78 FR 39339 - Importer of Controlled Substances; Notice of Registration; SA INTL GMBH C/O., Sigma Aldrich Co., LLC

Science.gov (United States)

2013-07-01

... Methadone (9250) II Morphine (9300) II Thebaine (9333) II Opium, powdered (9639) II Levo-alphacetylmethadol... treaties, conventions, or protocols in effect on May 1, 1971, at this time. DEA has investigated SA INTL...

Somatic Embryogenesis, Rhizogenesis, and Morphinan Alkaloids Production in Two Species of Opium Poppy

Directory of Open Access Journals (Sweden)

My Abdelmajid Kassem

2001-01-01

Morphine was only detected in aerial parts of Papaver somniferum album. Codeine and thebaine were detected in the rhizogenous but no embryonic callus. These results suggest that root organogenesis is causally related to alkaloid biosynthesis.

Gene actions for yield and its attributes and their implications in the inheritance pattern over three generations in opium poppy (Papaver somniferum L.).

Science.gov (United States)

Mishra, Brij K; Mishra, R; Jena, S N; Shukla, Sudhir

2016-09-01

The gene actions for yield and its attributes and their inheritance pattern based on five parameter model have been explored in four single crosses (NBIHT-5 × NBIHT-6, NBIHT-5 × NBMHT-1, NBMHT-1 × NBIHT-6 and NBMHT-2 × NBMHT-1) obtained using thebaine rich pure lines of opium poppy (Papaver somniferum L.) for three consecutive generations. All the traits showed nonallelic mode of interaction, however, dominance effect (h) was more pronounced for all the traits except thebaine and papaverine. The dominance × dominance (l) effects were predominant over additive × additive (i) for all traits in all the four crosses except for papaverine. The seed and opium yield, and its contributing traits inherited quantitatively. The fixable gene effects (d) and (i) were lower in magnitude than nonfixable (h) and (l) gene effects. The estimates of heterosis were also higher in comparison to the respective parents which suggested preponderance of dominance gene action for controlling most of the traits. The phenotypic coefficient of variation was marginally higher than those of genotypic coefficient of variation for all the traits. The traits thebaine, narcotine, morphine and opium yield had high heritability coupled with high genetic advance. The leaf number, branches per plant and stem diameter showed positive correlation with opium and seed yields. The selection of plants having large number of leaves, branches and capsules with bigger size would be advantageous to enhance the yield potential.

78 FR 69130 - Importer of Controlled Substances; Notice of Application: Johnson Matthey, Inc.

Science.gov (United States)

2013-11-18

... Coca Leaves (9040) II Thebaine (9333) II Opium, raw (9600) II Noroxymorphone (9668) II Poppy Straw..., which fall under the authority of section 1002(a)(2)(B) of the Act (21 U.S.C. 952(a)(2)(B)) may, in the...

21 CFR 1300.01 - Definitions relating to controlled substances.

Science.gov (United States)

2010-04-01

... individual to alleviate adverse physiological or psychological effects incident to withdrawal from the...) Hydrocodone; (G) Hydromorphone; (H) Metopon; (I) Morphine; (J) Oxycodone; (K) Oxymorphone; (L) Thebaine; (M... depressant effect on the central nervous system, including its salts, isomers, and salts of isomers whenever...

Straightforward analytical method to determine opium alkaloids in poppy seeds and bakery products

NARCIS (Netherlands)

Lopez Sanchez, Patricia; Pereboom-de Fauw, Diana P.K.H.; Mulder, Patrick P.J.; Spanjer, Martien; Stoppelaar, de Joyce; Mol, Hans G.J.; Nijs, de Monique

2018-01-01

A straightforward method to determine the content of six opium alkaloids (morphine, codeine, thebaine, noscapine, papaverine and narceine) in poppy seeds and bakery products was developed and validated down to a limit of quantification (LOQ) of 0.1 mg/kg. The method was based on extraction with

77 FR 67397 - Manufacturer of Controlled Substances; Notice of Application; Johnson Matthey, Inc.

Science.gov (United States)

2012-11-09

...; Notice of Application; Johnson Matthey, Inc. Pursuant to Sec. 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on September 10, 2012, Johnson Matthey, Inc., Pharmaceuticals Materials... Thebaine (9333) II The company plans to manufacture the listed controlled substances in bulk for...

