyzed by monoclinic zirconium oxide (m-ZrO2 ). The reaction mechanism has been studied through cross-coupling experiments between different aldehydes and acids, and the final symmetrical ketones are formed by a reaction pathway that involves the previously formed carboxylic acids. Isotopic studies indicate that the carboxylic acid can be formed by a hydride shift from the adsorbed aldehyde on the metal oxide surface in the absence of noble metals. PMID:27539722

  19. Tetrabutylammonium fluoride promoted regiospecific reactions of trimethylsilyl-o-carborane with aldehydes

    International Nuclear Information System (INIS)

    Trimethylsilyl-o-carborane serves as o-carborane carbanion upon fluoride ion promoted reaction with carbonyl compounds. Thus, in the presence of tetrabutylammonium fluoride, trimethylsilyl-o-carborane undergoes facile, unprecedented, carbodesilylation with aromatic and aliphatic aldehydes. (author)

  20. Study on physico-chemical properties of dialdehyde yam starch with different aldehyde group contents

    International Nuclear Information System (INIS)

    Dialdehyde yam starches (DASs) are prepared and characterized. Compared with native starch, viscosity average molecular weight of DASs decreases, and the extent of degradation depends on content of the aldehyde groups. Fourier transform infrared (FT-IR) spectra confirm that the characteristic peak for C=O group at 1732 cm-1 is enhanced with the increasing of content of the aldehyde groups. Scanning electron microscopy (SEM) micrographs show that the surface of starch granules becomes wrinkled. X-ray diffraction (XRD) patterns clearly indicate that their crystallinity decreases with the increasing content of the aldehyde groups before they become amorphous at higher oxidation states. The experimental results of thermogravimetric analysis (TGA) show that DASs have poor stability as compared to native starch. With the increase in content of the aldehyde groups, the thermal stability of DAS declines gradually. According to the results of differential scanning calorimetry (DSC), gelatinization temperature (To and Tp) of DASs are increased, whereas the gelatinization enthalpy decreased.

  1. Organocatalytic enantioselective Michael addition reactions of fluoromalonates with α,β-unsaturated aldehydes

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A new organocatalytic enantioselective Michael addition of α-fluoromalonate to enals has been developed.The process is efficiently catalyzed by readily available chiral diphenylpyrolinol TES ether under mild reaction conditions to afford versatile highly enantioenriched fluorinated aldehydes.

  2. A Direct Transformation of Aryl Aldehydes to Benzyl Iodides Via Reductive Iodination

    Energy Technology Data Exchange (ETDEWEB)

    Ruso, Jayaraman Sembian; Rajendiran, Nagappan; Kumaran, Rajendran Senthil [Univ. of Madras, Chennai (India)

    2014-02-15

    A facile transformation of aryl aldehydes to benzyl iodides through one-pot reductive iodination is reported. This protocol displays remarkable functional group tolerance and the title compound was obtained in good to excellent yield.

  3. Oxidation of Group 8 transition-Metal Hydrides and Ionic Hydrogenation of Ketones and Aldehydes

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Kjell-Tore

    1996-08-01

    Transition-metal hydrides have received considerable attention during the last decades because of their unusual reactivity and their potential as homogeneous catalysts for hydrogenation and other reactions of organic substrates. An important class of catalytic processes where transition-metal hydrides are involved is the homogeneous hydrogenation of alkenes, alkynes, ketones, aldehydes, arenes and nitro compounds. This thesis studies the oxidation of Group 8 transition-metal hydrides and the ionic hydrogenation of ketones and aldehydes.

  4. Parallel Kinetic Resolution of Racemic Aldehydes by Use of Asymmetric Horner-Wadsworth-Emmons Reactions

    DEFF Research Database (Denmark)

    Pedersen, Torben Møller; Jensen, Jakob Feldthusen; Humble, Rikke Eva;

    2000-01-01

    A racemic aldehyde can undergo parallel kinetic resolution (PKR) by simultaneous reaction with two different chiral phosphonates, differing either in the structure of the chiral auxiliary or in the structure of the phosphoryl group (i.e., one (E)- and one (Z)-selective reagent). This strategy all...... allows conversion of a racemic aldehyde to two different, synthetically useful chiral products with essentially doubled material throughput and similar or improved selectivities as compared to conventional kinetic resolution....

  5. Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

    OpenAIRE

    Mikko Passiniemi; Koskinen, Ari M P

    2013-01-01

    Since its introduction to the synthetic community in 1984, Garner’s aldehyde has gained substantial attention as a chiral intermediate for the synthesis of numerous amino alcohol derivatives. This review presents some of the most successful carbon chain elongation reactions, namely carbonyl alkylations and olefinations. The literature is reviewed with particular attention on understanding how to avoid the deleterious epimerization of the existing stereocenter in Garner’s aldehyde.

  6. Formation of Aldehyde and Ketone Compounds during Production and Storage of Milk Powder

    OpenAIRE

    Weijun Wang; Lanwei Zhang; Yanhua Li

    2012-01-01

    Certain aldehyde and ketone compounds can be used as indicators, at a molecular level, of the oxidized flavor of milk powder instead of sensory evaluation. This study investigated the formation of aldehyde and ketone compounds as affected by the heat-related processing and storage of milk powder. The compounds were extracted by solid phase microextraction fiber and determined using gas chromatography-mass spectrometry. In the results, higher contents of hexanal, 2-heptanone, octanal and 3-oct...

  7. Chromatographic Methods for the Analyses of 2-Halofatty Aldehydes and Chlorohydrin Species of Lysophosphatidylcholine

    OpenAIRE

    Albert, Carolyn J; Anbukumar, Dhanalakshmi S.; Messner, Maria C.; Ford, David A.

    2008-01-01

    Plasmalogens are targeted by hypohalous acids resulting in the production of 2-chlorofatty aldehydes, 2-bromofatty aldehydes and chlorohydrin species of lysophosphatidylcholine. These novel lipids have required the development of techniques for their purification and quantification. Thin layer chromatography, high performance liquid chromatography and gas chromatography of these lipids and their derivatives have provided a battery of tools for their analyses. These lipids have been quantified...

  8. Flavour release of aldehydes and diacetyl in oil/water systems

    DEFF Research Database (Denmark)

    Haahr, Anne-Mette; Bredie, W. L. P.; Stahnke, Louise Heller;

    2000-01-01

    The concentration- and time-dependent release of three C-6-aldehydes, six C-9-aldehydes and diacetyl was studied in model systems. The systems were water, rapeseed oil and oil-in-water emulsions. Dynamic headspace sampling was used to collect the volatile compounds. In the concentration...... compounds was dependent on the chain length, the degree of unsaturation as well as the characteristics of the model system. (C) 2000 Elsevier Science Ltd. All rights reserved....

  9. An Improved Protocol for the Aldehyde Olefination Reaction Using (bmim ( as Reaction Medium

    Directory of Open Access Journals (Sweden)

    Vivek Srivastava

    2013-01-01

    Full Text Available [Ru(CODCl2]/CuCl2·2H2O/LiCl catalytic system works efficiently in ionic liquid media for aldehyde olefination reaction. It offers good yield and selectivity with the added advantage of 5 times recyclability for [Ru(CODCl2] /CuCl2·2H2O/LiCl catalytic system. We also successfully reduced the reaction time from 12 hours to 9 hours for the aldehyde olefination reaction.

  10. Accurate determination of aldehydes in amine catalysts or amines by 2,4-dinitrophenylhydrazine derivatization.

    Science.gov (United States)

    Barman, Bhajendra N

    2014-01-31

    Carbonyl compounds, specifically aldehydes, present in amine catalysts or amines are determined by reversed-phase liquid chromatography using ultraviolet detection of their corresponding 2,4-dinitrophenylhydrazones. The primary focus has been to establish optimum conditions for determining aldehydes accurately because these add exposure concerns when the amine catalysts are used to manufacture polyurethane products. Concentrations of aldehydes determined by this method are found to vary with the pH of the aqueous amine solution and the derivatization time, the latter being problematic when the derivatization reaction proceeds slowly and not to completion in neutral and basic media. Accurate determination of aldehydes in amines through derivatization can be carried out at an effective solution pH of about 2 and with derivatization time of 20min. Hydrochloric acid has been used for neutralization of an amine. For complete derivatization, it is essential to protonate all nitrogen atoms in the amine. An approach for the determination of an adequate amount of acid needed for complete derivatization has been described. Several 0.2M buffer solutions varying in pH from 4 to 8 have also been used to make amine solutions for carrying out derivatization of aldehydes. These solutions have effective pHs of 10 or higher and provide much lower aldehyde concentrations compared to their true values. Mechanisms for the formation of 2,4-dinitrophenylhydrazones in both acidic and basic media are discussed. PMID:24411140

  11. Effect of selected aldehydes on the growth and fermentation of ethanologenic Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Zaldivar, J.; Ingram, L.O. [Univ. of Florida, Gainesville (United States). Dept. of Microbiology and Cell Science; Martinez, A. [Univ. of Florida, Gainesville (United States). Dept. of Microbiology and Cell Science]|[Univ. Nacional Autonoma de Mexico (Mexico). Inst. de Biotecnologia

    1999-10-05

    Bioethanol production from lignocellulosic raw-materials requires the hydrolysis of carbohydrate polymers into a fermentable syrup. During the hydrolysis of hemicellulose with dilute acid, a variety of toxic compounds are produced such as soluble aromatic aldehydes from lignin and furfural from pentose destruction. In this study, the authors have investigated the toxicity of representative aldehydes (furfural, 5-hydroxymethlyfurfural, 4-hydroxybenzaldehyde, syringaldehyde, and vanillin) as inhibitors of growth and ethanol production by ethanologenic derivatives of Escherichia coli B (strains K011 and LY01). Aromatic aldyhydes were at least twice as toxic as furfural of 5-hydroxymethylfurfural on a weight basis. The toxicities of all aldehydes (and ethanol) except furfural were additive when tested in binary combinations. In all cases, combinations with furfural were unexpectedly toxic. Although the potency of these aldehydes was directly related to hydrophobicity indicating a hydrophobic site of action, none caused sufficient membrane damage to allow the leakage of intracellular magnesium even when present at sixfold the concentrations required for growth inhibition. Of the aldehydes tested, only furfural strongly inhibited ethanol production in vitro. A comparison with published results for other microorganisms indicates that LY01 is equivalent or more resistant than other biocatalysts to the aldehydes examined in this study.

  12. [Fatty aldehydes of the plasmalogenic form of phosphatidylethanolamine in the vertebrate brain].

    Science.gov (United States)

    Kruglova, E E

    1979-01-01

    Studies have been made on the composition of fatty aldehydes of plasmalogen form of ethanolamine phospholipid in the brain of 28 fish species (13 cartilaginous and 15 teleost species, exhibiting different level of organization of the nervous system, marine and freshwater, dwelling in different habitats), as well as in the brain of other vertebrates. It was found that in all primitive species of cartilaginous fish high degree of unsaturation of fatty aldehydes is observed; in higher species the degree of unsaturation is much lower. The highest degree of unsaturation of fatty aldehydes was demonstrated for abyssal species of cartilaginous and teleost fishes. In warm-water species which dwell in the upper layers, unlike all other fishes investigated, almost all fatty aldehydes are saturated. The ratio of unsaturated and saturated fatty aldehydes in fish brain depends on the entity of phylogenetic and ecological factors. Studies on other vertebrates show that in warm-blooded animals saturated fatty aldehydes predominate, whereas in cold-blooded-unsaturated ones are more abundant. PMID:314210

  13. Release and Formation of Oxidation-Related Aldehydes during Wine Oxidation.

    Science.gov (United States)

    Bueno, Mónica; Carrascón, Vanesa; Ferreira, Vicente

    2016-01-27

    Twenty-four Spanish wines were subjected to five consecutive cycles of air saturation at 25 °C. Free and bound forms of carbonyls were measured in the initial samples and after each saturation. Nonoxidized commercial wines contain important and sensory relevant amounts of oxidation-related carbonyls under the form of odorless bound forms. Models relating the contents in total aldehydes to the wine chemical composition suggest that fermentation can be a major origin for Strecker aldehydes: methional, phenylacetaldehyde, isobutyraldehyde, 2-methylbutanal, and isovaleraldehyde. Bound forms are further cleaved, releasing free aldehydes during the first steps of wine oxidation, as a consequence of equilibrium shifts caused by the depletion of SO2. At low levels of free SO2, de novo formation and aldehyde degradation are both observed. The relative importance of these phenomena depends on both the aldehyde and the wine. Models relating aldehyde formation rates to wine chemical composition suggest that amino acids are in most cases the most important precursors for de novo formation.

  14. Molecular cloning of gluconobacter oxydans DSM 2003 xylitol dehydrogenase gene

    OpenAIRE

    Sadeghi, H. Mir Mohammad; Ahmadi, R; Aghaabdollahian, S.; Mofid, M.R.; Ghaemi, Y.; Abedi, D

    2011-01-01

    Due to the widespread applications of xylitol dehydrogenase, an enzyme used for the production of xylitol, the present study was designed for the cloning of xylitol dehydrogenase gene from Glcunobacter oxydans DSM 2003. After extraction of genomic DNA from this bacterium, xylitol dehydrogenase gene was replicated using polymerase chain reaction (PCR). The amplified product was entered into pTZ57R cloning vector by T/A cloning method and transformation was performed by heat shocking of the E. ...

  15. Health-Beneficial Phenolic Aldehyde in Antigonon leptopus Tea

    Directory of Open Access Journals (Sweden)

    Vanisree Mulabagal

    2011-01-01

    Full Text Available Tea prepared from the aerial parts of Antigonon leptopus is used as a remedy for cold and pain relief in many countries. In this study, A. leptopus tea, prepared from the dried aerial parts, was evaluated for lipid peroxidation (LPO and cyclooxygenase (COX-1 and COX-2 enzyme inhibitory activities. The tea as a dried extract inhibited LPO, COX-1 and COX-2 enzymes by 78%, 38% and 89%, respectively, at 100 g/mL. Bioassay-guided fractionation of the extract yielded a selective COX-2 enzyme inhibitory phenolic aldehyde, 2,3,4-trihydroxy benzaldehyde. Also, it showed LPO inhibitory activity by 68.3% at 6.25 g/mL. Therefore, we have studied other hydroxy benzaldehydes and their methoxy analogs for LPO, COX-1 and COX-2 enzymes inhibitory activities and found that compound 1 gave the highest COX-2 enzyme inhibitory activity as indicated by a 50% inhibitory concentration (IC50 at 9.7 g/mL. The analogs showed only marginal LPO activity at 6.25 g/mL. The hydroxy analogs 6, 7 and 9 showed 55%, 61% and 43% of COX-2 inhibition at 100 g/mL. However, hydroxy benzaldehydes 3 and 12 showed selective COX-1 inhibition while compounds 4 and 10 gave little or no COX-2 enzyme inhibition at 100 g/mL. At the same concentration, compounds 14, 21 and 22 inhibited COX-1 by 83, 85 and 70%, respectively. Similarly, compounds 18, 19 and 23 inhibited COX-2 by 68%, 72% and 70%, at 100 g/mL. This is the first report on the isolation of compound 1 from A. leptopus tea with selective COX-2 enzyme and LPO inhibitory activities.

  16. Novel mutation in Sjogren-Larsson syndrome is associated with divergent neurologic phenotypes.

    Science.gov (United States)

    Davis, Kathleen; Holden, Kenton R; S'Aulis, Dana; Amador, Claudia; Matheus, M Gisele; Rizzo, William B

    2013-10-01

    Sjögren-Larsson syndrome is an inherited disorder of lipid metabolism caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase, which results in accumulation of fatty aldehydes and alcohols and is characterized by ichthyosis, intellectual disability, and spastic diplegia/quadriplegia. The authors describe 2 unrelated Honduran patients who carried the same novel homozygous nonsense mutation (c.1309A>T, p.K437X) and ALDH3A2 DNA haplotype, but widely differed in disease severity. One patient exhibited spastic quadriplegia with unusual neuroregression, whereas the other patient had the usual static form of spastic diplegia with neurodevelopmental disabilities. Biochemical analyses showed a similar profound deficiency of fatty aldehyde dehydrogenase activity and impaired fatty alcohol metabolism in both patients' cultured fibroblasts. These results indicate that variation in the neurologic phenotype of Sjögren-Larsson syndrome is not strictly determined by the ALDH3A2 mutation or the biochemical defect as expressed in cultured fibroblasts, but by unidentified epigenetic/environmental factors, gene modifiers, or other mechanisms.

  17. Physiological and Growth Responses of Tomato Progenies Harboring the Betaine Alhyde Dehydrogenase Gene to Salt Stress

    Institute of Scientific and Technical Information of China (English)

    Shu-Feng Zhou; Xian-Yang Chen; Xing-Ning Xue; Xin-Guo Zhang; Yin-Xin Li

    2007-01-01

    The responses of five transgenlc tomato (Lycoperslcon esculentum Mill) lines containing the betaine aldehyde dehydrogenase (BADH) gene to salt stress were evaluated. Proline, betaine (N, N, N-trimethylglycine, hereafter betaine), chlorophyll and ion contents, BADH activity, electrolyte leakage (EL), and some growth parameters of the plants under 1.0% and 1.5% NaCl treatments were examined. The transgenic tomatoes had enhanced BADH activity and betaine content, compared to the wild type under stress conditions. Salt stress reduced chlorophyll contents to a higher extent in the wild type than in the transgenic plants. The wild type exhibited significantly higher proline content than the transgenic plants at 0.9% and 1.3% NaCl. Cell membrane of the wild type was severely damaged as determined by higher EL under salinity stress. K+ and Ca2+ contents of all tested lines decreased under salt stress,but the transgenic plants showed a significantly higher accumulation of K+ and Ca2+ than the wild type. In contrast,the wild type had significantly higher Cl- and Na+ contents than the transgenic plants under salt stress. Although yield reduction among various lines varied, the wild type had the highest yield reduction. Fruit quality of the transgenic plants was better in comparison with the wild type as shown by a low ratio of blossom end rot fruits.The results show that the transgenic plants have improved salt tolerance over the wild type.

  18. Molecular genetic analysis of human alcohol dehydrogenase

    OpenAIRE

    Duester, G; Wesley Hatfield, G.; Smith, M.

    1985-01-01

    Human alcohol dehydrogenase (ADH) consists of a complex group of isozymes encoded by at least five non-identical genes, two of which have previously been shown through enzymatic analysis to possess polymorphic variants. Using a cDNA probe the ADH2gene encoding the β subunit of human ADH was mapped to human chromosome 4. The cDNA probe for ADH2 was also used to detect a restriction fragment length polymorphism present in human populations. This polymorphism may help establish whether certain A...

  19. Molecular determinants of the cofactor specificity of ribitol dehydrogenase, a short-chain dehydrogenase/reductase

    DEFF Research Database (Denmark)

    Moon, Hee-Jung; Tiwari, Manish Kumar; Singh, Ranjitha;

    2012-01-01

    Ribitol dehydrogenase from Zymomonas mobilis (ZmRDH) catalyzes the conversion of ribitol to d-ribulose and concomitantly reduces NAD(P)(+) to NAD(P)H. A systematic approach involving an initial sequence alignment-based residue screening, followed by a homology model-based screening and site...

  20. NAD(H recycling activity of an engineered bifunctional enzyme galactose dehydrogenase/lactate dehydrogenase

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available A chimeric bifunctional enzyme composing of galactose dehydrogenase (galDH; from Pseudomonas fluorescens and lactate dehydrogenase (LDH; from Bacillus stearothermophilus was successfully constructed. The chimeric galDH/LDH possessed dual characteristics of both galactose dehydrogenase and lactate dehydrogenase activities while exhibiting hexameric rearrangement with a molecular weight of approximately 400 kDa. In vitro observations showed that the chimeric enzyme was able to recycle NAD with a continuous production of lactate without any externally added NADH. Two fold higher recycling rate (0.3 mM/h than that of the native enzyme was observed at pH values above 8.5. Proximity effects became especially pronounced during the recycling assay when diffusion hindrance was induced by polyethylene glycol. All these findings open up a high feasibility to apply the NAD(H recycling system for metabolic engineering purposes e.g. as a model to gain a better understanding on the molecular proximity process and as the routes for synthesizing of numerous high-value-added compounds.

  1. TMPRSS4 induces cancer stem cell-like properties in lung cancer cells and correlates with ALDH expression in NSCLC patients.

    Science.gov (United States)

    de Aberasturi, Arrate L; Redrado, Miriam; Villalba, Maria; Larzabal, Leyre; Pajares, Maria J; Garcia, Javier; Evans, Stephanie R; Garcia-Ros, David; Bodegas, Maria Elena; Lopez, Lissett; Montuenga, Luis; Calvo, Alfonso

    2016-01-28

    Metastasis involves a series of changes in cancer cells that promote their escape from the primary tumor and colonization to a new organ. This process is related to the transition from an epithelial to a mesenchymal phenotype (EMT). Recently, some authors have shown that migratory cells with an EMT phenotype share properties of cancer stem cells (CSCs), which allow them to form a new tumor mass. The type II transmembrane serine protease TMPRSS4 is highly expressed in some solid tumors, promotes metastasis and confers EMT features to cancer cells. We hypothesized that TMPRSS4 could also provide CSC properties. Overexpression of TMPRSS4 reduces E-cadherin and induces N-cadherin and vimentin in A549 lung cancer cells, supporting an EMT phenotype. These changes are accompanied by enhanced migration, invasion and tumorigenicity in vivo. TMPRSS4 expression was highly increased in a panel of lung cancer cells cultured as tumorspheres (a typical assay to enrich for CSCs). H358 and H441 cells with knocked-down TMPRSS4 levels were significantly less able to form primary and secondary tumorspheres than control cells. Moreover, they showed a lower proportion of ALDH+ cells (examined by FACS analysis) and lower expression of some CSC markers than controls. A549 cells overexpressing TMPRSS4 conferred the opposite phenotype and were also more sensitive to the CSC-targeted drug salinomycin than control cells, but were more resistant to regular chemotherapeutic drugs (cisplatin, gemcitabine and 5-fluorouracil). Analysis of 70 NSCLC samples from patients revealed a very significant correlation between TMPRSS4 expression and CSC markers ALDH (p = 0.0018) and OCT4 (p = 0.0004), suggesting that TMPRSS4 is associated with a CSC phenotype in patients' tumors. These results show that TMPRSS4, in addition to inducing EMT, can also promote CSC features in lung cancer; therefore, CSC-targeting drugs could be an appropriate treatment for TMPRSS4+ tumors. PMID:26546046

  2. Biomarker screening of oral cancer cell lines revealed sub-populations of CD133-, CD44-, CD24- and ALDH1- positive cancer stem cells

    Directory of Open Access Journals (Sweden)

    Kendall K

    2013-05-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC ranks sixth worldwide for cancer-related mortality. For the past several decades the mainstay of treatment for HNSCC has been surgery and external beam radiation, although more recent trials combining chemotherapy and radiation have demonstrated improvements. However, cancer recurrence and treatment failures continue to occur in a significant percentage of patients. Recent advances in tumor biology have led to the discovery that many cancers, including HNSCC, may contain subpopulations of cells with stem cell-like properties that may explain relapse and recurrence. The objective of this study was to screen existing oral cancer cell lines for biomarkers specific for cells with stem cell-like properties. RNA was isolated for RT-PCR screening using primers for specific mRNA of the biomarkers: CD44, CD24, CD133, NANOG, Nestin, ALDH1, and ABCG2 in CAL27, SCC25 and SCC15 cells. This analysis revealed that some oral cancer cell lines (CAL27 and SCC25 may contain small subpopulations of adhesion- and contact-independent cells (AiDC that also express tumor stem cell markers, including CD44, CD133, and CD24. In addition, CAL27 cells also expressed the intracellular tumor stem cell markers, ALDH1 and ABCG2. Isolation and culture of the adhesion- and contact-independent cells from CAL27 and SCC25 populations revealed differential proliferation rates and more robust inhibition by the MEK inhibitor PD98059, as well as the chemotherapeutic agents Cisplatin and Paclitaxel, within the AiDC CAL27 cells. At least one oral cancer cell line (CAL27 contained subpopulations of cells that express specific biomarkers associated with tumor stem cells which were morphologically and phenotypically distinct from other cells within this cell line.

  3. DNA polymorphism and risk of esophageal squamous cell carcinoma in a population of North Xinjiang,China

    Institute of Scientific and Technical Information of China (English)

    Ilyar; Sheyhidin

    2010-01-01

    AIM:To investigate the role of metabolic enzyme and DNA repair genes in susceptibility of esophageal squamous cell carcinoma(ESCC). METHODS:A case-control study was designed with 454 samples from 128 ESCC patients and 326 gender, age and ethnicity-matched control subjects.Genotypes of 69 single nucleotide polymorphisms(SNPs)of metabolic enzyme(aldehyde dehydrogenase-2,ALDH2; alcohol dehydrogenase-1 B,ADHB1;Cytochrome P450 2A6,CYP2A6)and DNA repair capacity genes(excision repair cross complementing group 1,E...

  4. Microenvironmental characteristics important for personal exposures to aldehydes in Sacramento, CA, and Milwaukee, WI

    Science.gov (United States)

    Raymer, J. H.; Akland, G.; Johnson, T. R.; Long, T.; Michael, L.; Cauble, L.; McCombs, M.

    Oxygenated additives in gasoline are designed to decrease the ozone-forming hydrocarbons and total air toxics, yet they can increase the emissions of aldehydes and thus increase human exposure to these toxic compounds. This paper describes a study conducted to characterize targeted aldehydes in microenvironments in Sacramento, CA, and Milwaukee, WI, and to improve our understanding of the impact of the urban environment on human exposure to air toxics. Data were obtained from microenvironmental concentration measurements, integrated, 24-h personal measurements, indoor and outdoor pollutant monitors at the participants' residences, from ambient pollutant monitors at fixed-site locations in each city, and from real-time diaries and questionnaires completed by the technicians and participants. As part of this study, a model to predict personal exposures based on individual time/activity data was developed for comparison to measured concentrations. Predicted concentrations were generally within 25% of the measured concentrations. The microenvironments that people encounter daily provide for widely varying exposures to aldehydes. The activities that occur in those microenvironments can modulate the aldehyde concentrations dramatically, especially for environments such as "indoor at home." By considering personal activity, location (microenvironment), duration in the microenvironment, and a knowledge of the general concentrations of aldehydes in the various microenvironments, a simple model can do a reasonably good job of predicting the time-averaged personal exposures to aldehydes, even in the absence of monitoring data. Although concentrations of aldehydes measured indoors at the participants' homes tracked well with personal exposure, there were instances where personal exposures and indoor concentrations differed significantly. Key to the ability to predict exposure based on time/activity data is the quality and completeness of the microenvironmental

  5. Identification and characterization of an antennae-specific aldehyde oxidase from the navel orangeworm.

    Directory of Open Access Journals (Sweden)

    Young-Moo Choo

    Full Text Available Antennae-specific odorant-degrading enzymes (ODEs are postulated to inactivate odorant molecules after they convey their signal. Different classes of insect ODEs are specific to esters, alcohols, and aldehydes--the major functional groups of female-produced, hydrophobic sex pheromones from moth species. Esterases that rapidly inactive acetate and other esters have been well-studied, but less is known about aldehyde oxidases (AOXs. Here we report cloning of an aldehyde oxidase, AtraAOX2, from the antennae of the navel orangeworm (NOW, Amyelois transitella, and the first activity characterization of a recombinant insect AOX. AtraAOX2 gene spans 3,813 bp and encodes a protein with 1,270 amino acid residues. AtraAOX2 cDNA was expressed in baculovirus-infected insect Sf21 cells as a ≈280 kDa homodimer with 140 kDa subunits. Recombinant AtraAOX2 degraded Z11Z13-16Ald and plant volatile aldehydes as substrates. However, as expected for aldehyde oxidases, recombinant AtraAOX2 did not show specificity for Z11Z13-16Ald, the main constituent of the sex pheromone, but showed high activity for plant volatile aldehydes. Our data suggest AtraAOX2 might be involved in degradation of a diversity of aldehydes including sex pheromones, plant-derived semiochemicals, and chemical cues for oviposition sites. Additionally, AtraAOX2 could protect the insect's olfactory system from xenobiotics, including pesticides that might reach the sensillar lymph surrounding the olfactory receptor neurons.

  6. Transcriptional Regulation of Pyruvate Dehydrogenase Kinase

    Directory of Open Access Journals (Sweden)

    Ji Yun Jeong

    2012-10-01

    Full Text Available The pyruvate dehydrogenase complex (PDC activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK isoenzymes. Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally regulated still remains unclear. Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway. Several nuclear hormone receptors activated due to fasting or increased fat supply, including peroxisome proliferator-activated receptors, glucocorticoid receptors, estrogen-related receptors, and thyroid hormone receptors, also participate in the up-regulation of PDK2 and PDK4; however, the endogenous ligands that bind those nuclear receptors have not been identified. It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners. In this review, we discuss several factors involved in the expressional regulation of PDK2 and PDK4, and introduce current studies aimed at providing a better understanding of the molecular mechanisms that underlie the development of metabolic diseases such as diabetes.

  7. Transcriptional regulation of pyruvate dehydrogenase kinase.

    Science.gov (United States)

    Jeong, Ji Yun; Jeoung, Nam Ho; Park, Keun-Gyu; Lee, In-Kyu

    2012-10-01

    The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK) isoenzymes. Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally regulated still remains unclear. Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway. Several nuclear hormone receptors activated due to fasting or increased fat supply, including peroxisome proliferator-activated receptors, glucocorticoid receptors, estrogen-related receptors, and thyroid hormone receptors, also participate in the up-regulation of PDK2 and PDK4; however, the endogenous ligands that bind those nuclear receptors have not been identified. It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners. In this review, we discuss several factors involved in the expressional regulation of PDK2 and PDK4, and introduce current studies aimed at providing a better understanding of the molecular mechanisms that underlie the development of metabolic diseases such as diabetes. PMID:23130316

  8. Isobutyraldehyde production from Escherichia coli by removing aldehyde reductase activity

    Directory of Open Access Journals (Sweden)

    Rodriguez Gabriel M

    2012-06-01

    Full Text Available Abstract Background Increasing global demand and reliance on petroleum-derived chemicals will necessitate alternative sources for chemical feedstocks. Currently, 99% of chemical feedstocks are derived from petroleum and natural gas. Renewable methods for producing important chemical feedstocks largely remain unaddressed. Synthetic biology enables the renewable production of various chemicals from microorganisms by constructing unique metabolic pathways. Here, we engineer Escherichia coli for the production of isobutyraldehyde, which can be readily converted to various hydrocarbons currently derived from petroleum such as isobutyric acid, acetal, oxime and imine using existing chemical catalysis. Isobutyraldehyde can be readily stripped from cultures during production, which reduces toxic effects of isobutyraldehyde. Results We adopted the isobutanol pathway previously constructed in E. coli, neglecting the last step in the pathway where isobutyraldehyde is converted to isobutanol. However, this strain still overwhelmingly produced isobutanol (1.5 g/L/OD600 (isobutanol vs 0.14 g/L/OD600 (isobutyraldehyde. Next, we deleted yqhD which encodes a broad-substrate range aldehyde reductase known to be active toward isobutyraldehyde. This strain produced isobutanol and isobutyraldehyde at a near 1:1 ratio, indicating further native isobutyraldehyde reductase (IBR activity in E. coli. To further eliminate isobutanol formation, we set out to identify and remove the remaining IBRs from the E. coli genome. We identified 7 annotated genes coding for IBRs that could be active toward isobutyraldehyde: adhP, eutG, yiaY, yjgB, betA, fucO, eutE. Individual deletions of the genes yielded only marginal improvements. Therefore, we sequentially deleted all seven of the genes and assessed production. The combined deletions greatly increased isobutyraldehyde production (1.5 g/L/OD600 and decreased isobutanol production (0.4 g/L/OD600. By assessing production by

  9. Studies on the structure and function of pyruvate dehydrogenase complexes

    NARCIS (Netherlands)

    Abreu, de R.A.

    1978-01-01

    The aim of the present investigation was to obtain more information of the structure and function of the pyruvate dehydrogenase complexes from Azotobacter vinelandii and Escherichia coli.In chapter 2 a survey is given of the recent literature on pyruvate dehydrogenase complexes.In chapter 3 results

  10. Quantification of aldehydes emissions from alternative and renewable aviation fuels using a gas turbine engine

    Science.gov (United States)

    Li, Hu; Altaher, Mohamed A.; Wilson, Chris W.; Blakey, Simon; Chung, Winson; Rye, Lucas

    2014-02-01

    In this research three renewable aviation fuel blends including two HEFA (Hydrotreated Ester and Fatty Acid) blends and one FAE (Fatty Acids Ethyl Ester) blend with conventional Jet A-1 along with a GTL (Gas To Liquid) fuel have been tested for their aldehydes emissions on a small gas turbine engine. Three strong ozone formation precursors: formaldehyde, acetaldehyde and acrolein were measured in the exhaust at different operational modes and compared to neat Jet A-1. The aim is to assess the impact of renewable and alternative aviation fuels on aldehydes emissions from aircraft gas turbine engines so as to provide informed knowledge for the future deployment of new fuels in aviation. The results show that formaldehyde was a major aldehyde species emitted with a fraction of around 60% of total measured aldehydes emissions for all fuels. Acrolein was the second major emitted aldehyde species with a fraction of ˜30%. Acetaldehyde emissions were very low for all the fuels and below the detention limit of the instrument. The formaldehyde emissions at cold idle were up to two to threefold higher than that at full power. The fractions of formaldehyde were 6-10% and 20% of total hydrocarbon emissions in ppm at idle and full power respectively and doubled on a g kg-1-fuel basis.

  11. Nitrite promotes protein carbonylation and Strecker aldehyde formation in experimental fermented sausages: are both events connected?

    Science.gov (United States)

    Villaverde, A; Ventanas, J; Estévez, M

    2014-12-01

    The role played by curing agents (nitrite, ascorbate) on protein oxidation and Strecker aldehyde formation is studied. To fulfill this objective, increasing concentrations of nitrite (0, 75 and 150ppm) and ascorbate (0, 250 and 500ppm) were added to sausages subjected to a 54day drying process. The concurrence of intense proteolysis, protein carbonylation and formation of Strecker aldehydes during processing of sausages suggests that α-aminoadipic semialdehyde (AAS) and γ-glutamic semialdehyde (GGS) may be implicated in the formation of Strecker aldehydes. The fact that nitrite (150ppm, ingoing amount) significantly promoted the formation of protein carbonyls at early stages of processing and the subsequent formation of Strecker aldehydes provides strength to this hypothesis. Ascorbate (125 and 250ppm) controlled the overall extent of protein carbonylation in sausages without declining the formation of Strecker aldehydes. These results may contribute to understanding the chemistry fundamentals of the positive influence of nitrite on the flavor and overall acceptability of cured muscle foods.

  12. Toxicity of polyunsaturated aldehydes of diatoms to Indo-Pacific bioindicator organism Echinometra mathaei.

    Science.gov (United States)

    Sartori, Davide; Gaion, Andrea

    2016-01-01

    Although it is well known suitability of early developmental stages of sea urchin as recommended model for pollutant toxicity testing, little is known about the sensitivity of Indo-Pacific species Echinometra mathaei to polyunsaturated aldehydes. In this study, the effect of three short chain aldehydes, 2,4-decadienal (DD), 2,4-octadienal (OD) and 2,4-heptadienal (HD), normally found in many diatoms, such as Skeletonema costatum, Skeletonema marinoi and Thalassiosira rotula, was evaluated on larval development of E. mathaei embryos. Aldehydes affected larval development in a dose-dependent manner, in particular HD>OD>DD; the results of this study highlighted the higher sensitivity of this species toward aldehydes compared with data registered for other sea urchin species. In comparison with studies reported in the literature, contrasting results were observed during our tests; therefore, an increasing toxic effect was registered with decreasing the chain length of aldehydes. This work could provide new insights in the development of new toxicological assays toward most sensitive species. PMID:25945412

  13. INFLUENCE OF SELECTED PHARMACEUTICALS ON ACTIVATED SLUDGE DEHYDROGENASE ACTIVITY

    Directory of Open Access Journals (Sweden)

    Agnieszka Tomska

    2016-06-01

    The aim of this work was to evaluate the effect of selected antibiotics - sulfanilamide and erythromycin on activated sludge dehydrogenase activity with use of trifenyltetrazolinum chloride (TTC test. Dehydrogenases activity is an indicator of biochemical activity of microorganisms present in activated sludge or the ability to degrade organic compounds in waste water. TTC test is particularly useful for the regularity of the course of treatment, in which the presence of inhibitors of biochemical reactions and toxic compounds are present. It was observed that the dehydrogenase activity decreases with the increase of a antibiotics concentration. The lowest value of the dehydrogenase activity equal to 32.4 μmol TF / gMLSS obtained at sulfanilamide concentration 150mg / l. For this sample, an inhibition of dehydrogenase activity was 31%.

  14. Enantiocomplementary Yarrowia lipolytica Oxidoreductases: Alcohol Dehydrogenase 2 and Short Chain Dehydrogenase/Reductase

    Directory of Open Access Journals (Sweden)

    Margit Winkler

    2013-08-01

    Full Text Available Enzymes of the non-conventional yeast Yarrowia lipolytica seem to be tailor-made for the conversion of lipophilic substrates. Herein, we cloned and overexpressed the Zn-dependent alcohol dehydrogenase ADH2 from Yarrowia lipolytica in Escherichia coli. The purified enzyme was characterized in vitro. The substrate scope for YlADH2 mediated oxidation and reduction was investigated spectrophotometrically and the enzyme showed a broader substrate range than its homolog from Saccharomyces cerevisiae. A preference for secondary compared to primary alcohols in oxidation direction was observed for YlADH2. 2-Octanone was investigated in reduction mode in detail. Remarkably, YlADH2 displays perfect (S-selectivity and together with a highly (R-selective short chain dehydrogenase/ reductase from Yarrowia lipolytica it is possible to access both enantiomers of 2-octanol in >99% ee with Yarrowia lipolytica oxidoreductases.

  15. Stability of immobilized yeast alcohol dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Ooshima, H.; Genko, Y.; Harano, Y.

    1981-12-01

    The effects of substrate on stabilities of native (NA) and three kinds of immobilized yeast alcohol dehydrogenase (IMA), namely PGA (the carrier; porous glass), SEA (agarose gel) prepared covalently, and AMA (anion-exchange resin) prepared ionically, were studied. The following results were obtained. 1) The deactivations of NA and IMA free from the substrate or in the presence of ethanol obey the first-order kinetics, whereas, in the presence of butyraldehyde, their deactivation behaviors are explained on the basis of coexistence of two components of YADHs, namely the labile E1 and the comparatively stable E2, with different first-order deactivation constants. (2) A few attempts for stabilization of IMA were carried out from the viewpoint of the effects of crosslinkages among the subunits of YADH for PGA and the multibonding between the carrier and enzyme for SEA. The former is effective for the stabilization, whereas the latter is not. (Refs. 19).

  16. Interactions between heparinoids and alcohol dehydrogenase.

    Science.gov (United States)

    Paulíková, H; Valusová, E; Antalík, M

    1997-07-01

    The interaction between polysulfated polysaecharides (low-molecular-weight heparin LMWH, dextran sulfate DS and pentosan sulfate PS) and yeast alcohol dehydrogenase (YADH) was investigated. The fluorescence and UV spectra of YADH after adding the tested polysaccharides have confirmed the interaction between the enzyme and these compounds. Kinetic studies have shown that LMWH, DS and PS are inhibitors of YADH (mixed type with respect to NAD). The most potent inhibitor is PS (ID50=37.5 ng/ml, Ki=0.6 muM). The inhibition effect depends on the ionic strength (the inhibition decreased by about 50% in the presence of 100 mM Na2SO4) and pH value (the inhibition decreased at pH>7). The results indicate that the inhibition effect of these polyanions is caused by their electrostatic interactions with the NAD-binding region of YADH.

  17. Optimization of adsorptive immobilization of alcohol dehydrogenases.

    Science.gov (United States)

    Trivedi, Archana; Heinemann, Matthias; Spiess, Antje C; Daussmann, Thomas; Büchs, Jochen

    2005-04-01

    In this work, a systematic examination of various parameters of adsorptive immobilization of alcohol dehydrogenases (ADHs) on solid support is performed and the impact of these parameters on immobilization efficiency is studied. Depending on the source of the enzymes, these parameters differently influence the immobilization efficiency, expressed in terms of residual activity and protein loading. Residual activity of 79% was achieved with ADH from bakers' yeast (YADH) after optimizing the immobilization parameters. A step-wise drying process has been found to be more effective than one-step drying. A hypothesis of deactivation through bubble nucleation during drying of the enzyme/glass bead suspension at low drying pressure (300% residual activity was found after drying. Hyperactivation of the enzyme is probably caused by structural changes in the enzyme molecule during the drying process. ADH from Thermoanaerobacter species (ADH T) is found to be stable under drying conditions (>15 kPa) in contrast to LBADH and YADH.

  18. Untangling the glutamate dehydrogenase allosteric nightmare.

    Science.gov (United States)

    Smith, Thomas J; Stanley, Charles A

    2008-11-01

    Glutamate dehydrogenase (GDH) is found in all living organisms, but only animal GDH is regulated by a large repertoire of metabolites. More than 50 years of research to better understand the mechanism and role of this allosteric network has been frustrated by its sheer complexity. However, recent studies have begun to tease out how and why this complex behavior evolved. Much of GDH regulation probably occurs by controlling a complex ballet of motion necessary for catalytic turnover and has evolved concomitantly with a long antenna-like feature of the structure of the enzyme. Ciliates, the 'missing link' in GDH evolution, might have created the antenna to accommodate changing organelle functions and was refined in humans to, at least in part, link amino acid catabolism with insulin secretion.

  19. Oxidative desulfurization of diesel with TBHP/isobutyl aldehyde/air oxidation system

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Wei; Wang, Chengyong; Lin, Peng; Lu, Xiaoping [Institute of Sonochemical Engineering, Nanjing University of Technology, Nanjing 210009, Jiangsu (China)

    2011-01-15

    Oxidative desulfurization of hydrogenation diesel (40 mL) was studied using air as oxidant, tert-butyl hydroperoxide (TBHP) as radical initiator at ambient pressure and moderate temperature in the presence of isobutyl aldehyde. TBHP could accelerate the production of carbonyl radical and its peroxidation. When the molar fraction of TBHP was 5 mmol, the conversion of DBT could reach 96.1% in the present of 20 mmol isobutyl aldehyde and air, which was more than that of 85.5% without initiator. The air was an effective oxidant and acetonitrile was an optimal solvent in this process. The sulfur content of the hydrogenation diesel could be reduced from 403 to 13 ppm (96.8% removed) under the synergistic effect of air, TBHP and isobutyl aldehyde. (author)

  20. Evolution of volatile aldehydes in Iberian ham matured under different processing conditions.

    Science.gov (United States)

    Martín, L; Timón, M L; Petrón, M J; Ventanas, J; Antequera, T

    2000-04-01

    To evaluate the influence of the Iberian ham processing conditions in the evolution of volatile aldehydes, 35 hams were processed in two plants following different conditions of relative humidity and temperature. For this, free fatty acids, peroxide values and volatile aldehydes were quantified in the hams. The highest increases in free fatty acids were noted during the drying stage in both processing plants. The drying period also revealed the greatest increase in peroxide values, where the highest values were in those hams processed at higher temperatures. The temperature during post-salting and drying had a marked influence on the formation of volatile aldehydes, being responsible for the differences in volatile compounds of matured hams.

  1. Catalytic production of methyl acrylates by gold-mediated cross coupling of unsaturated aldehydes with methanol

    Science.gov (United States)

    Karakalos, Stavros; Zugic, Branko; Stowers, Kara J.; Biener, Monika M.; Biener, Juergen; Friend, Cynthia M.; Madix, Robert J.

    2016-10-01

    Modern methods of esterification, one of the most important reactions in organic synthesis, are reaching their limits, as far as waste and expense are concerned. Novel chemical approaches to ester formation are therefore of importance. Here we report a simple procedure free of caustic reagents or byproducts for the facile direct oxidative methyl esterification of aldehydes over nanoporous Au catalysts. Complementary model studies on single crystal gold surfaces establish the fundamental reactions involved. We find that methanol more readily reacts with adsorbed active oxygen than do the aldehydes, but that once the aldehydes do react, they form strongly-bound acrylates that block reactive sites and decrease the yields of acrylic esters under steady flow conditions at 420 K. Significant improvements in yield can be achieved by operating at higher temperatures, which render the site-blocking acrylates unstable.

  2. Microwave Irradiated Reactions of N-Phenacylpyridinium Chloride with Aromatic Aldehydes and Ketones

    Institute of Scientific and Technical Information of China (English)

    Ping WU; Xi Mei CAI; Rong YAO; Chao Guo YAN

    2006-01-01

    In the system of ammonium acetate and acetic acid and under microwave irradiation,N-phenacylpyridinium chloride 1 reacted with chalcone 2 to give 2,4,6-triarylpyrididnes 3a-g in high yields. 3a-g can also be prepared from one-pot reaction of 1 with aromatic aldehydes 4 and substituted acetophenones 5. Under the same conditions 1 can also react with pyridinecar boxaldehyde 6a-c and acetophenone to yield bipyridine derivatives 7a-c. 1 reacted with aromatic aldehyde and cyclohexanone 6 to yield 2,4-diaryltetrahydroquinolines 8a-d. At last 1 reacted with aromatic aldehydes to give 2,4,6-triarylpyrimidine 9a-i. The structure of the products was characterized with 1H NMR and IR and mass spectroscopy.

  3. Organic acids and aldehydes in rainwater in a northwest region of Spain

    Energy Technology Data Exchange (ETDEWEB)

    Pena, R.M.; Garcia, S.; Herrero, C. [Universidad de Santiago de Compostela, Lugo (Spain). Departamento de Quimica Analitica, Nutricion y Bromatologia

    2002-11-01

    During a 1 year period, measurements of carboxylic acids and aldehydes were carried out in rainwater samples collected at nine different sites in NW Spain surrounding a thermal power plant in order to determine concentration levels and sources. In addition, certain major ions (Cl{sup -}, NO{sub 3}{sup -}, SO{sub 4}{sup 2-}, Na{sup +}, NH{sub 4}{sup +}, K{sup +}, Mg{sup 2+}, Ca{sup 2+}) were also determined. Aldehyde and carboxylic acid concentration patterns and their effects on rainwater composition concerning temporal, seasonal and spatial variations were evaluated. Among carboxylic acids, formic and acetic were predominant (VWA 7.0 and 8.3 {mu}M), while formaldehyde and acroleine were the dominant aldehydes (VWA 0.42 and 1.25 {mu}M). Carboxylic acids were estimated to account for 27.5% of the total free acidity (TFA), whereas sulphuric and nitric acid accounted for 46.2% and 26.2%, respectively. Oxalic acid was demonstrated to be an important contributing compound to the acidification in rainwater representing 7.1% of the TFA. The concentration of aldehydes and carboxylic acids, which originated mainly from biogenic emissions in the area studied, was strongly dependent on the season of the year (growing and non-growing). The ratios of formic to acetic acids are considerably different in the two seasons suggesting that there exist distinct sources in both growing and non-growing seasons. Principal component analysis was applied in order to elucidate the sources of aldehydes and organic acids in rainwater. The prevalence of natural vegetative origins for both of these compounds versus anthropogenic emissions was demonstrated and the importance of the oxidation of aldehydes as a relevant source of organic acids was also established. (author)

  4. Synthesis of Discodermolide Subunits by S(E)2' Addition of Nonracemic Allenylstannanes to Aldehydes.

    Science.gov (United States)

    Marshall, James A.; Lu, Zhi-Hui; Johns, Brian A.

    1998-02-01

    Three subunits, 15, 29, and 34, of the immunosuppressant discodermolide were prepared starting from (S)-3-[(tert-butyldimethylsilyl)oxy]-2-methylpropanal ((S)-1) and the enantioenriched allenylstannanes (P)-2a, (P)-2b, and (P)-31. The route to 15 involved BF(3)-promoted addition of stannane (P)-2a to aldehyde (S)-1 which afforded the syn,syn-homopropargylic alcohol adduct 3 in 97% yield. The derived p-methoxybenzylidene acetal 5 was treated with Red-Al to effect cleavage of the pivalate and reduction of the double bond leading to the (E)-allylic alcohol 6. Sharpless epoxidation and subsequent addition of Me(2)CuCNLi(2) yielded the syn,syn,syn,anti stereopentad, diol 8. Protection of the secondary alcohol and oxidation of the primary gave aldehyde 12, which was treated with the alpha-bromo allylsilane 13 and CrCl(2), followed by NaH to effect elimination to the diene 15. A similar sequence was employed to prepare aldehyde 29. In this case aldehyde (S)-1 was converted to the anti,syn-homopropargylic alcohol 20 by treatment with the allenyl indium reagent formed in situ from allenylstannane (P)-2b and InBr(3). Epoxy alcohol 24, prepared from alcohol 20 by the above-described sequence, was reduced with Red-Al to afford diol 25. Protection of the secondary alcohol and oxidation of the primary completed the synthesis of 29. The anti,syn-homopropargylic alcohol 32 was obtained through addition of the allenic indium reagent, from allenylstannane (P)-31, to aldehyde (S)-1. Protection of the derived diol 33 as the p-methoxybenzylidene acetal afforded the third subunit, acetylene 34. Addition of the lithio derivative of 34 to aldehyde 29 gave alcohol 35 with the carbinyl stereochemistry needed for C7 of discodermolide as the major product.

  5. Nephelauxetic and hypersensitive nature of neodymium(III) complexes with α-pyridyl-thiosemicarbazide and its furfural-2-aldehyde and thiophene-2-aldehyde derivatives

    International Nuclear Information System (INIS)

    A new series of octahedral Nd(III) complexes with recently synthesised α-pyridylthiosemicarbazide (C6H8N4S or 'PT'), N-(α-pyridyl)furfural-2-aldehyde-thiosemicarbazone (C11H10N4SO or 'PFT') and N-(α-pyridyl)thiophene-2-aldehyde-thiosemicarbazone (C11H10N4S2 or 'PTT'), have been isolated and characterised on the basis of their elemental analysis, magnetic and reflectance and ir spectral data revealing 'PT' as bidentate (pyridinic-N and thioketo-S) and 'PFT' and 'PTT' as tetradentate with pyridinic-N, thioketo-S, imine-N and furfuryl-O/thiophenyl-S as donor sites. Isolation and characterisation of Nd(III) complexes with 'PT', 'PFT' and 'PTT' and their nephelauxetic and hypersensitive nature are studied in order to evaluate the stereochemistry of the ligands around Nd(III) ion. (author). 12 refs., 2 tables

  6. Effects of the biodiesel blend fuel on aldehyde emissions from diesel engine exhaust

    Science.gov (United States)

    Peng, Chiung-Yu; Yang, Hsi-Hsien; Lan, Cheng-Hang; Chien, Shu-Mei

    Interest in use of biodiesel fuels derived from vegetable oils or animal fats as alternative fuels for petroleum-based diesels has increased due to biodiesels having similar properties of those of diesels, and characteristics of renewability, biodegradability and potential beneficial effects on exhaust emissions. Generally, exhaust emissions of regulated pollutants are widely studied and the results favor biodiesels on CO, HC and particulate emissions; however, limited and inconsistent data are showed for unregulated pollutants, such as carbonyl compounds, which are also important indicators for evaluating available vehicle fuels. For better understanding biodiesel, this study examines the effects of the biodiesel blend fuel on aldehyde chemical emissions from diesel engine exhausts in comparison with those from the diesel fuel. Test engines (Mitsubishi 4M40-2AT1) with four cylinders, a total displacement of 2.84 L, maximum horsepower of 80.9 kW at 3700 rpm, and maximum torque of 217.6 N m at 2000 rpm, were mounted and operated on a Schenck DyNAS 335 dynamometer. Exhaust emission tests were performed several times for each fuel under the US transient cycle protocol from mileages of 0-80,000 km with an interval of 20,000 km, and two additional measurements were carried out at 40,000 and 80,000 km after maintenance, respectively. Aldehyde samples were collected from diluted exhaust by using a constant volume sampling system. Samples were extracted and analyzed by the HPLC/UV system. Dominant aldehydes of both fuels' exhausts are formaldehyde and acetaldehyde. These compounds together account for over 75% of total aldehyde emissions. Total aldehyde emissions for B20 (20% waste cooking oil biodiesel and 80% diesel) and diesel fuels are in the ranges of 15.4-26.9 mg bhp-h -1 and 21.3-28.6 mg bhp-h -1, respectively. The effects of increasing mileages and maintenance practice on aldehyde emissions are insignificant for both fuels. B20 generates slightly less emission than

  7. The absence of aldehyde dehydrogenase 1 A1-positive cells in benign mammary stroma is associated with risk factors for breast cancer

    OpenAIRE

    Isfoss BL; Holmqvist B; Jernström H; Alm P; Olsson H.

    2016-01-01

    Björn Logi Isfoss,1–3 Bo Holmqvist,1,4 Helena Jernström,1 Per Alm,1 Håkan Olsson1,5 1Department of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, 2Department of Pathology, Skane University Hospital, Lund, Sweden; 3Department of Pathology, Telemark Hospital, Skien, Norway; 4ImaGene-iT AB, Medicon Village, 5Division of Cancer Epidemiology, Department of Clinical Sciences, Lund University, Lund, Sweden Abstract: In this study,...

  8. Caracterización de polimorfismos de los genes ADH2, ADH3, ALDH2 y CYP2E1 y su relación con el alcoholismo en una población colombiana

    Directory of Open Access Journals (Sweden)

    Claudia Méndez

    2015-12-01

    Full Text Available Objective:Identify and characterize polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 in a Colombian population residing in the city of Bogotá and determine its possible relationship to the alcoholism.Methods:ADH2, ADH3, ALDH2, and CYP2E1 genotypes a population of 148 individuals with non-problematic alcohol and 65 individuals with alcoholism were determined with TaqMan probes and PCR-RFLP. DNA was obtained from peripheral blood white cells.Results:Significant difference was found in family history of alcoholism and use of other psychoactive substances to compare alcoholics with controls. When allelic frequencies for each category (gender were considered, frequency of A2 allele carriers in ADH2 was found higher in male patients than controls. In women, the relative frequency for c1 allele in CYP2E1 was lower in controls than alcoholics. The ALDH2 locus is monomorphic. No significant differences in allele distributions of the loci examined to compare two populations were observed, however when stratifying the same trend was found that these differences tended to be significant.Conclusions:This study allows us to conclude the positive association between family history of alcoholism and alcoholism suggesting that there is a favourable hereditary predisposition. Since substance dependence requires interaction of multiple genes, the combination of genotypes ADH2 * 2, CYP2E1 * 1 combined with genotype homozygous ALDH2 * 1 found in this study could be leading to the population to a potential risk to alcoholism. 

  9. On the role of long-chain aldehydes in the light reaction in Photobacterium phosphoreum enzyme preparations

    NARCIS (Netherlands)

    Terpstra, Willemke

    1960-01-01

    1. (1) Active luciferase-DPNH-oxidase preparations from Photobacterium phosphoreum generally contain some aldehyde-attacking enzyme, probably ADH. Under the experimental conditions applied this enzyme appears to attack decanal, but not palmital. 2. (2) The presence of long-chain aldehydes in the en

  10. Aldehyde-Selective Wacker-Type Oxidation of Unbiased Alkenes Enabled by a Nitrite Co-Catalyst

    KAUST Repository

    Wickens, Zachary K.

    2013-09-13

    Breaking the rules: Reversal of the high Markovnikov selectivity of Wacker-type oxidations was accomplished using a nitrite co-catalyst. Unbiased aliphatic alkenes can be oxidized with high yield and aldehyde selectivity, and several functional groups are tolerated. 18O-labeling experiments indicate that the aldehydic O atom is derived from the nitrite salt.

  11. Aldehyde Selective Wacker Oxidations of Phthalimide Protected Allylic Amines : A New Catalytic Route to beta(3)-Amino Acids

    NARCIS (Netherlands)

    Weiner, Barbara; Baeza Garcia, Alejandro; Jerphagnon, Thomas; Feringa, Ben L.

    2009-01-01

    A new method for the synthesis of B-3-amino acids is presented. Phthalimide protected allylic amines are oxidized under Wacker conditions selectively to aldehydes using PdCl2 and CuCl or Pd(MeCN)(2)Cl(NO2) and CuCl2 as complementary catalyst systems. The aldehydes are produced in excellent yields an

  12. Kinetic mechanism of an aldehyde reductase of Saccharomyces cerevisiae that relieves toxicity of furfural and 5-hydroxymethylfurfural

    Science.gov (United States)

    An effective means of relieving the toxicity of furan aldehydes, furfural (FFA) and 5-hydroxymethylfurfural (HMF), on fermenting organisms is essential for achieving efficient fermentation of lignocellulosic biomass to ethanol and other products. Ari1p, an aldehyde reductase from Saccharomyces cerev...

  13. Kinetics of forming aldehydes in frying oils and their distribution in French fries revealed by LC-MS-based chemometrics

    Science.gov (United States)

    Aldehydes are major secondary lipid oxidation products (LOPs) from heating vegetable oils and deep frying. The routes and reactions that generate aldehydes have been extensively investigated, but the sequences and kinetics of their formation in oils are poorly defined. In this study, a platform comb...

  14. Biospecific affinity chromatographic purification of octopine dehydrogenase from molluscs.

    Science.gov (United States)

    Mulcahy, P; Griffin, T; O'Carra, P

    1997-02-01

    The development of a biospecific affinity chromatographic method for the purification of octopine dehydrogenase from molluscs is described. The method utilizes immobilized NAD+ derivatives in conjunction with soluble specific substrates to promote binding. Using this method, octopine dehydrogenase has been purified to electrophoretic homogeneity in a single chromatographic step from three different marine invertebrate sources [the queen scallop, Chlamys opercularis (adductor muscle), the great scallop, Pecten maximus (adductor muscle), and the squid Loligo vulgaris (mantle muscle)]. However, the system is not applicable to the purification of octopine dehydrogenase from some other marine invertebrate sources investigated (the mussel Mytilus edulis and the topshell Monodonta lineata). PMID:9116492

  15. Rate constants for a mechanism including intermediates in the interconversion of ternary complexes by horse liver alcohol dehydrogenase

    International Nuclear Information System (INIS)

    Transient kinetic data for partial reactions of alcohol dehydrogenase and simulations of progress curves have led to estimates of rate constants for the following mechanism, at pH 8.0 and 25 degrees C: E in equilibrium E-NAD+ in equilibrium *E-NAD+ in equilibrium E-NAD(+)-RCH2OH in equilibrium E-NAD+-RCH2O- in equilibrium *E-NADH-RCHO in equilibrium E-NADH-RCHO in equilibrium E-NADH in equilibrium E. Previous results show that the E-NAD+ complex isomerizes with a forward rate constant of 620 s-1. The enzyme-NAD(+)-alcohol complex has a pK value of 7.2 and loses a proton rapidly (greater than 1000 s-1). The transient oxidation of ethanol is 2-fold faster in D2O, and proton inventory results suggest that the transition state has a charge of -0.3 on the substrate oxygen. Rate constants for hydride ion transfer in the forward or reverse reactions were similar for short-chain aliphatic substrates (400-600 s-1). A small deuterium isotope effect for transient oxidation of longer chain alcohols is apparently due to the isomerization of the E-NAD+ complex. The transient reduction of aliphatic aldehydes showed no primary deuterium isotope effect; thus, an isomerization of the E-NADH-aldehyde complex is postulated, as isomerization of the E-NADH complex was too fast to be detected. The estimated microscopic rate constants show that the observed transient reactions are controlled by multiple steps

  16. Modelling of the partial oxidation of {alpha}, {beta}-unsaturated aldehydes on Mo-V-oxides based catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Boehnke, H.; Petzoldt, J.C.; Stein, B.; Weimer, C.; Gaube, J.W. [Technische Univ. Darmstadt (Germany). Inst. fuer Chemische Technologie

    1998-12-31

    A kinetic model based on the Mars-van Krevelen mechanism that allows to describe the microkinetics of the heterogeneously catalysed partial oxidation of {alpha}, {beta}-unsaturated aldehydes is presented. This conversion is represented by a network, composed of the oxidation of the {alpha}, {beta}-unsaturated aldehyde towards the {alpha}, {beta}-unsaturated carboxylic acid and the consecutive oxidation of the acid as well as the parallel reaction of the aldehyde to products of deeper oxidation. The reaction steps of aldehyde respectively acid oxidation and catalyst reoxidation have been investigated separately in transient experiments. The combination of steady state and transient experiments has led to an improved understanding of the interaction of the catalyst with the aldehyde and the carboxylic acids as well as to a support of the kinetic model assumptions. (orig.)

  17. [Classification of alcohol metabolizing enzymes and polymorphisms--specificity in Japanese].

    Science.gov (United States)

    Harada, S

    2001-04-01

    Multiple forms and gene loci of human alcohol dehydrogenase (ADH EC: 1.2.1.3) and aldehyde dehydrogenase (ALDH, EC: 1.2.1.3) in the major pathway of alcohol metabolism have been found and characterized in the last two decades. With the coenzyme NAD, these enzymes catalyze the reversible conversion of organic alcohols to ketones or aldehydes, and aldehyde to acetic acid. The ADH genes are mapped to chromosome 4p21-25, but the ALDH genes are localized at different chromosomes. The cytochrome P450 2E1 (CYP2E1) gene, which is mapped to chromosome 10q24.3-qter contributes also the conversion of ethanol to acetaldehyde. Genetic polymorphisms have been reported in these alcohol metabolizing enzymes. The metabolisms of alcohol and acetaldehyde in liver and blood after drinking alcohol are thought to be influenced by the interactive action of these enzymes. Amongst the five major classes of the ADH subunits (alpha, beta, gamma, pi, chi, sigma), beta and gamma subunits show genetic polymorphisms. Recently a new nomenclature for ALDH genes has been recommend based on divergent evolution and chromosomal mapping. Two major isoforms designated as cytosolic ALDH1 and mitochondrial ALDH2 can be distinguished by their electrophoretic and kinetic properties as well as by their subcellular localization. Mitochondrial ALDH2 is a major enzyme in the oxidation of acetaldehyde derived from ethanol metabolism. The catalytic deficiency of ALDH2 isozyme is responsible for flushing and other vasomotor symptoms caused by higher acetaldehyde levels after alcohol intake. So far, frequencies of the two alleles of ALDH2 in Mongoloid have been reported in the different population groups. The catalytic deficiency of ALDH2 is caused by a structural point mutation at amino acid position 487, where a substitution of Glu to Lys resulting from a transition of G (C) to A (T) at 1510 nucleotide from the initiation codon has occurred. Individuals deficient in ALDH2 activity refrain from excessive drinking

  18. An Improved Protocol for the Pd-catalyzed α-Arylation of Aldehydes with Aryl Halides

    OpenAIRE

    Martín, Rubén; Buchwald, Stephen L.

    2008-01-01

    An improved protocol for the Pd-catalyzed α-arylation of aldehydes with aryl halides has been developed. The new catalytic system allows for the coupling of an array of substrates including challenging electron-rich aryl bromides and less reactive aryl chlorides. The utility of this method has been demonstrated in a new total synthesis of (±)-sporochnol.

  19. STUDY ON THE CARDANOL-ALDEHYDE CONDENSATION POLYMER CONTAINING BORON-NITROGEN COORDINATE BOND

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    Cardanol-aldehyde condensation polymer containing boron-nitrogen coordinate bond (CFBN) has been synthesized and characterized by IR, XPS, HPLC and DTA-TG. Its properties were also investigated. The results show that the coating film of CFBN has excellent physico-mechanical properties, good anticorrosive properties and stable at high temperature.

  20. Integrated quantification and identification of aldehydes and ketones in biological samples

    NARCIS (Netherlands)

    Siegel, David; Meinema, Anne C; Permentier, Hjalmar; Hopfgartner, Gérard; Bischoff, Rainer

    2014-01-01

    The identification of unknown compounds remains to be a bottleneck of mass spectrometry (MS)-based metabolomics screening experiments. Here, we present a novel approach which facilitates the identification and quantification of analytes containing aldehyde and ketone groups in biological samples by

  1. Phosphite Ligand Modified Supported Rhodium Catalyst for Hydroformylation of Internal Olefins to Linear Aldehydes

    Institute of Scientific and Technical Information of China (English)

    LI Xian-ming; DING Yun-jie; JIAO Gui-ping; LI Jing-wei; YAN Li; ZHU He-jun

    2009-01-01

    A phosphite ligand modified heterogeneous catalyst was developed for the hydroformylation of internal olefins to linear aldehydes, which showed a high activity and high regioselectivity and could be separated easily by filtration after reaction in an autoclave. Three nanoporous silica sieves were used to investigate the influence of pore structure and shape selective performance of support on the regioselectivity to the linear products.

  2. Reductive Amination of Aldehydes and Ketones with Primary Amines by Using Lithium Amidoborane as Reducing Reagent

    Institute of Scientific and Technical Information of China (English)

    徐维亮; 郑学丽; 吴国涛; 陈萍

    2012-01-01

    A variety of secondary amines were obtained in high isolated yields in the reductive amination of aldehydes and ketones by using lithium amidoborane as reducing agent. Compared to ammonia borane, lithium amidoborane has higher reducibility, and thus, exhibits faster reaction rate.

  3. Analysis of endogenous aldehydes in human urine by static headspace gas chromatography-mass spectrometry.

    Science.gov (United States)

    Serrano, María; Gallego, Mercedes; Silva, Manuel

    2016-03-11

    Endogenous aldehydes (EAs) generated during oxidative stress and cell processes are associated with many pathogenic and toxicogenic processes. The aim of this research was to develop a solvent-free and automated analytical method for the determination of EAs in human urine using a static headspace generator sampler coupled with gas chromatography-mass spectrometry (HS-GC-MS). Twelve significant EAs used as markers of different biochemical and physiological processes, namely short- and medium-chain alkanals, α,β-unsaturated aldehydes and dicarbonyl aldehydes have been selected as target analytes. Human urine samples (no dilution is required) were derivatized with O-2,3,4,5,6-pentafluorobenzylhydroxylamine in alkaline medium (hydrogen carbonate-carbonate buffer, pH 10.3). The HS-GC-MS method developed renders an efficient tool for the sensitive and precise determination of EAs in human urine with limits of detection from 1 to 15ng/L and relative standard deviations, (RSDs) from 6.0 to 7.9%. Average recoveries by enriching urine samples ranged between 92 and 95%. Aldehydes were readily determined at 0.005-50μg/L levels in human urine from healthy subjects, smokers and diabetic adults.

  4. Ambient concentrations of aldehydes in relation to Beijing Olympic air pollution control measures

    Science.gov (United States)

    Gong, J. C.; Zhu, T.; Hu, M.; Zhang, L. W.; Cheng, H.; Zhang, L.; Tong, J.; Zhang, J.

    2010-08-01

    Aldehydes are ubiquitous constituents of the atmosphere. Their concentrations are elevated in polluted urban atmospheres. The present study was carried out to characterize three aldehydes of most health concern (formaldehyde, acetaldehyde, and acrolein) in a central Beijing site in the summer and early fall of 2008 (from June to October). Measurements were made before, during, and after the Beijing Olympics to examine whether the air pollution control measures implemented to improve Beijing's air quality during the Olympics had any impact on concentrations of the three aldehydes. Average concentrations of formaldehyde, acetaldehyde and acrolein were 29.34 ± 15.12 μg/m3, 27.09 ± 15.74 μg/m3 and 2.32 ± 0.95 μg/m3, respectively, for the entire period of measurements, all being the highest among the levels measured in cities around the world in photochemical smog seasons. Among the three measured aldehydes, only acetaldehyde had a substantially reduced mean concentration during the Olympic air pollution control period compared to the pre-Olympic period. Formaldehyde and acrolein followed the changing pattern of temperature and were each significantly correlated with ozone (a secondary product of photochemical reactions). In contrast, acetaldehyde was significantly correlated with several pollutants emitted mainly from local emission sources (e.g., NO2, CO, and PM2.5). These findings suggest that local direct emissions had a larger impact on acetaldehyde than formaldehyde and acrolein.

  5. APPLICATION OF MULTISPECTRAL TECHNIQUES TO THE PRECISE IDENTIFICATION OF ALDEHYDES IN THE ENVIRONMENT

    Science.gov (United States)

    By using gas chromatography coupled with low- and high-resolution electron impact mass spectrometry, low- and high-resolution chemical ionization mass spectrometry, and Fourier transform infrared spectroscopy, eight straight-chain aldehydes were identified in a water sample taken...

  6. Pyridinium tribromide catalyzed condensation of indoles and aldehydes to form bisindolylalkanes

    Institute of Scientific and Technical Information of China (English)

    Qin Yang; Zheng Lan Yin; Ban Lai Ouyang; Yi Yuan Peng

    2011-01-01

    An efficient synthetic method for bis(indol-3-yl)alkane derivatives has been developed. In the presence of 5 mol% of pyridinium tribromide (PTB), the condensation of indoles and aldehydes proceeded smoothly under mild conditions, giving rise to the corresponding bis(indol-3-yl)alkanes in good to excellent yields.

  7. Inhibitory effects of Ruta graveolens L. extract on guinea pig liver aldehyde oxidase.

    Science.gov (United States)

    Pirouzpanah, Saieed; Saieed, Pirouzpanah; Rashidi, Mohammad Reza; Reza, Rashidi Mohammad; Delazar, Abbas; Abbas, Delazar; Razavieh, Seyyed-Vali; Seyyedvali, Razavieh; Hamidi, Aliasghar; Aliasghar, Hamidi

    2006-01-01

    Ruta graveolens L. is a flavonoid-containing medicinal plant with various biological properties. In the present study, the effects of R. graveolens extract on aldehyde oxidase, a molybdenum hydroxylase, are investigated. Aldehyde oxidase was partially purified from liver homogenates of mature male guinea pigs by heat treatment and ammonium sulphate precipitation. The total extract was obtained by macerating the aerial parts of R. graveolens in MeOH 70% and the effect of this extract on the enzyme activity was assayed using phenanthridine, vanillin and benzaldehyde as substrates. Quercetin and its glycoside form, rutin were isolated, purified and identified from the extract and their inhibitory effects on the enzyme were investigated. R. graveolens extract exhibited a high inhibition on aldehyde oxidase activity (89-96%) at 100 microg/ml which was comparable with 10 microM of menadione, a specific potent inhibitor of aldehyde oxidase. The IC50 values for the inhibitory effect of extract against the oxidation of benzaldehyde, vanillin and phenanthridine were 10.4, 10.1, 43.2 microg/ml, respectively. Both quercetin and rutin at 10 microM caused 70-96% and 27-52% inhibition on the enzyme activity, respectively. Quercetin was more potent inhibitor than rutin, but both flavonols exerted their inhibitory effects mostly in a linear mixed-type.

  8. Size-Selective Oxidation of Aldehydes with Zeolite Encapsulated Gold Nanoparticles

    DEFF Research Database (Denmark)

    Højholt, Karen Thrane; Laursen, Anders Bo; Kegnæs, Søren;

    2011-01-01

    Here, we report a synthesis and catalytic study of hybrid materials comprised of 1–3 nm sinter-stable Au nanoparticles in MFI-type zeolites. An optional post-treatment in aqua regia effectively remove Au from the external surfaces. The size-selective aerobic aldehyde oxidation verifies...

  9. Perfluoroalkanesulfonamide Organocatalysts for Asymmetric Conjugate Additions of Branched Aldehydes to Vinyl Sulfones

    Directory of Open Access Journals (Sweden)

    Kosuke Nakashima

    2013-11-01

    Full Text Available Asymmetric conjugate additions of branched aldehydes to vinyl sulfones promoted by sulfonamide organocatalyst 6 or 7 have been developed, allowing facile synthesis of the corresponding adducts with all-carbon quaternary stereocenters in excellent yields with up to 95% ee.

  10. Bifunctional Enantioselective Ligands of Chiral BINOL Derivatives for Asymmetric Addition of Alkynylzinc to Aldehydes

    Institute of Scientific and Technical Information of China (English)

    ZOU Xiao-Wei; ZHENG Li-Fei; WU Ling-Lin; ZONG Li-Li; CHENG Yi-Xiang

    2008-01-01

    Four analogous binaphthyl compounds (R)-3a-3d containing (R)-3,3'-bis(2-pyridyl) groups were synthesized by the conjugation of (R)-2,2'-dimethoxy-1,1'-binaphthyl-3,3'-diboronic acid [(R)-2] with 2-bromopyridine,2-bromo-5-methylpyridine, 2-chloro-4-fluoropyridine and 2-chloro-3-(trifluoromethyl)pyridine via Pd-catalyzed Suzuki reactions, respectively.The application of the four chiral ligands in combination with Et2Zn and Ti(Oi-Pr)4 to the asymmetric addition of phenylacetylene to various aldehydes has been studied.The results show that (R)-3a and (R)-3b are not good catalysts for the alkynylzinc addition to aldehydes, (R)-3d shows good enantioselectivity only for the alkynylzinc addition to aliphatic aldehydes, and (R)-3c exhibits excellent enantioselectivity for phenylethynylzinc addition to both aromatic and aliphatic aldehydes.All the four chiral ligands produced the opposite configuration of the propargylic alcohols to that of the chiral ligands.

  11. The Condensation of Aromatic Aldehydes with Acidic Methylene Compounds in Water

    Institute of Scientific and Technical Information of China (English)

    Da Qing SHI; Jing CHEN; Qi Ya ZHUANG; Xiang Shan WANG; Hong Wen HU

    2003-01-01

    The condensation of aromatic aldehydes with acidic methylene compounds such as malononitrile, methyl cyanoacetate, cyanoacetamide, 5,5-dimethyl-1,3-cyclohexanedione, bartbituric acid and 2-thiobarbituric acid proceeded very efficiently in water in the presence of triethylbenzylammonium chloride (TEBA) and the products were isolated simply by filtration.

  12. Kinetics of acid-catalyzed aldol condensation reactions of aliphatic aldehydes

    Science.gov (United States)

    Casale, Mia T.; Richman, Aviva R.; Elrod, Matthew J.; Garland, Rebecca M.; Beaver, Melinda R.; Tolbert, Margaret A.

    Field observations of atmospheric aerosols have established that organic compounds compose a large fraction of the atmospheric aerosol mass. However, the physical/chemical pathway by which organic compounds are incorporated into atmospheric aerosols remains unclear. The potential role of acid-catalyzed reactions of organic compounds on acidic aerosols has been explored as a possible chemical pathway for the incorporation of organic material into aerosols. In the present study, ultraviolet-visible (UV-vis) spectroscopy was used to monitor the kinetics of formation of the products of the acid-catalyzed aldol condensation reaction of a range of aliphatic aldehydes (C 2-C 8). The experiments were carried out at various sulfuric acid concentrations and a range of temperatures in order to estimate the rate constants of such reactions on sulfuric acid aerosols under tropospheric conditions. The rate constants were generally found to decrease as the chain length of the aliphatic aldehyde increased (except for acetaldehyde, which had an unusually small rate constant), increase as a function of sulfuric acid concentration as predicted by excess acidity theory, and showed normal Arrhenius behavior as a function of temperature. While the kinetic data are generally consistent with previous laboratory reports of aldehyde reactivity in various sulfuric acid media, the aldol condensation reactions involving aliphatic aldehydes do not appear fast enough to be responsible for significant transfer of organic material into atmospheric aerosols.

  13. Study on physico-chemical properties of dialdehyde yam starch with different aldehyde group contents

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liming, E-mail: zhanglmd@yahoo.com.cn [Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457 (China); Liu, Peng; Wang, Yugao [College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Gao, Wenyuan [Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457 (China)

    2011-01-10

    Dialdehyde yam starches (DASs) are prepared and characterized. Compared with native starch, viscosity average molecular weight of DASs decreases, and the extent of degradation depends on content of the aldehyde groups. Fourier transform infrared (FT-IR) spectra confirm that the characteristic peak for C=O group at 1732 cm{sup -1} is enhanced with the increasing of content of the aldehyde groups. Scanning electron microscopy (SEM) micrographs show that the surface of starch granules becomes wrinkled. X-ray diffraction (XRD) patterns clearly indicate that their crystallinity decreases with the increasing content of the aldehyde groups before they become amorphous at higher oxidation states. The experimental results of thermogravimetric analysis (TGA) show that DASs have poor stability as compared to native starch. With the increase in content of the aldehyde groups, the thermal stability of DAS declines gradually. According to the results of differential scanning calorimetry (DSC), gelatinization temperature (T{sub o} and T{sub p}) of DASs are increased, whereas the gelatinization enthalpy decreased.

  14. The acid free asymmetric intermolecular α-alkylation of aldehydes in fluorinated alcohols.

    Science.gov (United States)

    Xiao, Jian; Zhao, Kai; Loh, Teck-Peng

    2012-04-11

    The acid free asymmetric intermolecular α-alkylation of aldehydes with alcohols has been discovered using trifluoroethanol as solvent. This unprecedented system affords the enantioenriched functionalized primary alcohols (after NaBH(4) reduction) in high yields and good to excellent enantioselectivities with wide substrate scope in the absence of any acid additive.

  15. Fructose derived pyridyl alcohol ligands: synthesis and application in the asymmetric diethylzinc addition to aldehydes

    Institute of Scientific and Technical Information of China (English)

    ZHOU, Yong-Gui; DAI, Li-Xin; HOU, Xue-Long

    2000-01-01

    Easily available chiral ketones were employed for the synthesis of optically active pyridyl alcohols, which were applied in the asymmetric diethylzinc addition to aldehydes, up to 89.4%e.e. was obtained using D-fructose-derived pyridyl alcohol.

  16. Enantioselective Pinacol Coupling of Aromatic Aldehydes Induced by Chiral Titanium Complexes

    Institute of Scientific and Technical Information of China (English)

    Qing Fang CHENG; Xing You XU; Ming Yan WANG; Jun CHEN; Wei Xing MA; Xu Jie YANG

    2006-01-01

    Asymmetric pinacol coupling of aromatic aldehydes with TiCl4-Zn in the presence of enantiopure squaric acid amidoalcohols afforded 1, 2-diols in excellent yields with high dldiastereoselectivities and enantioselectivities in the range of 46-89% ee. Some factors influencing dl-diastereoselectivity and enantioselectivity were discussed.

  17. A new device for formaldehyde and total aldehydes real-time monitoring.

    Science.gov (United States)

    Sassine, Maria; Picquet-Varrault, Bénédicte; Perraudin, Emilie; Chiappini, Laura; Doussin, Jean François; George, Christian

    2014-01-01

    A new sensitive technique for the quantification of formaldehyde (HCHO) and total aldehydes has been developed in order to monitor these compounds, which are known to be involved in air quality issues and to have health impacts. Our approach is based on a colorimetric method where aldehydes are initially stripped from the air into a scrubbing solution by means of a turning coil sampler tube and then derivatised with 3-methylbenzothiazolinone-2-hydrazone in acid media (pH = -0.5). Hence, colourless aldehydes are transformed into blue dyes that are detected by UV-visible spectroscopy at 630 nm. Liquid core waveguide LCW Teflon® AF-2400 tube was used as innovative optical cells providing a HCHO detection limit of 4 pptv for 100 cm optical path with a time resolution of 15 min. This instrument showed good correlation with commonly used techniques for aldehydes analysis such as DNPH derivatisation chromatographic techniques with off-line and on-line samplers, and DOAS techniques (with deviation below 6%) for both indoor and outdoor conditions. This instrument is associated with simplicity and low cost, which is a prerequisite for indoor monitoring. PMID:23892614

  18. Fast determination of aldehyde preservatives by miniaturized capillary electrophoresis with amperometric detection.

    Science.gov (United States)

    Li, Ying; Chen, Fang; Ge, Jinyuan; Tong, Fanghong; Deng, Zhaoyue; Shen, Fengwu; Gu, Qianxia; Ye, Jiannong; Chu, Qingcui

    2014-02-01

    A novel miniaturized CE with amperometric detection (mini-CE-AD) method has been developed for fast determination of aliphatic aldehyde preservatives, namely formaldehyde and glyoxal, in commodities. After derivatization with an electroactive compound 2-thiobarbituric acid, these two nonelectroactive aldehydes were converted to electroactive adducts, therefore detectable by mini-CE-AD approach. Under the optimum conditions, two aldehydes can be well-separated with the coexisting interferents as well as their homologs (acetaldehyde and methyl-glyoxal), and the LODs (S/N = 3) were achieved at nanogram-per-milliliter level (1.64-2.80 ng/mL) based on the online enrichment method of transient moving chemical reaction boundary. The proposed method has been applied for the analyses of above aldehyde preservatives in different real commodity samples including skincare products, baby lotion, and toothpaste, and the average recoveries were in the range of 94-105%, which should find a wide range of analytical applications as an alternative to conventional and microchip CE approaches.

  19. A novel glutamate dehydrogenase from bovine brain: purification and characterization.

    Science.gov (United States)

    Lee, J; Kim, S W; Cho, S W

    1995-08-01

    A soluble form of novel glutamate dehydrogenase has been purified from bovine brain. The preparation was homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and composed of six identical subunits having a subunit size of 57,500 Da. The biochemical properties of glutamate dehydrogenase such as N-terminal amino acids sequences, kinetic parameters, amino acids analysis, and optimum pH were examined in both reductive amination of alpha-ketoglutarate and oxidative deamination of glutamate. N-terminal amino acid sequences of the bovine brain enzyme showed the significant differences in the first 5 amino acids compared to other glutamate dehydrogenases from various sources. These results indicate that glutamate dehydrogenase isolated from bovine brain is a novel polypeptide.

  20. Targeting isocitrate dehydrogenase (IDH) in cancer.

    Science.gov (United States)

    Fujii, Takeo; Khawaja, Muhammad Rizwan; DiNardo, Courtney D; Atkins, Johnique T; Janku, Filip

    2016-05-01

    Isocitrate dehydrogenase (IDH) is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma. The mutated IDH1 and IDH2 proteins have a gain-of-function, neomorphic activity, catalyzing the reduction of α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG) by NADPH. Cancer-associated IDH mutations block normal cellular differentiation and promote tumorigenesis via the abnormal production of the oncometabolite 2-HG. High levels of 2-HG have been shown to inhibit α-KG dependent dioxygenases, including histone and deoxyribonucleic acid (DNA) demethylases, which play a key role in regulating the epigenetic state of cells. Current targeted inhibitors of IDH1 (AG120, IDH305), IDH2 (AG221), and pan-IDH1/2 (AG881) selectively inhibit mutant IDH protein and induce cell differentiation in in vitro and in vivo models. Preliminary results from phase I clinical trials with IDH inhibitors in patients with advanced hematologic malignancies have demonstrated an objective response rate ranging from 31% to 40% with durable responses (>1 year) observed. Furthermore, the IDH inhibitors have demonstrated early signals of activity in solid tumors with IDH mutations, including cholangiocarcinomas and low grade gliomas. PMID:27355333

  1. Lactic dehydrogenase and cancer: an overview.

    Science.gov (United States)

    Gallo, Monica; Sapio, Luigi; Spina, Annamaria; Naviglio, Daniele; Calogero, Armando; Naviglio, Silvio

    2015-01-01

    Despite the intense scientific efforts made, there are still many tumors that are difficult to treat and the percentage of patient survival in the long-term is still too low. Thus, new approaches to the treatment of cancer are needed. Cancer is a highly heterogeneous and complex disease, whose development requires a reorganization of cell metabolism. Most tumor cells downregulate mitochondrial oxidative phosphorylation and increase the rate of glucose consumption and lactate release, independently of oxygen availability (Warburg effect). This metabolic rewiring is largely believed to favour tumor growth and survival, although the underlying molecular mechanisms are not completely understood. Importantly, the correlation between the aerobic glycolysis and cancer is widely regarded as a useful biochemical basis for the development of novel anticancer strategies. Among the enzymes involved in glycolysis, lactate dehydrogenase (LDH) is emerging as a very attractive target for possible pharmacological approaches in cancer therapy. This review addresses the state of the art and the perspectives concerning LDH both as a useful diagnostic marker and a relevant molecular target in cancer therapy and management.

  2. Role of aldehyde chemistry and NOx concentrations in secondary organic aerosol formation

    Directory of Open Access Journals (Sweden)

    P. O. Wennberg

    2010-04-01

    Full Text Available Aldehydes are an important class of products from atmospheric oxidation of hydrocarbons. Isoprene (2-methyl-1,3-butadiene, the most abundantly emitted atmospheric non-methane hydrocarbon, produces a significant amount of secondary organic aerosol (SOA via methacrolein (a C4-unsaturated aldehyde under urban high-NOx conditions. Previously, we have identified peroxy methacryloyl nitrate (MPAN as the important intermediate to isoprene and methacrolein SOA in this NOx regime. Here we show that as a result of this chemistry, NO2 enhances SOA formation from methacrolein and two other α, β-unsaturated aldehydes, specifically acrolein and crotonaldehyde, a NOx effect on SOA formation previously unrecognized. Oligoesters of dihydroxycarboxylic acids and hydroxynitrooxycarboxylic acids are observed to increase with increasing NO2/NO ratio, and previous characterizations are confirmed by both online and offline high-resolution mass spectrometry techniques. Molecular structure also determines the amount of SOA formation, as the SOA mass yields are the highest for aldehydes that are α, β-unsaturated and contain an additional methyl group on the α-carbon. Aerosol formation from 2-methyl-3-buten-2-ol (MBO232 is insignificant, even under high-NO2 conditions, as PAN (peroxy acyl nitrate, RC(OOONO2 formation is structurally unfavorable. At atmospherically relevant NO2/NO ratios, the SOA yields from isoprene high-NOxphotooxidation are 3 times greater than previously measured at lower NO2/NO ratios. At sufficiently high NO2 concentrations, in systems of α, β-unsaturated aldehydes, SOA formation from subsequent oxidation of products from acyl peroxyl radicals+NO2 can exceed that from RO2+HO2 reactions under the same inorganic seed conditions, making RO2+NO2 an important channel for SOA formation.

  3. Role of aldehyde chemistry and NOx concentrations in secondary organic aerosol formation

    Directory of Open Access Journals (Sweden)

    P. O. Wennberg

    2010-08-01

    Full Text Available Aldehydes are an important class of products from atmospheric oxidation of hydrocarbons. Isoprene (2-methyl-1,3-butadiene, the most abundantly emitted atmospheric non-methane hydrocarbon, produces a significant amount of secondary organic aerosol (SOA via methacrolein (a C4-unsaturated aldehyde under urban high-NOx conditions. Previously, we have identified peroxy methacryloyl nitrate (MPAN as the important intermediate to isoprene and methacrolein SOA in this NOx regime. Here we show that as a result of this chemistry, NO2 enhances SOA formation from methacrolein and two other α, β-unsaturated aldehydes, specifically acrolein and crotonaldehyde, a NOx effect on SOA formation previously unrecognized. Oligoesters of dihydroxycarboxylic acids and hydroxynitrooxycarboxylic acids are observed to increase with increasing NO2/NO ratio, and previous characterizations are confirmed by both online and offline high-resolution mass spectrometry techniques. Molecular structure also determines the amount of SOA formation, as the SOA mass yields are the highest for aldehydes that are α, β-unsaturated and contain an additional methyl group on the α-carbon. Aerosol formation from 2-methyl-3-buten-2-ol (MBO232 is insignificant, even under high-NO2 conditions, as PAN (peroxy acyl nitrate, RC(OOONO2 formation is structurally unfavorable. At atmospherically relevant NO2/NO ratios (3–8, the SOA yields from isoprene high-NOx photooxidation are 3 times greater than previously measured at lower NO2/NO ratios. At sufficiently high NO2 concentrations, in systems of α, β-unsaturated aldehydes, SOA formation from subsequent oxidation of products from acyl peroxyl radicals+NO2 can exceed that from RO2+HO2 reactions under the same inorganic seed conditions, making RO2+NO2 an important channel for SOA formation.

  4. COMPUTATIONAL STUDIES OF THE KINETIC ISOTOPE EFFECT INMETHYLAMINE DEHYDROGENASE

    OpenAIRE

    Kopec-Harding, Kamilla Rosa

    2012-01-01

    There is currently experimental evidence of hydrogen tunnelling in over 20 different enzymes include yeast alcohol dehydrogenase (YADH), morphinone reductase (MR) and methylamine dehydrogenase (MADH). Various models have been used to describe hydrogen tunnelling in enzymes including the static barrier model, the vibrationally enhanced ground state tunnelling model (VEGST) and the environmentally coupled tunnelling model (ECT). Despite some differences in these models, there is a general cons...

  5. Inhibitors of 17beta-hydroxysteroid dehydrogenase type 1.

    Science.gov (United States)

    Brozic, P; Lanisnik Risner, T; Gobec, S

    2008-01-01

    Carcinogenesis of hormone-related cancers involves hormone-stimulated cell proliferation, which increases the number of cell divisions and the opportunity for random genetic errors. In target tissues, steroid hormones are interconverted between their potent, high affinity forms for their respective receptors and their inactive, low affinity forms. One group of enzymes responsible for these interconversions are the hydroxysteroid dehydrogenases, which regulate ligand access to steroid receptors and thus act at a pre-receptor level. As part of this group, the 17beta-hydroxysteroid dehydrogenases catalyze either oxidation of hydroxyl groups or reduction of keto groups at steroid position C17. The thoroughly characterized 17beta-hydroxysteroid dehydrogenase type 1 activates the less active estrone to estradiol, a potent ligand for estrogen receptors. This isoform is expressed in gonads, where it affects circulating levels of estradiol, and in peripheral tissue, where it regulates ligand occupancy of estrogen receptors. Inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 are thus highly interesting potential therapeutic agents for the control of estrogen-dependent diseases such as endometriosis, as well as breast and ovarian cancers. Here, we present the review on the recent development of inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 published and patented since the previous review of 17beta-hydroxysteroid dehydrogenase inhibitors of Poirier (Curr. Med. Chem., 2003, 10, 453). These inhibitors are divided into two separate groups according to their chemical structures: steroidal and non-steroidal 17beta-hydroxysteroid dehydrogenase type 1 inhibitors. Their estrogenic/ proliferative activities and selectivities over other 17beta-hydroxysteroid dehydrogenases that are involved in local regulation of estrogen action (types 2, 7 and 12) are also presented. PMID:18220769

  6. Aromatic amine dehydrogenase, a second tryptophan tryptophylquinone enzyme.

    OpenAIRE

    Govindaraj, S; Eisenstein, E.; Jones, L. H.; Sanders-Loehr, J; Chistoserdov, A Y; Davidson, V L; Edwards, S. L.

    1994-01-01

    Aromatic amine dehydrogenase (AADH) catalyzes the oxidative deamination of aromatic amines including tyramine and dopamine. AADH is structurally similar to methylamine dehydrogenase (MADH) and possesses the same tryptophan tryptophylquinone (TTQ) prosthetic group. AADH exhibits an alpha 2 beta 2 structure with subunit molecular weights of 39,000 and 18,000 and with a quinone covalently attached to each beta subunit. Neither subunit cross-reacted immunologically with antibodies to the correspo...

  7. Dehydrogenase isoenzyme polymorphism in genus Prunus, subgenus Cerasus

    Directory of Open Access Journals (Sweden)

    Čolić Slavica

    2012-01-01

    Full Text Available Dehydrogenase polymorphism was studied in 36 sour cherry (Prunus cerasus L., sweet cherry (Prunus avuim L., mahaleb (Prunus mahaleb L., ground cherry (Prunus fruticosa Pall., duke cherry (Prunus gondounii Redh., Japanese flowering cherry (Prunus serrulata Lindl. and four iterspecific hybrids (standard cherry rootstocks ‘Gisela 5’, ‘Gisela 6’, ‘Max Ma’ and ‘Colt’. Inner bark of one-year-old shoots, in dormant stage, was used for enzyme extraction. Vertical PAGE was used for isoenzyme analysis: alcohol dehydrogenase (ADH, formate dehydrogenase (FDH, glutamate dehydrogenase (GDH, isocitrate dehydrogenaze (IDH, malate dehydrogenase (MDH, phosphogluconate dehydrogenase (PGD, and shikimate dehydrogenase (SDH. All studied systems were polymorphic at 10 loci: Adh -1 (3 genotypes and Adh-2 (5 genotypes, Fdh-1 (2 genotypes, Gdh-1 (3 genotypes, Idh-1 (4 genotypes i Idh -2 (5 genotypes, Mdh-1 (3 genotypes, Pgd-1 (4 genotypes, Sdh-1 (1 genotype i Sdh-2 (3 genotypes. Cluster analysis was used to construct dendrogram on which four groups of similar genotypes were separated. Obtained results indicate that studied enzyme systems can be used for determination of genus Prunus, subgenus Cerasus. Among studied enzyme systems ADH, IDH and SDH were the most polymorphic and most useful to identify genetic variability. Polymorphism of FDH and GDH in genus Prunus, subgenus Cerasus was described first time in this work. First results for dehydrogenase variability of Oblačinska indicate that polymorphism of loci Idh-2 and Sdh-2 can be useful for discrimination of different clones.

  8. Structural basis for cellobiose dehydrogenase action during oxidative cellulose degradation

    OpenAIRE

    Tan, Tien-Chye; Kracher, Daniel; Gandini, Rosaria; Sygmund, Christoph; Kittl, Roman; Haltrich, Dietmar; Hallberg, B Martin; Ludwig, Roland; Divne, Christina

    2015-01-01

    A new paradigm for cellulose depolymerization by fungi focuses on an oxidative mechanism involving cellobiose dehydrogenases (CDH) and copper-dependent lytic polysaccharide monooxygenases (LPMO); however, mechanistic studies have been hampered by the lack of structural information regarding CDH. CDH contains a haem-binding cytochrome (CYT) connected via a flexible linker to a flavin-dependent dehydrogenase (DH). Electrons are generated from cellobiose oxidation catalysed by DH and shuttled vi...

  9. In vitro inhibition of 10-formyltetrahydrofolate dehydrogenase activity by acetaldehyde

    OpenAIRE

    Mun, Ju-Ae; Doh, Eunjin; Min, Hyesun

    2008-01-01

    Alcoholism has been associated with folate deficiency in humans and laboratory animals. Previous study showed that ethanol feeding reduces the dehydrogenase and hydrolase activity of 10-formyltetrahydrofolate dehydrogenase (FDH) in rat liver. Hepatic ethanol metabolism generates acetaldehyde and acetate. The mechanisms by which ethanol and its metabolites produce toxicity within the liver cells are unknown. We purified FDH from rat liver and investigated the effect of ethanol, acetaldehyde an...

  10. The oxidation of yeast alcohol dehydrogenase-1 by hydrogen peroxide in vitro.

    Science.gov (United States)

    Men, Lijie; Wang, Yinsheng

    2007-01-01

    Yeast alcohol dehydrogenase (YADH) plays an important role in the conversion of alcohols to aldehydes or ketones. YADH-1 is a zinc-containing protein, and it accounts for the major part of ADH activity in growing baker's yeast. To gain insight into how oxidative modification of the enzyme affects its function, we exposed YADH-1 to hydrogen peroxide in vitro and assessed the oxidized protein by LC-MS/MS analysis of proteolytic cleavage products of the protein and by measurements of enzymatic activity, zinc release, and thiol/thiolate loss. The results illustrated that Cys43 and Cys153, which reside at the active site of the protein, could be selectively oxidized to cysteine sulfinic acid (Cys-SO2H) and cysteine sulfonic acid (Cys-SO3H). In addition, H2O2 induced the formation of three disulfide bonds: Cys43-Cys153 in the catalytic domain, Cys103-Cys111 in the noncatalytic zinc center, and Cys276-Cys277. Therefore, our results support the notion that the oxidation of cysteine residues in the zinc-binding domain of proteins can go beyond the formation of disulfide bond(s); the formation of Cys-SO2H and Cys-SO3H is also possible. Furthermore, most methionines could be oxidized to methionine sulfoxides. Quantitative measurement results revealed that, among all the cysteine residues, Cys43 was the most susceptible to H2O2 oxidation, and the major oxidation products of this cysteine were Cys-SO2H and Cys-SO3H. The oxidation of Cys43 might be responsible for the inactivation of the enzyme upon H2O2 treatment.

  11. Biology, Genetics, and Environment: Underlying Factors Influencing Alcohol Metabolism.

    Science.gov (United States)

    Wall, Tamara L; Luczak, Susan E; Hiller-Sturmhöfel, Susanne

    2016-01-01

    Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects. The prevalence of these alleles differs among ethnic groups; ADH1B*2 is found frequently in northeast Asians and occasionally Caucasians, ADH1B*3 is found predominantly in people of African ancestry, ADH1C*1 varies substantially across populations, and ALDH2*2 is found almost exclusively in northeast Asians. Differences in the prevalence of these alleles may account at least in part for ethnic differences in alcohol consumption and alcohol use disorder (AUD). However, these alleles do not act in isolation to influence the risk of AUD. For example, the gene effects of ALDH2*2 and ADH1B*2 seem to interact. Moreover, other factors have been found to influence the extent to which these alleles affect a person's alcohol involvement, including developmental stage, individual characteristics (e.g., ethnicity, antisocial behavior, and behavioral undercontrol), and environmental factors (e.g., culture, religion, family environment, and childhood adversity).

  12. Biology, Genetics, and Environment: Underlying Factors Influencing Alcohol Metabolism.

    Science.gov (United States)

    Wall, Tamara L; Luczak, Susan E; Hiller-Sturmhöfel, Susanne

    2016-01-01

    Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects. The prevalence of these alleles differs among ethnic groups; ADH1B*2 is found frequently in northeast Asians and occasionally Caucasians, ADH1B*3 is found predominantly in people of African ancestry, ADH1C*1 varies substantially across populations, and ALDH2*2 is found almost exclusively in northeast Asians. Differences in the prevalence of these alleles may account at least in part for ethnic differences in alcohol consumption and alcohol use disorder (AUD). However, these alleles do not act in isolation to influence the risk of AUD. For example, the gene effects of ALDH2*2 and ADH1B*2 seem to interact. Moreover, other factors have been found to influence the extent to which these alleles affect a person's alcohol involvement, including developmental stage, individual characteristics (e.g., ethnicity, antisocial behavior, and behavioral undercontrol), and environmental factors (e.g., culture, religion, family environment, and childhood adversity). PMID:27163368

  13. Genes Encoding Enzymes Involved in Ethanol Metabolism

    Science.gov (United States)

    Hurley, Thomas D.; Edenberg, Howard J.

    2012-01-01

    The effects of beverage alcohol (ethanol) on the body are determined largely by the rate at which it and its main breakdown product, acetaldehyde, are metabolized after consumption. The main metabolic pathway for ethanol involves the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Seven different ADHs and three different ALDHs that metabolize ethanol have been identified. The genes encoding these enzymes exist in different variants (i.e., alleles), many of which differ by a single DNA building block (i.e., single nucleotide polymorphisms [SNPs]). Some of these SNPs result in enzymes with altered kinetic properties. For example, certain ADH1B and ADH1C variants that are commonly found in East Asian populations lead to more rapid ethanol breakdown and acetaldehyde accumulation in the body. Because acetaldehyde has harmful effects on the body, people carrying these alleles are less likely to drink and have a lower risk of alcohol dependence. Likewise, an ALDH2 variant with reduced activity results in acetaldehyde buildup and also has a protective effect against alcoholism. In addition to affecting drinking behaviors and risk for alcoholism, ADH and ALDH alleles impact the risk for esophageal cancer. PMID:23134050

  14. Isolation of liver aldehyde oxidase containing fractions from different animals and determination of kinetic parameters for benzaldehyde

    Directory of Open Access Journals (Sweden)

    Kadam R

    2008-01-01

    Full Text Available Aldehyde oxidase activity containing fractions from rabbit, guinea pig, rat and mouse livers were obtained by heat treatment and ammonium sulfate precipitation. Aldehyde oxidase activity was observed in rabbit and guinea pig livers, while aldehyde oxidase activity was absent in rat and mouse liver fractions. Enzyme kinetic parameters, K m and V max , were determined for the oxidation of benzaldehyde to benzoic acid by rabbit and guinea pig liver fractions, by spectrophotometric method, with potassium ferricyanide as the electron acceptor. The K m values obtained for both animal liver fractions were in the range of 10.3-19.1 µM.

  15. Cancer stem cells are new vistas for predicting the course of breast cancer

    Directory of Open Access Journals (Sweden)

    E. A. Maslyukova

    2015-01-01

    Full Text Available Despite progress in treating breast cancer (BC using a combined approach in view of morphological findings, distant metastases may develop in 30–90 % of patients with primary BC even at its early stages. The cancer stem cell (CSC theory is one of the versions that could at least partially explain therapeutic inefficiency. This theory suggests that cancer may occur and arise from a small proportion of stem cells that are able to induce tumor growth and to affect resistance to chemoand radiotherapy. CSCs were identified in different malignant tumors, including BC, cancer of the prostate, colon, pancreas, head and neck, melanoma, and multiple myelomas. This investigation analyzed aldehyde dehydrogenase type 1 (ALDH1 expression in patients with BC. Moreover, the investigators examined the relationship between this marker and the clinical and pathological features of BC. The investigation enrolled 83 locally advanced BC (T1–4N0–3M0 patients treated in 2005 to 2009. To detect CSCs, 83 histological specimens obtained at biopsy in BC patients treated at the Russian Research Center for Radiology and Surgical Technologies underwent immunohistochemical examination for ALDH1 according to the developed protocol. Analysis of a relationship between time to metastases and ALDH1 expression showed a statistically significant decrease in time to disease progression in BC patients with high ALDH1 expression versus those with low ALDH1 expression. The similar trend was observed in overall survival. The survival of patients with less than 1 % ALDH1 expression in the cancer cells was statistically higher than that in the patients with high ALDH1 expression (more than 1 %. 

  16. Selective Production of Aromatic Aldehydes from Heavy Fraction of Bio-oil via Catalytic Oxidation

    International Nuclear Information System (INIS)

    High value-added aromatic aldehydes (e. g. vanillin and syringaldehyde) were produced from heavy fraction of bio-oil (HFBO) via catalytic oxidation. The concept is based on the use of metalloporphyin as catalyst and hydrogen peroxide (H2O2) as oxidant under alkaline condition. The biomimetic catalyst cobalt(II)-sulfonated tetraphenylporphyrin (Co(TPPS4)) was prepared and characterized. It exhibited relative high activity in the catalytic oxidation of HFBO. 4.57 wt % vanillin and 1.58 wt % syringaldehyde were obtained from catalytic oxidation of HFBO, compared to 2.6 wt % vanillin and 0.86 wt % syringaldehyde without Co(TPPS4). Moreover, a possible mechanism of HFBO oxidation using Co(TPPS4)/H2O2 was proposed by the research of model compounds. The results showed that this is a promising and environmentally friendly method for production of aromatic aldehydes from HFBO under Co(TPPS4)/H2O2 system

  17. Selective deoxygenation of aldehydes and alcohols on molybdenum carbide (Mo2C) surfaces

    Science.gov (United States)

    Xiong, Ke; Yu, Weiting; Chen, Jingguang G.

    2014-12-01

    The selective deoxygenation of aldehydes and alcohols without cleaving the Csbnd C bond is crucial for upgrading bio-oil and other biomass-derived molecules to useful fuels and chemicals. In this work, propanal, 1-propanol, furfural and furfuryl alcohol were selected as probe molecules to study the deoxygenation of aldehydes and alcohols on molybdenum carbide (Mo2C) prepared over a Mo(1 1 0) surface. The reaction pathways were investigated using temperature programmed desorption (TPD) and high resolution electron energy loss spectroscopy (HREELS). The deoxygenation of propanal and 1-propanol went through a similar intermediate (propoxide or η2(C,O)-propanal) to produce propene. The deoxygenation of furfural and furfuryl alcohol produced a surface intermediate similar to adsorbed 2-methylfuran. The comparison of these results revealed the promising deoxygenation performance of Mo2C, as well as the effect of the furan ring on the selective deoxygenation of the Cdbnd O and Csbnd OH bonds.

  18. Biomass Vanillin-Derived Polymeric Microspheres Containing Functional Aldehyde Groups: Preparation, Characterization, and Application as Adsorbent.

    Science.gov (United States)

    Zhang, Huanyu; Yong, Xueyong; Zhou, Jinyong; Deng, Jianping; Wu, Youping

    2016-02-01

    The contribution reports the first polymeric microspheres derived from a biomass, vanillin. It reacted with methacryloyl chloride, providing monomer vanillin methacrylate (VMA), which underwent suspension polymerization in aqueous media and yielded microspheres in high yield (>90 wt %). By controlling the N2 bubbling mode and by optimizing the cosolvent for dissolving the solid monomer, the microspheres were endowed with surface pores, demonstrated by SEM images and mercury intrusion porosimetry measurement. Taking advantage of the reactive aldehyde groups, the microspheres further reacted with glycine, thereby leading to a novel type of Schiff-base chelating material. The functionalized microspheres demonstrated remarkable adsorption toward Cu(2+) (maximum, 135 mg/g) which was taken as representative for metal ions. The present study provides an unprecedented class of biobased polymeric microspheres showing large potentials as adsorbents in wastewater treatment. Also importantly, the reactive aldehyde groups may enable the microspheres to be used as novel materials for immobilizing biomacromolecules, e.g. enzymes.

  19. Biomass Vanillin-Derived Polymeric Microspheres Containing Functional Aldehyde Groups: Preparation, Characterization, and Application as Adsorbent.

    Science.gov (United States)

    Zhang, Huanyu; Yong, Xueyong; Zhou, Jinyong; Deng, Jianping; Wu, Youping

    2016-02-01

    The contribution reports the first polymeric microspheres derived from a biomass, vanillin. It reacted with methacryloyl chloride, providing monomer vanillin methacrylate (VMA), which underwent suspension polymerization in aqueous media and yielded microspheres in high yield (>90 wt %). By controlling the N2 bubbling mode and by optimizing the cosolvent for dissolving the solid monomer, the microspheres were endowed with surface pores, demonstrated by SEM images and mercury intrusion porosimetry measurement. Taking advantage of the reactive aldehyde groups, the microspheres further reacted with glycine, thereby leading to a novel type of Schiff-base chelating material. The functionalized microspheres demonstrated remarkable adsorption toward Cu(2+) (maximum, 135 mg/g) which was taken as representative for metal ions. The present study provides an unprecedented class of biobased polymeric microspheres showing large potentials as adsorbents in wastewater treatment. Also importantly, the reactive aldehyde groups may enable the microspheres to be used as novel materials for immobilizing biomacromolecules, e.g. enzymes. PMID:26752344

  20. Generation of thiols by biotransformation of cysteine-aldehyde conjugates with baker's yeast.

    Science.gov (United States)

    Huynh-Ba, Tuong; Matthey-Doret, Walter; Fay, Laurent B; Bel Rhlid, Rachid

    2003-06-01

    Baker's yeast was shown to catalyze the transformation of cysteine-furfural conjugate into 2-furfurylthiol. The biotransformation's yield and kinetics were influenced by the reaction parameters such as pH, incubation mode (aerobic and anaerobic), and substrate concentration. 2-Furfurylthiol was obtained in an optimal 37% yield when cysteine-furfural conjugate at a 20 mM concentration was anaerobically incubated with whole cell baker's yeast at pH 8.0 and 30 degrees C. Similarly to 2-furfurylthiol, 5-methyl-2-furfurylthiol (11%), benzylthiol (8%), 2-thiophenemethanethiol (22%), 3-methyl-2-thiophenemethanethiol (3%), and 2-pyrrolemethanethiol (6%) were obtained from the corresponding cysteine-aldehyde conjugates by incubation with baker's yeast. This work indicates the versatile bioconversion capacity of baker's yeast for the generation of thiols from cysteine-aldehyde conjugates. Thanks to its food-grade character, baker's yeast provides a biochemical tool to produce thiols, which can be used as flavorings in foods and beverages.

  1. Synthesis of Tetrahydronaphthyridines from Aldehydes and HARP Reagents via Radical Pictet-Spengler Reactions.

    Science.gov (United States)

    Jackl, Moritz K; Kreituss, Imants; Bode, Jeffrey W

    2016-04-15

    The combination of aldehydes with newly designed HARP (halogen amine radical protocol) reagents gives access to α-substituted tetrahydronaphthyridines. By using different HARP reagents, various regioisomeric structures can be prepared in a single operation. These products, which are of high value in medicinal chemistry, are formed in a predictable manner via a formal Pictet-Spengler reaction of electron-poor pyridines that would not participate in the corresponding polar reactions. PMID:27026179

  2. "Dopamine-first" mechanism enables the rational engineering of the norcoclaurine synthase aldehyde activity profile

    OpenAIRE

    Lichman, B. R.; Gershater, M. C.; Lamming, E. D.; Pesnot, T.; Sula, A.; Keep, N.H.; Hailes, H. C.; Ward, J. M.

    2015-01-01

    Norcoclaurine synthase (NCS) (EC 4.2.1.78) catalyzes the Pictet-Spengler condensation of dopamine and an aldehyde, forming a substituted (S)-tetrahydroisoquinoline, a pharmaceutically important moiety. This unique activity has led to NCS being used for both in vitro biocatalysis and in vivo recombinant metabolism. Future engineering of NCS activity to enable the synthesis of diverse tetrahydroisoquinolines is dependent on an understanding of the NCS mechanism and kinetics. We assess two propo...

  3. Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

    Directory of Open Access Journals (Sweden)

    Xacobe C. Cambeiro

    2011-10-01

    Full Text Available The application of polystyrene-immobilized proline-based catalysts in packed-bed reactors for the continuous-flow, direct, enantioselective α-aminoxylation of aldehydes is described. The system allows the easy preparation of a series of β-aminoxy alcohols (after a reductive workup with excellent optical purity and with an effective catalyst loading of ca. 2.5% (four-fold reduction compared to the batch process working at residence times of ca. 5 min.

  4. Ambient concentrations of aldehydes in relation to Beijing Olympic air pollution control measures

    Directory of Open Access Journals (Sweden)

    J. C. Gong

    2010-08-01

    Full Text Available Aldehydes are ubiquitous constituents of the atmosphere. Their concentrations are elevated in polluted urban atmospheres. The present study was carried out to characterize three aldehydes of most health concern (formaldehyde, acetaldehyde, and acrolein in a central Beijing site in the summer and early fall of 2008 (from June to October. Measurements were made before, during, and after the Beijing Olympics to examine whether the air pollution control measures implemented to improve Beijing's air quality during the Olympics had any impact on concentrations of the three aldehydes. Average concentrations of formaldehyde, acetaldehyde and acrolein were 29.34 ± 15.12 μg/m3, 27.09 ± 15.74 μg/m3 and 2.32 ± 0.95 μg/m3, respectively, for the entire period of measurements, all being the highest among the levels measured in cities around the world in photochemical smog seasons. Among the three measured aldehydes, only acetaldehyde had a substantially reduced mean concentration during the Olympic air pollution control period compared to the pre-Olympic period. Formaldehyde and acrolein followed the changing pattern of temperature and were each significantly correlated with ozone (a secondary product of photochemical reactions. In contrast, acetaldehyde was significantly correlated with several pollutants emitted mainly from local emission sources (e.g., NO2, CO, and PM2.5. These findings suggest that local direct emissions had a larger impact on acetaldehyde than formaldehyde and acrolein.

  5. Small Peptides Catalyzed Direct Aldol Reactions of Aldehydes with Hydroxyacetone with Regiocontrol in Aqueous Media

    Institute of Scientific and Technical Information of China (English)

    TANG,Zhuo; YANG,Zhi-Hua; CUN,Lin-Feng; GONG,Liu-Zhu; MI,Ai-Qiao; JIANG,Yao-Zhong

    2004-01-01

    @@ Very recently, we[1] found that L-proline amides and dipeptides acted as efficient catalysts for the asymmetric direct aldol reaction. We report here that L-proline-based peptides 1~5 can catalyze the aldol reactions of hydroxyacetone with aldehydes 6 in aqueous media, to give 1,4-diols (7), the disfavored products with either aldolase or L-proline. Both peptides 3 and 4 give good results.

  6. Three-Component Halo Aldol Condensation of Thioacrylates with Aldehydes Mediated by Titanium (IV Halide

    Directory of Open Access Journals (Sweden)

    Guigen Li

    2002-01-01

    Full Text Available a,b-Ethyl thioacrylate was difuctionalized by a tandem X-C/C=C bond formation reaction. The new system uses Ti (IV halide as both the Lewis acidic promoter and the halogen source for the Michael-type addition onto the thioacrylate. The titanium enolate species resulting from Michael-type addition react with aldehydes followed by dehydration to afford trisubstituted olefin products. Complete geometric selectivity (>95% and up to 72% yield have been obtained for 7 examples.

  7. Three-Component Halo Aldol Condensation of Thioacrylates with Aldehydes Mediated by Titanium (IV) Halide

    OpenAIRE

    Guigen Li; Gao, Joe J.; Han-Xun Wei; Sun Hee Kim

    2002-01-01

    a,b-Ethyl thioacrylate was difuctionalized by a tandem X-C/C=C bond formation reaction. The new system uses Ti (IV) halide as both the Lewis acidic promoter and the halogen source for the Michael-type addition onto the thioacrylate. The titanium enolate species resulting from Michael-type addition react with aldehydes followed by dehydration to afford trisubstituted olefin products. Complete geometric selectivity (>95%) and up to 72% yield have been obtained for 7 examples.

  8. Reactions of CH-acids with α,β-unsaturated aldehydes in ionic liquids

    DEFF Research Database (Denmark)

    Kryshtal, G. V.; Zhdankina, G. M.; Astakhova, Irina Kira;

    2004-01-01

    Metal carbonate-catalyzed reactions of CH-acids (diethyl malonate, ethyl acetoacetate, ethyl cyanoacetate, and ethyl 2-acetyl- and 2-ethoxycarbonyl-5,9- dimethyldeca-4,8-dienoates) with α,β-unsaturated aldehydes (acrolein, crotonaldehyde, citral) were studied in an ionic liquid, 1-butyl-3...... of the Michael adducts. The ionic liquid [bmim][PF 6] can be recovered and repeatedly used in the reactions....

  9. Aldehydes in relation to air pollution sources: A case study around the Beijing Olympics

    Science.gov (United States)

    Altemose, Brent; Gong, Jicheng; Zhu, Tong; Hu, Min; Zhang, Liwen; Cheng, Hong; Zhang, Lin; Tong, Jian; Kipen, Howard M.; Ohman-Strickland, Pamela; Meng, Qingyu; Robson, Mark G.; Zhang, Junfeng

    2015-05-01

    This study was carried out to characterize three aldehydes of health concern (formaldehyde, acetaldehyde, and acrolein) at a central Beijing site in the summer and early fall of 2008 (from June to October). Aldehydes in polluted atmospheres come from both primary and secondary sources, which limits the control strategies for these reactive compounds. Measurements were made before, during, and after the Beijing Olympics to examine whether the dramatic air pollution control measures implemented during the Olympics had an impact on concentrations of the three aldehydes and their underlying primary and secondary sources. Average concentrations of formaldehyde, acetaldehyde and acrolein were 29.3 ± 15.1 μg/m3, 27.1 ± 15.7 μg/m3 and 2.3 ± 1.0 μg/m3, respectively, for the entire period of measurements, all being at the high end of concentration ranges measured in cities around the world in photochemical smog seasons. Formaldehyde and acrolein increased during the pollution control period compared to the pre-Olympic Games, followed the changing pattern of temperature, and were significantly correlated with ozone and with a secondary formation factor identified by principal component analysis (PCA). In contrast, acetaldehyde had a reduction in mean concentration during the Olympic air pollution control period compared to the pre-Olympic period and was significantly correlated with several pollutants emitted from local emission sources (e.g., NO2, CO, and PM2.5). Acetaldehyde was also more strongly associated with primary emission sources including vegetative burning and oil combustion factors identified through the PCA. All three aldehydes were lower during the post-Olympic sampling period compared to the before and during Olympic periods, likely due to seasonal and regional effects. Our findings point to the complexity of source control strategies for secondary pollutants.

  10. Aqueous DMSO Mediated Conversion of (2-(Arylsulfonyl)vinyl)iodonium Salts to Aldehydes and Vinyl Chlorides.

    Science.gov (United States)

    Zawia, Eman; Moran, Wesley J

    2016-01-01

    Vinyl(aryl)iodonium salts are useful compounds in organic synthesis but they are under-utilized and their chemistry is under-developed. Herein is described the solvolysis of some vinyl(phenyl)iodonium salts, bearing an arylsulfonyl group, in aqueous DMSO leading to aldehyde formation. This unusual process is selective and operates under ambient conditions. Furthermore, the addition of aqueous HCl and DMSO to these vinyl(aryl)iodonium salts allows their facile conversion to vinyl chlorides. PMID:27537866

  11. Primary Amine–2-Aminopyrimidine Chiral Organocatalysts for the Enantioselective Conjugate Addition of Branched Aldehydes to Maleimides

    OpenAIRE

    Vizcaíno-Milla, Pascuala; Sansano Gil, José Miguel; Nájera Domingo, Carmen; Fiser, Béla; Gómez Bengoa, Enrique

    2015-01-01

    Chiral primary amines containing the (R,R)- and (S,S)-trans-cyclohexane-1,2-diamine scaffold and a pyrimidin-2-yl unit are synthesized and used as general organocatalysts for the Michael reaction of α-branched aldehydes to maleimides. The reaction takes place with 10 mol% organocatalyst loading and hexanedioic acid as cocatalyst in aqueous N,N-dimethylformamide at 10 °C affording the corresponding succinimides in good yields and enantioselectivities. DFT calculations support the stereochemica...

  12. Phenolic Acids, Phenolic Aldehydes and Furanic Derivatives in Oak Chips: American vs. French Oaks

    OpenAIRE

    Cabrita, M.J.; Barrocas Dias, C.; Costa Freitas, A.M.

    2011-01-01

    Phenolic acids (gallic, vanillic, syringic and ellagic acids), phenolic aldehydes (vanillin, syringaldehyde, coniferaldehyde and sinapaldehyde) and furanic derivatives (furfural, 5-methylfurfural and 5-hydroxymethylfurfural) were quantified in commercial American and French oak chips. Chips with different sizes and toast degrees were used. Compounds were extracted directly from the wood samples in order to determine possible differences among woods as well as toast degree. Likewise, the compo...

  13. Aerobic oxidation of aldehydes under ambient conditions using supported gold nanoparticle catalysts

    DEFF Research Database (Denmark)

    Marsden, Charlotte Clare; Taarning, Esben; Hansen, David;

    2008-01-01

    A new, green protocol for producing simple esters by selectively oxidizing an aldehyde dissolved in a primary alcohol has been established, utilising air as the oxidant and supported gold nanoparticles as catalyst. The oxidative esterifications proceed with excellent selectivities at ambient cond...... conditions; the reactions can be performed in an open flask and at room temperature. Benzaldehyde is even oxidised at a reasonable rate below -70 degrees C. Acrolein is oxidised to methyl acrylate in high yield using the same protocol....

  14. The concise synthesis of chiral tfb ligands and their application to the rhodium-catalyzed asymmetric arylation of aldehydes

    OpenAIRE

    Nishimura, Takahiro; Kumamoto, Hana; Nagaosa, Makoto; Hayashi, Tamio

    2009-01-01

    New C2-symmetric tetrafluorobenzobarrelene ligands were prepared and applied successfully to the rhodium-catalyzed asymmetric addition of arylboronic acids to aromatic aldehydes giving chiral diarylmethanols in high yield with high enantioselectivity.

  15. Synthesis of chiral N-ferrocenylmethylaminoalcohols and their applica-tion in enantioselective addition of diethylzinc to aldehydes

    Institute of Scientific and Technical Information of China (English)

    Jian Feng GE; Zong Xuan SHEN; Ya Wen ZHANG

    2004-01-01

    Three chiral N-ferrocenylmethylaminoalcohols were synthesized from readily available natural L-valine, leucine and phenylanine, and used as chiral ligands in the enantioselective addition of diethylzinc to aldehydes.

  16. Enantioselective Pinacol Coupling of Aromatic Aldehydes Mediated by TiCl4(THF)2/Zn with Tartaric Ester

    Institute of Scientific and Technical Information of China (English)

    LI You-Gui李有桂; JIANG Chen江辰; ZHAO Jun赵俊; TIAN Qing-Shan田青杉; YOU Tian-Pa尤田耙

    2004-01-01

    Asymmetric pinacol coupling of aromatic aldehydes mediated by low valent titanium complexes of chiral ligands derived from natural tartaric acid provided corresponding pinacols in good yields with excellent diastereoselectivities and moderate enantioselectivities.

  17. New Aldehyde Reductase Genes of Saccharomyces cerevisiae Contribute In Situ Detoxification of Lignocellulose-to-Ethanol Conversion Inhibitiors

    Science.gov (United States)

    Furfural and 5-hydroxymethylfurfural (HMF) are inhibitory compounds commonly encountered during lignocellulose-to-ethanol conversion for cleaner transportation fuels. It is possible to in situ detoxify the aldehyde inhibitors by tolerant ethanologenic yeast strains. Multiple gene-mediated reductio...

  18. Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus.

    Directory of Open Access Journals (Sweden)

    Giovanna Romano

    Full Text Available Diatoms are ubiquitous and abundant primary producers that have been traditionally considered as a beneficial food source for grazers and for the transfer of carbon through marine food webs. However, many diatom species produce polyunsaturated aldehydes that disrupt development in the offspring of grazers that feed on these unicellular algae. Here we provide evidence that production of the physiological messenger nitric oxide increases after treatment with the polyunsaturated aldehyde decadienal in embryos of the sea urchin Paracentrotus lividus. At high decadienal concentrations, nitric oxide mediates initial apoptotic events leading to loss of mitochondrial functionality through the generation of peroxynitrite. At low decadienal concentrations, nitric oxide contributes to the activation of hsp70 gene expression thereby protecting embryos against the toxic effects of this aldehyde. When nitric oxide levels were lowered by inhibiting nitric oxide synthase activity, the expression of hsp70 in swimming blastula decreased and the proportion of abnormal plutei increased. However, in later pluteus stages nitric oxide was no longer able to exert this protective function: hsp70 and nitric oxide synthase expression decreased with a consequent increase in the expression of caspase-8. Our findings that nitric oxide production increases rapidly in response to a toxic exogenous stimulus opens new perspectives on the possible role of this gas as an important messenger to environmental stress in sea urchins and for understanding the cellular mechanisms underlying toxicity during diatom blooms.

  19. Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus.

    Science.gov (United States)

    Romano, Giovanna; Costantini, Maria; Buttino, Isabella; Ianora, Adrianna; Palumbo, Anna

    2011-01-01

    Diatoms are ubiquitous and abundant primary producers that have been traditionally considered as a beneficial food source for grazers and for the transfer of carbon through marine food webs. However, many diatom species produce polyunsaturated aldehydes that disrupt development in the offspring of grazers that feed on these unicellular algae. Here we provide evidence that production of the physiological messenger nitric oxide increases after treatment with the polyunsaturated aldehyde decadienal in embryos of the sea urchin Paracentrotus lividus. At high decadienal concentrations, nitric oxide mediates initial apoptotic events leading to loss of mitochondrial functionality through the generation of peroxynitrite. At low decadienal concentrations, nitric oxide contributes to the activation of hsp70 gene expression thereby protecting embryos against the toxic effects of this aldehyde. When nitric oxide levels were lowered by inhibiting nitric oxide synthase activity, the expression of hsp70 in swimming blastula decreased and the proportion of abnormal plutei increased. However, in later pluteus stages nitric oxide was no longer able to exert this protective function: hsp70 and nitric oxide synthase expression decreased with a consequent increase in the expression of caspase-8. Our findings that nitric oxide production increases rapidly in response to a toxic exogenous stimulus opens new perspectives on the possible role of this gas as an important messenger to environmental stress in sea urchins and for understanding the cellular mechanisms underlying toxicity during diatom blooms. PMID:22022485

  20. ‘Dopamine-first’ mechanism enables the rational engineering of the norcoclaurine synthase aldehyde activity profile

    Science.gov (United States)

    Lichman, Benjamin R; Gershater, Markus C; Lamming, Eleanor D; Pesnot, Thomas; Sula, Altin; Keep, Nicholas H; Hailes, Helen C; Ward, John M

    2015-01-01

    Norcoclaurine synthase (NCS) (EC 4.2.1.78) catalyzes the Pictet–Spengler condensation of dopamine and an aldehyde, forming a substituted (S)-tetrahydroisoquinoline, a pharmaceutically important moiety. This unique activity has led to NCS being used for both in vitro biocatalysis and in vivo recombinant metabolism. Future engineering of NCS activity to enable the synthesis of diverse tetrahydroisoquinolines is dependent on an understanding of the NCS mechanism and kinetics. We assess two proposed mechanisms for NCS activity: (a) one based on the holo X-ray crystal structure and (b) the ‘dopamine-first’ mechanism based on computational docking. Thalictrum flavum NCS variant activities support the dopamine-first mechanism. Suppression of the non-enzymatic background reaction reveals novel kinetic parameters for NCS, showing it to act with low catalytic efficiency. This kinetic behaviour can account for the ineffectiveness of recombinant NCS in in vivo systems, and also suggests NCS may have an in planta role as a metabolic gatekeeper. The amino acid substitution L76A, situated in the proposed aldehyde binding site, results in the alteration of the enzyme's aldehyde activity profile. This both verifies the dopamine-first mechanism and demonstrates the potential for the rational engineering of NCS activity. PMID:25620686

  1. 'Dopamine-first' mechanism enables the rational engineering of the norcoclaurine synthase aldehyde activity profile.

    Science.gov (United States)

    Lichman, Benjamin R; Gershater, Markus C; Lamming, Eleanor D; Pesnot, Thomas; Sula, Altin; Keep, Nicholas H; Hailes, Helen C; Ward, John M

    2015-03-01

    Norcoclaurine synthase (NCS) (EC 4.2.1.78) catalyzes the Pictet-Spengler condensation of dopamine and an aldehyde, forming a substituted (S)-tetrahydroisoquinoline, a pharmaceutically important moiety. This unique activity has led to NCS being used for both in vitro biocatalysis and in vivo recombinant metabolism. Future engineering of NCS activity to enable the synthesis of diverse tetrahydroisoquinolines is dependent on an understanding of the NCS mechanism and kinetics. We assess two proposed mechanisms for NCS activity: (a) one based on the holo X-ray crystal structure and (b) the 'dopamine-first' mechanism based on computational docking. Thalictrum flavum NCS variant activities support the dopamine-first mechanism. Suppression of the non-enzymatic background reaction reveals novel kinetic parameters for NCS, showing it to act with low catalytic efficiency. This kinetic behaviour can account for the ineffectiveness of recombinant NCS in in vivo systems, and also suggests NCS may have an in planta role as a metabolic gatekeeper. The amino acid substitution L76A, situated in the proposed aldehyde binding site, results in the alteration of the enzyme's aldehyde activity profile. This both verifies the dopamine-first mechanism and demonstrates the potential for the rational engineering of NCS activity. PMID:25620686

  2. Pulsed corona discharge oxidation of aqueous lignin: decomposition and aldehydes formation.

    Science.gov (United States)

    Panorel, Iris; Kaijanen, Laura; Kornev, Iakov; Preis, Sergei; Louhi-Kultanen, Marjatta; Sirén, Heli

    2014-01-01

    Lignin is the mass waste product of pulp and paper industry mostly incinerated for energy recovery. Lignin is, however, a substantial source of raw material for derivatives currently produced in costly wet oxidation processes. The pulsed corona discharge (PCD) for the first time was applied to lignin oxidation aiming a cost-effective environmentally friendly lignin removal and transformation to aldehydes. The experimental research into treatment of coniferous kraft lignin aqueous solutions was undertaken to establish the dependence of lignin oxidation and aldehyde formation on the discharge parameters, initial concentration of lignin and gas phase composition. The rate and the energy efficiency of lignin oxidation increased with increasing oxygen concentration reaching up to 82 g kW-1 h-1 in 89% vol. oxygen. Oxidation energy efficiency in PCD treatment exceeds the one for conventional ozonation by the factor of two under the experimental conditions. Oxidation at low oxygen concentrations showed a tendency of the increasing aldehydes and glyoxylic acid formation yield. PMID:24600854

  3. Hydrazide and hydrazine reagents as reactive matrices for MALDI-MS to detect gaseous aldehydes.

    Science.gov (United States)

    Shigeri, Yasushi; Ikeda, Shinya; Yasuda, Akikazu; Ando, Masanori; Sato, Hiroaki; Kinumi, Tomoya

    2014-08-01

    The reagents 19 hydrazide and 14 hydrazine were examined to function as reactive matrices for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to detect gaseous aldehydes. Among them, two hydrazide (2-hydroxybenzohydrazide and 3-hydroxy-2-naphthoic acid hydrazide) and two hydrazine reagents [2-hydrazinoquinoline and 2,4-dinitrophenylhydrazine (DNPH)] were found to react efficiently with carbonyl groups of gaseous aldehydes (formaldehyde, acetaldehyde and propionaldehyde); these are the main factors for sick building syndrome and operate as reactive matrices for MALDI-MS. Results from accurate mass measurements by JMS-S3000 Spiral-TOF suggested that protonated ion peaks corresponding to [M + H](+) from the resulting derivatives were observed in all cases with the gaseous aldehydes in an incubation, time-dependent manner. The two hydrazide and two hydrazine reagents all possessed absorbances at 337 nm (wavelength of MALDI nitrogen laser), with, significant electrical conductivity of the matrix crystal and functional groups, such as hydroxy group and amino group, being important for desorption/ionization efficiency in MALDI-MS. To our knowledge, this is the first report that gaseous molecules could be derivatized and detected directly in a single step by MALDI-MS using novel reactive matrices that were derivatizing agents with the ability to enhance desorption/ionization efficiency. PMID:25044902

  4. Aldehydes, hydrogen peroxide, and organic radicals as mediators of ozone toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Pryor, W.A.; Church, D.F. (Biodynamics Institute, Louisiana State University, Baton Rouge (United States))

    1991-01-01

    It is generally agreed that unsaturated fatty acids (UFA) are an important class of target molecule for reaction with ozone when polluted air is inhaled. Most discussions have implicated the UFA in cell membranes, but lung lining fluids also contain fatty acids that are from 20 to 40% unsaturated. Since UFA in lung lining fluids exist in a highly aquated environment, ozonation would be expected to produce aldehydes and hydrogen peroxide, rather than the Criegee ozonide. In agreement with this expectation, the authors find that ozonations of emulsions of fatty acids containing from one to four double bonds give one mole of H2O2 for each mole of ozone reacted. Ozonation of oleic acid emulsions and dioleoyl phosphatidyl choline gives similar results, with two moles of aldehydes and one mole of H2O2 formed per mole of ozone reacted. The net reaction that occurs when ozone reacts with pulmonary lipids is suggested to be given by equation 1. (formula: see text). From 5 to 10% yields of Criegee ozonides also appear to be formed. In addition, a direct reaction of unknown mechanism occurs between ozone and UFA in homogeneous organic solution, in homogeneous solutions in water, in aqueous emulsions, and in lipid bilayers to give organic radicals that can be spin trapped. These radicals are suggested to be responsible for initiating lipid peroxidation of polyunsaturated fatty acids. Thus, aldehydes, hydrogen peroxide, and directly produced organic radicals are suggested to be mediators of ozone-induced pathology.39 references.

  5. Identification and Quantification of Aldehydes in Mezcal by Solid Phase Microextraction with On-fiber Derivatization - Gas Cromatography

    OpenAIRE

    Guadalupe Medina Valtierra; Rocío Juárez Ciprés; Araceli Peña Álvarez

    2011-01-01

    A headspace solid phase microextraction with on fiber derivatization procedure followed by gas chromatography and flame ionization detection was applied for the determination of aldehydes in mezcal. A derivatization agent o-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine (PFBHA) was adsorbed onto a Polydimethylsiloxane/ divinyl benzene (PDMS/DVB, 65 ¿m) fiber and exposed to the headspace of a vial with a mezcal sample. The aldehydes selectively reacted with PFBHA, and the oximes were desorbed int...

  6. A unified approach for the synthesis of symmetrical and unsymmetrical dibenzyl ethers from aryl aldehydes through reductive etherification

    Directory of Open Access Journals (Sweden)

    J. Sembian Ruso

    2016-05-01

    Full Text Available In this paper, we describe a simple and convenient conversion of aryl aldehydes to symmetrical dibenzyl ethers through reductive etherification. Similarly, unsymmetrical dibenzyl ether was obtained from aryl aldehyde and TES-protected benzyl alcohol. Triethyl silane with catalytic amount of InCl3 was found to be an efficient condition for the reductive etherification. Moreover, it exhibits remarkable functional group compatibility with yield ranging from good to excellent.

  7. Haplotype-Based Study of the Association of Alcohol Metabolizing Genes with Alcohol Dependence in Four Independent Populations

    Science.gov (United States)

    Liu, Jixia; Zhou, Zhifeng; Hodgkinson, Colin A.; Yuan, Qiaoping; Shen, Pei-Hong; Mulligan, Connie J.; Wang, Alex; Gray, Rebecca R.; Roy, Alec; Virkkunen, Matti; Goldman, David; Enoch, Mary-Anne

    2010-01-01

    Background Ethanol is metabolized by two rate limiting reactions: alcohol dehydrogenases (ADH) convert ethanol to acetaldehyde, subsequently metabolized to acetate by aldehyde dehydrogenases (ALDH). Approximately 50% of East Asians have genetic variants that significantly impair this pathway and influence alcohol dependence (AD) vulnerability. We investigated whether variation in alcohol metabolism genes might alter the AD risk in four non-East Asian populations by performing systematic haplotype association analyses in order to maximize the chances of capturing functional variation. Methods Haplotype-tagging SNPs were genotyped using the Illumina GoldenGate platform. Genotypes were available for 40 SNPs across the ADH genes cluster and 24 SNPs across the two ALDH genes in four diverse samples that included cases (lifetime AD) and controls (no Axis 1 disorders). The case, control sample sizes were: Finnish Caucasians: 232, 194; African Americans: 267, 422; Plains American Indians: 226, 110; Southwestern American (SW) Indians: 317, 72. Results In all four populations, as well as HapMap populations, five haplotype blocks were identified across the ADH gene cluster: (1) ADH5-ADH4; (2) ADH6-ADH1A-ADH1B; (3) ADH1C; (4) intergenic; (5) ADH7. The ALDH1A1 gene was defined by four blocks and ALDH2 by one block. No haplotype or SNP association results were significant after correction for multiple comparisons; however several results, particularly for ALDH1A1 and ADH4, replicated earlier findings. There was an ALDH1A1 block 1 and 2 (extending from intron 5 to the 3′ UTR) yin yang haplotype (haplotypes that have opposite allelic configuration) association with AD in the Finns driven by SNPs rs3764435 and rs2303317 respectively, and an ALDH1A1 block 3 (including the promoter region) yin yang haplotype association in SW Indians driven by 5 SNPs, all in allelic identity. The ADH4 SNP rs3762894 was associated with AD in Plains Indians. Conclusions The systematic evaluation of

  8. [Features of glutamate dehydrogenase in fetal and adult rumen tissue].

    Science.gov (United States)

    Kalachniuk, H I; Fomenko, I S; Kalachniuk, L H; Kavai, Sh; Marounek, M; Savka, O H

    2001-01-01

    Glutamate dehydrogenase (GDH) from rumen mucosa of cow fetus, liver and two forms from mucosa (bacterial and tissue) of the adult animal were partly purified and characterized. The activity of the bacterial glutamate dehydrogenase was shown to depend on qualities of a biomass of microbes, adhered on surface of rumen mucosa. All enzymes from tissues (GDHTRF, TRC, TLC), revealed the hypersensibility to increase in the concentration medium of Zn2+, guanosine triphosphate (GTP), acting here in a role of negative modulators, and also adenosine monophosphate (AMP) and leucine, which acted as activators. However, in the same concentrations these effectors do not influence the activity of the bacterial glutamate dehydrogenase. And if all tissues enzymes are highly specific to coenzyme NADH, the bacterial ones almost in 3 times is more active at NADPH use. PMID:11642036

  9. Aminotransferase and glutamate dehydrogenase activities in lactobacilli and streptococci.

    Science.gov (United States)

    Peralta, Guillermo Hugo; Bergamini, Carina Viviana; Hynes, Erica Rut

    2016-01-01

    Aminotransferases and glutamate dehydrogenase are two main types of enzymes involved in the initial steps of amino acid catabolism, which plays a key role in the cheese flavor development. In the present work, glutamate dehydrogenase and aminotransferase activities were screened in twenty one strains of lactic acid bacteria of dairy interest, either cheese-isolated or commercial starters, including fifteen mesophilic lactobacilli, four thermophilic lactobacilli, and two streptococci. The strains of Streptococcus thermophilus showed the highest glutamate dehydrogenase activity, which was significantly elevated compared with the lactobacilli. Aspartate aminotransferase prevailed in most strains tested, while the levels and specificity of other aminotransferases were highly strain- and species-dependent. The knowledge of enzymatic profiles of these starter and cheese-isolated cultures is helpful in proposing appropriate combinations of strains for improved or increased cheese flavor. PMID:27266631

  10. Aminotransferase and glutamate dehydrogenase activities in lactobacilli and streptococci.

    Science.gov (United States)

    Peralta, Guillermo Hugo; Bergamini, Carina Viviana; Hynes, Erica Rut

    2016-01-01

    Aminotransferases and glutamate dehydrogenase are two main types of enzymes involved in the initial steps of amino acid catabolism, which plays a key role in the cheese flavor development. In the present work, glutamate dehydrogenase and aminotransferase activities were screened in twenty one strains of lactic acid bacteria of dairy interest, either cheese-isolated or commercial starters, including fifteen mesophilic lactobacilli, four thermophilic lactobacilli, and two streptococci. The strains of Streptococcus thermophilus showed the highest glutamate dehydrogenase activity, which was significantly elevated compared with the lactobacilli. Aspartate aminotransferase prevailed in most strains tested, while the levels and specificity of other aminotransferases were highly strain- and species-dependent. The knowledge of enzymatic profiles of these starter and cheese-isolated cultures is helpful in proposing appropriate combinations of strains for improved or increased cheese flavor.

  11. Kinetics of Forming Aldehydes in Frying Oils and Their Distribution in French Fries Revealed by LC-MS-Based Chemometrics.

    Science.gov (United States)

    Wang, Lei; Csallany, A Saari; Kerr, Brian J; Shurson, Gerald C; Chen, Chi

    2016-05-18

    In this study, the kinetics of aldehyde formation in heated frying oils was characterized by 2-hydrazinoquinoline derivatization, liquid chromatography-mass spectrometry (LC-MS) analysis, principal component analysis (PCA), and hierarchical cluster analysis (HCA). The aldehydes contributing to time-dependent separation of heated soybean oil (HSO) in a PCA model were grouped by the HCA into three clusters (A1, A2, and B) on the basis of their kinetics and fatty acid precursors. The increases of 4-hydroxynonenal (4-HNE) and the A2-to-B ratio in HSO were well-correlated with the duration of thermal stress. Chemometric and quantitative analysis of three frying oils (soybean, corn, and canola oils) and French fry extracts further supported the associations between aldehyde profiles and fatty acid precursors and also revealed that the concentrations of pentanal, hexanal, acrolein, and the A2-to-B ratio in French fry extracts were more comparable to their values in the frying oils than other unsaturated aldehydes. All of these results suggest the roles of specific aldehydes or aldehyde clusters as novel markers of the lipid oxidation status for frying oils or fried foods.

  12. Kinetics of Forming Aldehydes in Frying Oils and Their Distribution in French Fries Revealed by LC-MS-Based Chemometrics.

    Science.gov (United States)

    Wang, Lei; Csallany, A Saari; Kerr, Brian J; Shurson, Gerald C; Chen, Chi

    2016-05-18

    In this study, the kinetics of aldehyde formation in heated frying oils was characterized by 2-hydrazinoquinoline derivatization, liquid chromatography-mass spectrometry (LC-MS) analysis, principal component analysis (PCA), and hierarchical cluster analysis (HCA). The aldehydes contributing to time-dependent separation of heated soybean oil (HSO) in a PCA model were grouped by the HCA into three clusters (A1, A2, and B) on the basis of their kinetics and fatty acid precursors. The increases of 4-hydroxynonenal (4-HNE) and the A2-to-B ratio in HSO were well-correlated with the duration of thermal stress. Chemometric and quantitative analysis of three frying oils (soybean, corn, and canola oils) and French fry extracts further supported the associations between aldehyde profiles and fatty acid precursors and also revealed that the concentrations of pentanal, hexanal, acrolein, and the A2-to-B ratio in French fry extracts were more comparable to their values in the frying oils than other unsaturated aldehydes. All of these results suggest the roles of specific aldehydes or aldehyde clusters as novel markers of the lipid oxidation status for frying oils or fried foods. PMID:27128101

  13. Crystal structure of homoisocitrate dehydrogenase from Schizosaccharomyces pombe

    Energy Technology Data Exchange (ETDEWEB)

    Bulfer, Stacie L.; Hendershot, Jenna M.; Trievel, Raymond C. (Michigan); (UCSF)

    2013-09-18

    Lysine biosynthesis in fungi, euglena, and certain archaebacteria occurs through the {alpha}-aminoadipate pathway. Enzymes in the first steps of this pathway have been proposed as potential targets for the development of antifungal therapies, as they are absent in animals but are conserved in several pathogenic fungi species, including Candida, Cryptococcus, and Aspergillus. One potential antifungal target in the {alpha}-aminoadipate pathway is the third enzyme in the pathway, homoisocitrate dehydrogenase (HICDH), which catalyzes the divalent metal-dependent conversion of homoisocitrate to 2-oxoadipate (2-OA) using nicotinamide adenine dinucleotide (NAD{sup +}) as a cofactor. HICDH belogns to a family of {beta}-hydroxyacid oxidative decarboxylases that includes malate dehydrogenase, tartrate dehydrogenase, 6-phosphogluconate dehydrogenase, isocitrate dehydrogenase (ICDH), and 3-isopropylmalte dehydrogenase (IPMDH). ICDH and IPMDH are well-characterized enzymes that catalyze the decarboxylation of isocitrate to yield 2-oxoglutarate (2-OG) in the citric acid cycle and the conversion of 3-isopropylmalate to 2-oxoisovalerate in the leucine biosynthetic pathway, respectively. Recent structural and biochemical studies of HICDH reveal that this enzyme shares sequence, structural, and mechanistic homology with ICDH and IPMDH. To date, the only published structures of HICDH are from the archaebacteria Thermus thermophilus (TtHICDH). Fungal HICDHs diverge from TtHICDH in several aspects, including their thermal stability, oligomerization state, and substrate specificity, thus warranting further characterization. To gain insights into these differences, they determined crystal structures of a fungal Schizosaccharomyces pombe HICDH (SpHICDH) as an apoenzyme and as a binary complex with additive tripeptide glycyl-glycyl-glycine (GGG) to 1.55 {angstrom} and 1.85 {angstrom} resolution, respectively. Finally, a comparison of the SpHICDH and TtHICDH structures reveal differences in

  14. Expression and Significance of Cancer Stem Cell Markers CD133, CD44, SOX2, OCT4 and ALDH1 in Non-small Cell Lung Cancer%肿瘤干细胞标志物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌组织中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    梁洪享; 钟竑; 罗勇; 黄燕; 丁昭珩; 丁罡

    2013-01-01

    目的 研究肿瘤干细胞标记物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌(NSCLC)组织中的表达及临床意义,为探索非小细胞肺癌肿瘤干细胞提供参考.方法 采用免疫组织化学方法检测70例NSCLC组织、14例非癌组织中的CD133、CD44、SOX2、OCT4、ALDH1蛋白的表达并对结果进行分析. 结果 (1) CD133、CD44、SOX2、OCT4、ALDH1在70例NSCLC组织中的阳性表达率分别为88.57%、98.57%、100%、100%、100%,强阳性表达率分别为48.57%、67.14%、67.14%、31.43%、50%; CD133、CCD44在NSCLC与非癌组织中的表达差异存在统计学意义(P均<0.0001),SOX2、OCT4、ALDH1在NSCLC与非癌组织中的表达差异无统计学意义(P均>0.05) (2)随着病理级别的升高,CD133、CD44、SOX2、OCT4及ALDH1的表达呈上升趋势,分化越低的NSCLC表达上述指标的概率越高,其中CD133、SOX2、OCT4的表达在高、中、低分化组织中差异存在统计学意义(P值分别为0.001、0.040、<0.0001);CD133的表达在吸烟史、分化程度、淋巴结转移、肿瘤分期四个因素上差异存在统计学意义(P值分别为0.033、0.001、0.033、0.046);CD44与SOX2的表达在年龄上的差异存在统计学意义(P值分别为0.001、0.040) 结论 NSCLC组织中CD133、CD44、SOX2、OCT4、ALDH1阳性率高,CD133、CD44的表达明显高于非癌组织;CD133、SOX2、OCT4与NSCLC的恶性程度有关;CD44与SOX2与年龄因素有关.

  15. Resveratrol Protects against Chronic Alcoholic Liver Injury by Regulating Hepatic ALDH2 Expression in Rats%A LD H2在白藜芦醇改善大鼠慢性酒精性肝损伤中的机制

    Institute of Scientific and Technical Information of China (English)

    黄丙清; 邱香; 王林枝; 朱腾世; 郭琰芳; 郝丽萍

    2015-01-01

    Objective To evaluate the protective effects of resveratrol (Res)on chronic alcoholic liver injury in rats and fur‐ther explore the underlying mechanism involving hepatic ethanol metabolizing enzymes (ADH and ALDH2).Methods Alcoholic liver injury models of rat were established by feeding Lieber‐DeCarli liquid ethanol diet for 19 weeks. Forty‐two SD rats were randomly divided into normal control group ,low‐,middle‐and high‐dose ethanol groups ,Res control group and high‐dose etha‐nol +Res group. The morphological change of hepatic tissues was observed by hematoxylin‐eosin(HE)and oil red O staining ;the activity of hepatic ADH and ALDH2 was determined by using appropriate kits ;and the protein expressions of hepatic ADH and ALDH2 were detected by Western blot.Results There were serious hepatic steatosis and inflammation in ethanol groups.Body weight and food intake were significantly decreased in the ethanol groups compared with the normal control group. There was moderate increase in the ADH activity and expression and significant decrease in ALDH 2 activity and expres‐sion in ethanol groups.Res could ameliorate ethanol‐induced hepatic steatosis and inflammation as well as increase body weight and energy intake. Hepatic ALDH2 activity and protein expression were significantly increased by Res treatment (P<0.05) . Conclusion Res could improve chronic ethanol‐induced liver injury by regulating hepatic ALDH 2 expression.%目的:探讨酒精代谢酶乙醇脱氢酶(ADH)和乙醛脱氢酶2(ALDH2)在白藜芦醇(resveratrol ,Res)改善大鼠慢性酒精性肝损伤中的机制。方法采用含酒精的Lieber‐DeCarli液体饲料喂养大鼠19周,建立慢性酒精性肝损伤模型。42只SD大鼠随机分成正常对照组,低、中、高剂量酒精组,Res对照组,高剂量酒精+ Res组。采用苏木精‐伊红(HE)和油红O染色,观察肝组织形态学改变;采用试剂盒测定肝组织中ADH、ALDH2

  16. Properties of Lactate Dehydrogenase in a Psychrophilic Marine Bacterium

    OpenAIRE

    Mitchell, P; Yen, H. C.; Mathemeier, P. F.

    1985-01-01

    Lactate dehydrogenase (EC 1.1.1.27) from Vibrio marinus MP-1 was purified 15-fold and ammonium activated. The optimum pH for pyruvate reduction was 7.4. Maximum lactate dehydrogenase activity occurred at 10 to 15 degrees C, and none occurred at 40 degrees C. The crude-extract enzyme was stable between 15 and 20 degrees C and lost 50% of its activity after 60 min at 45 degrees C. The partially purified enzyme was stable between 8 and 15 degrees C and lost 50% of its activity after 60 min at 30...

  17. Purification and characterization of 3-isopropylmalate dehydrogenase from Thiobacillus thiooxidans.

    Science.gov (United States)

    Kawaguchi, H; Inagaki, K; Matsunami, H; Nakayama, Y; Tano, T; Tanaka, H

    2000-01-01

    3-Isopropylmalate dehydrogenase was purified to homogeneity from the acidophilic autotroph Thiobacillus thiooxidans. The native enzyme was a dimer of molecular weight 40,000. The apparent K(m) values for 3-isopropylmalate and NAD+ were estimated to be 0.13 mM and 8.7 mM, respectively. The optimum pH for activity was 9.0 and the optimum temperature was 65 degrees C. The properties of the enzyme were similar to those of the Thiobacillus ferrooxidans enzyme, expect for substrate specificity. T. thiooxidans 3-isopropylmalate dehydrogenase could not utilize malate as a substrate.

  18. Prostaglandin dehydrogenase and the initiation of labor.

    Science.gov (United States)

    Challis, J R; Patel, F A; Pomini, F

    1999-01-01

    In summary, these studies have suggested that prostaglandin dehydrogenase may have a central role to play in the mechanisms which determine biologically active prostaglandin concentrations within human fetal membranes and placenta at the time of labor, at term or preterm. Moreover, our studies indicate that the regulation of PGDH may by multifactorial (figure 3). In certain regions of the membranes, we suggest that PGDH expression may be influenced by levels of anti-inflammatory and pro-inflammatory cytokines. In other regions of the membranes, we suggest that PGDH may be regulated at a transcriptional level by competing activities of progesterone and cortisol. The action of progesterone could be effected through systemically-derived steroid, or by locally synthesized steroid, acting in a paracrine and/or autocrine fashion. The effects of cortisol in placenta must be due to glucocorticoid derived from the maternal or fetal compartment, since the placenta lacks the hydroxylases required for endogenous cortisol production. However, metabolism of cortisol by 11 beta-HSD-2 reduces the potency of this glucocorticoid in placental tissue. In chorion however, cortisol may be formed locally, from cortisone, in addition to its being derived from the maternal circulation and/or from the amniotic fluid. Our current studies do not allow us to delineate whether the effects of progesterone and cortisol on PGDH are exerted through the glucocorticoid receptor (GR) or progesterone receptor (PR) or both. It is possible that through pregnancy, PGDH activity is maintained by progesterone acting either through low levels of PR in membranes, or, more likely, acting through GR. At term, elevated levels of cortisol compete with and displace progesterone from GR, resulting in inhibition of PGDH transcription and activity. In this way, local withdrawal of progesterone action would be effected within human intrauterine tissues, without requiring changes in systemic, circulating progesterone

  19. Preparation of 15N-labeled L-alanine by coupling the alanine dehydrogenase and alcohol dehydrogenase reactions

    International Nuclear Information System (INIS)

    A simple enzymatic procedure for the preparation of L-[15N]alanine, one of the metabolically most active amino acids in all types of cells, is reported. The procedure is based on the coupling of two reactions, one catalyzed by bacterial alanine dehydrogenase, the second catalyzed by yeast alcohol dehydrogenase. An impediment in the use of this procedure could be the high cost of commercial AlaDH. However, the enzyme is widespread in the Bacillus species and partially purified samples, adequate preparative purposes, could be obtained relatively easily by chromatography on blue-Sepharose. (Auth.)

  20. Endothelial cell-initiated signaling promotes the survival and self-renewal of cancer stem cells

    OpenAIRE

    Krishnamurthy, Sudha; Dong, Zhihong; Vodopyanov, Dmitry; Imai, Atsushi; Helman, Joseph I.; Prince, Mark E.; Wicha, Max S.; Jacques E Nör

    2010-01-01

    Recent studies have demonstrated that cancer stem cells play an important role in the pathobiology of head and neck squamous cell carcinomas (HNSCC). However, little is known about functional interactions between head and neck cancer stem-like cells (CSC) and surrounding stromal cells. Here, we used Aldehyde Dehydrogenase activity and CD44 expression to sort putative stem cells from primary human HNSCC. Implantation of 1,000 CSC (ALDH+CD44+Lin−) led to tumors in 13 (out of 15) mice, while 10,...

  1. Phototheranostics of CD44-positive cell populations in triple negative breast cancer

    OpenAIRE

    Jiefu Jin; Balaji Krishnamachary; Yelena Mironchik; Hisataka Kobayashi; Bhujwalla, Zaver M.

    2016-01-01

    Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44high/CD24low, and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed...

  2. Interactions between migraine and tension-type headache and alcohol drinking, alcohol flushing, and hangover in Japanese

    OpenAIRE

    Yokoyama, Masako; Suzuki, Norihiro; Yokoyama, Tetsuji; Yokoyama, Akira; Funazu, Kazuo; Shimizu, Toshihiko; Shibata, Mamoru

    2012-01-01

    The aim of the study was to investigate associations between headache types and alcohol drinking, alcohol flushing, and hangover. Alcohol consumption is inhibited by the presence of inactive aldehyde dehydrogenase-2 (ALDH2) whose carriers are susceptible to alcohol flushing and hangovers. We conducted a cross-sectional study of the 2,577 subjects (men/women: 1,018/1,559) who reported having ever experienced headaches unrelated to common colds and alcohol hangovers among 5,408 (2,778/2,630) To...

  3. The Crystal Structure of Aquifex aeolicus Prephenate Dehydrogenase Reveals the Mode of Tyrosine Inhibition*

    OpenAIRE

    Sun, Warren; Shahinas, Dea; Bonvin, Julie; Hou, Wenjuan; Kimber, Matthew S.; Turnbull, Joanne; Christendat, Dinesh

    2009-01-01

    TyrA proteins belong to a family of dehydrogenases that are dedicated to l-tyrosine biosynthesis. The three TyrA subclasses are distinguished by their substrate specificities, namely the prephenate dehydrogenases, the arogenate dehydrogenases, and the cyclohexadienyl dehydrogenases, which utilize prephenate, l-arogenate, or both substrates, respectively. The molecular mechanism responsible for TyrA substrate selectivity and regulation is unknown. To further our underst...

  4. Cofactor engineering of Lactobacillus brevis alcohol dehydrogenase by computational design

    NARCIS (Netherlands)

    Machielsen, M.P.; Looger, L.L.; Raedts, J.G.J.; Dijkhuizen, S.; Hummel, W.; Henneman, H.G.; Daussmann, T.; Oost, van der J.

    2009-01-01

    The R-specific alcohol dehydrogenase from Lactobacillus brevis (Lb-ADH) catalyzes the enantioselective reduction of prochiral ketones to the corresponding secondary alcohols. It is stable and has broad substrate specificity. These features make this enzyme an attractive candidate for biotechnologica

  5. Purification and characterization of xylitol dehydrogenase from Fusarium oxysporum

    DEFF Research Database (Denmark)

    Panagiotou, Gianni; Kekos, D.; Macris, B.J.;

    2002-01-01

    An NAD(+)-dependent xylitol dehydrogenase (XDH) from Fusarium oxysporum, a key enzyme in the conversion of xylose to ethanol, was purified to homogeneity and characterised. It was homodimeric with a subunit of M-r 48 000, and pI 3.6. It was optimally active at 45degreesC and pH 9-10. It was fully...

  6. 21 CFR 862.1420 - Isocitric dehydrogenase test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Isocitric dehydrogenase test system. 862.1420 Section 862.1420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  7. 21 CFR 862.1440 - Lactate dehydrogenase test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lactate dehydrogenase test system. 862.1440 Section 862.1440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  8. 21 CFR 862.1380 - Hydroxybutyric dehydrogenase test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hydroxybutyric dehydrogenase test system. 862.1380 Section 862.1380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  9. Molecular cloning of gluconobacter oxydans DSM 2003 xylitol dehydrogenase gene

    Science.gov (United States)

    Sadeghi, H. Mir Mohammad; Ahmadi, R.; Aghaabdollahian, S.; Mofid, M.R.; Ghaemi, Y.; Abedi, D.

    2011-01-01

    Due to the widespread applications of xylitol dehydrogenase, an enzyme used for the production of xylitol, the present study was designed for the cloning of xylitol dehydrogenase gene from Glcunobacter oxydans DSM 2003. After extraction of genomic DNA from this bacterium, xylitol dehydrogenase gene was replicated using polymerase chain reaction (PCR). The amplified product was entered into pTZ57R cloning vector by T/A cloning method and transformation was performed by heat shocking of the E. coli XL1-blue competent cells. Following plasmid preparation, the cloned gene was digested out and ligated into the expression vector pET-22b(+). Electrophoresis of PCR product showed a 789 bp band. Recombinant plasmid (rpTZ57R) was then constructed. This plasmid was double digested with XhoI and EcoRI resulting in 800 bp and 2900 bp bands. The obtained insert was ligated into pET-22b(+) vector and its orientation was confirmed with XhoI and BamHI restriction enzymes. In conclusion, in the present study the recombinant expression vector containing xylitol dehydrogenase gene has been constructed and can be used for the production of this enzyme in high quantities. PMID:22110522

  10. Phosphorylation of formate dehydrogenase in potato tuber mitochondria

    DEFF Research Database (Denmark)

    Bykova, N.V.; Stensballe, A.; Egsgaard, H.;

    2003-01-01

    Two highly phosphorylated proteins were detected after two-dimensional (blue native/SDS-PAGE) gel electrophoretic separation of the matrix fraction isolated from potato tuber mitochondria. These two phosphoproteins were identified by mass spectrometry as formate dehydrogenase (FDH) and the E1alpha...

  11. Alcohol consumption, alcohol dehydrogenase 3 polymorphism, and colorectal adenomas

    NARCIS (Netherlands)

    Tiemersma, E.W.; Wark, P.A.; Ocké, M.C.; Bunschoten, A.; Otten, M.H.; Kok, F.J.; Kampman, E.

    2003-01-01

    Alcohol is a probable risk factor with regard to colorectal neoplasm and is metabolized to the carcinogen acetaldehyde by the genetically polymorphic alcohol dehydrogenase 3 (ADH3) enzyme. We evaluated whether the association between alcohol and colorectal adenomas is modified by ADH3 polymorphism.

  12. Toxicity of algal-derived aldehydes to two invertebrate species: Do heavy metal pollutants have a synergistic effect?

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Rebecca L. [School of Marine Science and Technology, University of Newcastle upon Tyne, Ridley Building, Claremont Road, Newcastle upon Tyne NE1 7RU (United Kingdom)]. E-mail: r.l.taylor@ncl.ac.uk; Caldwell, Gary S. [School of Marine Science and Technology, University of Newcastle upon Tyne, Ridley Building, Claremont Road, Newcastle upon Tyne NE1 7RU (United Kingdom); Bentley, Matthew G. [School of Marine Science and Technology, University of Newcastle upon Tyne, Ridley Building, Claremont Road, Newcastle upon Tyne NE1 7RU (United Kingdom)

    2005-08-15

    The recent discovery of the production of anti-proliferative aldehydes in a variety of microalgal species has lead to considerable investigation into the effects of these toxins on aquatic invertebrates. Studies have, however, rarely considered the impact pollutants may have on grazer responses to algal toxins. In this study, the acute toxicities of five aldehydes to the rotifer Brachionus plicatilis and nauplii of the brine shrimp Artemia salina are examined using immersion assays. In addition, the effect of a representative of these aldehydes in the presence of sub-lethal levels of heavy metals was examined. B. plicatilis generally showed greater sensitivity to the aldehydes than A. salina. The polyunsaturated 2-trans,4-trans-decadienal was the most toxic to both species having 24 h LD{sub 50} values of 7 and 20 {mu}M for B. plicatilis and A. salina, respectively. The remaining aldehydes had different orders of toxicity for the two species with a stronger relationship observed between mortality and aldehyde carbon-chain length for A. salina whereas B. plicatilis mortality showed a stronger dependence on the presence of carbon-carbon double bonds in the aldehydes. The presence of 1 {mu}M of copper sulphate in solutions of decadienal resulted in the reduction of the 24 h LD{sub 50} of decadienal by approximately a third for both species. 1 {mu}M of copper chloride in solutions of decadienal reduced the 24 h LD{sub 50} of decadienal to A. salina nauplii by approximately 11% and 1 {mu}M zinc sulphate caused a reduction of only 3%. Pre-exposure of the organisms to 1 {mu}M copper sulphate had no significant impact on their subsequent mortality in decadienal. The ecological implications and the possible mechanisms for the action of copper sulphate on the response of organisms to decadienal are discussed.

  13. Effects of aerobic training on pyruvate dehydrogenase and pyruvate dehydrogenase kinase in human skeletal muscle.

    Science.gov (United States)

    LeBlanc, Paul J; Peters, Sandra J; Tunstall, Rebecca J; Cameron-Smith, David; Heigenhauser, George J F

    2004-06-01

    This study examined the effects of short- and long-term aerobic training on the stable up-regulation of pyruvate dehydrogenase (PDH) and PDH kinase (PDK) in human skeletal muscle. We hypothesized that 8 weeks, but not 1 week, of aerobic training would increase total PDH (PDHt) and PDK activities compared to pretraining, and this would be detectable at the level of gene transcription (mRNA) and/or gene translation (protein). Resting muscle biopsies were taken before and after 1 and 8 weeks of aerobic cycle exercise training. PDHt and PDK activities, and their respective protein and mRNA expression, did not differ after 1 week of aerobic training. PDHt activity increased 31% after 8 weeks and this may be partially due to a 1.3-fold increase in PDH-E(1)alpha protein expression. PDK activity approximately doubled after 8 weeks of aerobic training and this was attributed to a 1.3-fold increase in PDK2 isoform protein expression. Similar to 1 week, no changes were observed at the mRNA level after 8 weeks of training. These findings suggest that aerobically trained human skeletal muscle has an increased maximal capacity to utilize carbohydrates, evident by increased PDHt, but increased metabolic control sensitivity to pyruvate through increased contribution of PDK2 to total PDK activity. PMID:15020699

  14. Blockade of Notch3 inhibits the stem-like property and is associated with ALDH1A1 and CD44 via autophagy in non-small lung cancer.

    Science.gov (United States)

    Ma, Yuanyuan; Li, Mingzhen; Si, Jiahui; Xiong, Ying; Lu, Fangliang; Zhang, Jianzhi; Zhang, Liyi; Zhang, Panpan; Yang, Yue

    2016-06-01

    Acquired resistance to standard chemotherapy causes treatment failure in patients with local advanced and advanced non-small lung cancer (NSCLC). Cancer stem cells (CSCs) are a small subpopulation within cancer that is thought to be resistant to conventional chemotherapy. The Notch pathway is one of the most intensively studied for putative therapeutic targets of CSCs in solid tumors. In our study, suppression of Notch3 decreased colony and sphere formation of stem-like property in lung cancer cells. In addition, Notch3 expression was demonstrated to be upregulated in the patients with chemoresistance and related to poor prognosis of NSCLC patients. Our results also showed that CSC markers ALDH1A1 and CD44 were highly expressed in NSCLC patients with chemoresistance and these two markers were positively correlated with Notch3 expression in lung cancer specimens from TCGA database. Furthermore, the lung cancer cells with drug resistance were shown to be associated with activation of autophagy. All the data support a crucial role of Notch3 in the increase of stem-like property in NSCLC cells that might be associated with upregulation of ALDH1A1 and CD44 and activation of autophagy. PMID:27035162

  15. Acyl-CoA Dehydrogenase 9 Is Required for the Biogenesis of Oxidative Phosphorylation Complex I

    NARCIS (Netherlands)

    J. Nouws; L. Nijtmans; S.M. Houten; M. Brand; M. Huynen; H. Venselaar; S. Hoefs; J. Gloerich; J. Kronick; T. Hutchin; P. Willems; R. Rodenburg; R. Wanders; L. van den Heuvel; J. Smeitink; R.O. Vogel

    2010-01-01

    Acyl-CoA dehydrogenase 9 (ACAD9) is a recently identified member of the acyl-CoA dehydrogenase family. It closely resembles very long-chain acyl-CoA dehydrogenase (VLCAD), involved in mitochondria! (3 oxidation of long-chain fatty acids. Contrary to its previously proposed involvement in fatty acid

  16. Integrated quantification and identification of aldehydes and ketones in biological samples.

    Science.gov (United States)

    Siegel, David; Meinema, Anne C; Permentier, Hjalmar; Hopfgartner, Gérard; Bischoff, Rainer

    2014-05-20

    The identification of unknown compounds remains to be a bottleneck of mass spectrometry (MS)-based metabolomics screening experiments. Here, we present a novel approach which facilitates the identification and quantification of analytes containing aldehyde and ketone groups in biological samples by adding chemical information to MS data. Our strategy is based on rapid autosampler-in-needle-derivatization with p-toluenesulfonylhydrazine (TSH). The resulting TSH-hydrazones are separated by ultrahigh-performance liquid chromatography (UHPLC) and detected by electrospray ionization-quadrupole-time-of-flight (ESI-QqTOF) mass spectrometry using a SWATH (Sequential Window Acquisition of all Theoretical Fragment-Ion Spectra) data-independent high-resolution mass spectrometry (HR-MS) approach. Derivatization makes small, poorly ionizable or retained analytes amenable to reversed phase chromatography and electrospray ionization in both polarities. Negatively charged TSH-hydrazone ions furthermore show a simple and predictable fragmentation pattern upon collision induced dissociation, which enables the chemo-selective screening for unknown aldehydes and ketones via a signature fragment ion (m/z 155.0172). By means of SWATH, targeted and nontargeted application scenarios of the suggested derivatization route are enabled in the frame of a single UHPLC-ESI-QqTOF-HR-MS workflow. The method's ability to simultaneously quantify and identify molecules containing aldehyde and ketone groups is demonstrated using 61 target analytes from various compound classes and a (13)C labeled yeast matrix. The identification of unknowns in biological samples is detailed using the example of indole-3-acetaldehyde. PMID:24745975

  17. Catalyst for Gas Phase Hydrogenation of Aldehydes Successfully Developed by Daqing Chemical Research Center

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ A national invention patent has been granted to the method for preparation of the Cu-Zn-Al system catalyst for gas phase hydrogenation of aldehydes developed by the Daqing Chemi-cal Research Center (DCRC) under the PetroChina Petro-chemical Research Institute. This technology is mainly ap-plied to the gas phase process for hydrogenation of butanal/crotonaldehyde to manufacture butanol/octanol and has brought about hundreds of million RMB of economic ben-efits since its application.

  18. Clean Synthesis in Water:Darzens Condensation Reaction of Aromatic Aldehydes with Phenacyl Chloride

    Institute of Scientific and Technical Information of China (English)

    史达清; 张姝; 庄启亚; 王香善; 屠树江; 胡宏纹

    2003-01-01

    The Darzens condensation reaction of aromatic aldehydes with phenacyl chloride proceeded very efficiently in a water suspension medium in the presence of triethylbenzylammonium chloride and only trans-2,3-epoxy-1,3-diaryl-1-propanones were formed which can be isolated simply by filtration.The structures of these compounds were confirmed by elemental analysis,IR and 1H NMR spectra.Therir configurations are in agreement with that of the same compounds reported in the literature.Compared to the classical Darzens condensation,this new method has the advantages of good yields,high stereoselectivity,low running cost inexpensive and environmentally benign procedure.

  19. Peptide Deravatives as New Chiral Ligands for Enantioselective Phenylacetylene Addition to Aldehydes

    Institute of Scientific and Technical Information of China (English)

    ZHOU,Yi-Feng; GAO,Yan-Feng; KANG,Yong-Feng; HAN,Zhi-Jian; YAN,Wen-Jin; NI,Ming; WANG,Rui

    2004-01-01

    @@ The asymmetric addition of alkynylzinc to aldehydes is an important method of synthesizing chiral propargyl alcohols, which are important precursors to many chiral organic compounds. Recently, many significant chiral ligands in this area have been disclosed.[1] Use of a short peptide as a catalyst would allow expansion beyond the (still uncharted) repertoire of single amino acids, while conserving the advantages of a small molecule catalyst. To the best of our knowledge,no results of peptide derivatives as chiral ligands in this reaction has been disclosed to date.[2] Herein, we report the initial results of peptide derivatives, which have been used directly as a chiral ligand in this reaction (Scheme 1).

  20. Aldehydes, ketones, and carboxylic acids formed radiolytically in aqueous solutions of cyanides and simple nitriles

    International Nuclear Information System (INIS)

    A systematic search for aldehydes, ketones, and carboxylic acids was carried out in aqueous solutions of HCN, NH4CN, CH3CN, and C2H4CN, that had received multikilogray doses of 60Co γ radiation. About 30 radiolytic products were identified, among them a large variety of dicarboxylic and tricarboxylic acids. Some of them might be of significant interest in molecular evolution studies of prebiotic processes. They originate in the free-radical-initiated chemical reactions where the additional oligomerization processes are particularly important. Most of the radiolytic products appear in both cyanides and nitriles and point to the importance of reactions involving the carbon-nitrogen triple bond