76 FR 25376 - Manufacturer of Controlled Substances; Notice of Registration

Science.gov (United States)

2011-05-04

... the public interest at this time. DEA has investigated Johnson Matthey Inc. to ensure that the company... February 3, 2011, 76 FR 6159, Johnson Matthey Inc., Pharmaceuticals Materials, 900 River Road, Conshohocken...) II Hydrocodone (9193) II Morphine (9300) II Thebaine (9333) II The company plans to manufacture the...

78 FR 69133 - Manufacturer of Controlled Substances; Notice of Application; Johnson Matthey, Inc.

Science.gov (United States)

2013-11-18

...; Notice of Application; Johnson Matthey, Inc. Pursuant to Sec. 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on September 5, 2013, Johnson Matthey, Inc., Pharmaceuticals Materials... Methadone (9250) II Methadone intermediate (9254) II Morphine (9300) II Thebaine (9333) II The company plans...

75 FR 64743 - Importer of Controlled Substances; Notice of Application

Science.gov (United States)

2010-10-20

... Phenylacetone (8501) II Coca Leaves (9040) II Thebaine (9333) II Opium, raw (9600) II Noroxymorphone (9668) II... re-registration to import crude opium, poppy straw, concentrate of poppy straw, and coca leaves. As... such basic classes of controlled substances listed in schedule I or II, which fall under the authority...

76 FR 77253 - Importer of Controlled Substances; Notice of Application

Science.gov (United States)

2011-12-12

... Schedule Coca Leaves (9040) II Thebaine (9333) II Opium, raw (9600) II Noroxymorphone (9668) II Poppy Straw...-registration to import crude opium, poppy straw, concentrate of poppy straw, and coca leaves. Comments and... substances listed in schedule I or II, which fall under the authority of section 1002(a)(2)(B) of the Act (21...

77 FR 70824 - Importer of Controlled Substances; Notice of Application; Johnson Matthey, Inc.

Science.gov (United States)

2012-11-27

... Coca Leaves (9040) II Thebaine (9333) II Opium, raw (9600) II Noroxymorphone (9668) II Poppy Straw...-registration to import crude opium, poppy straw, concentrate of poppy straw, and coca leaves. Comments and... substances listed in schedule I or II, which fall under the authority of section 1002(a)(2)(B) of the Act (21...

Determination of opium and strychnos alkaloids by radiometric titrations with potassium thallium(I) iodide reagent

International Nuclear Information System (INIS)

Rama Rao, V.V.; Singh, N.J.; Tandon, S.N.

1980-01-01

The titrations were carried out by the batch method in test tubes, using 204 Tl-labelled potassium thallium(I) iodide as precipitant for alkaloids such as codeine, morphine, narcotine, papaverine, thebaine, strychnine and brucine. Direct and reverse titrations were investigated including sensitivity and accuracy. Codeine and narcotine were determined in some pharmaceutical preparations such as codeine sulfate tablets, codopyrin tablets and coscopin syrup

Morphine biosynthesis in opium poppy involves two cell types: sieve elements and laticifers.

Science.gov (United States)

Onoyovwe, Akpevwe; Hagel, Jillian M; Chen, Xue; Khan, Morgan F; Schriemer, David C; Facchini, Peter J

2013-10-01

Immunofluorescence labeling and shotgun proteomics were used to establish the cell type-specific localization of morphine biosynthesis in opium poppy (Papaver somniferum). Polyclonal antibodies for each of six enzymes involved in converting (R)-reticuline to morphine detected corresponding antigens in sieve elements of the phloem, as described previously for all upstream enzymes transforming (S)-norcoclaurine to (S)-reticuline. Validated shotgun proteomics performed on whole-stem and latex total protein extracts generated 2031 and 830 distinct protein families, respectively. Proteins corresponding to nine morphine biosynthetic enzymes were represented in the whole stem, whereas only four of the final five pathway enzymes were detected in the latex. Salutaridine synthase was detected in the whole stem, but not in the latex subproteome. The final three enzymes converting thebaine to morphine were among the most abundant active latex proteins despite a limited occurrence in laticifers suggested by immunofluorescence labeling. Multiple charge isoforms of two key O-demethylases in the latex were revealed by two-dimensional immunoblot analysis. Salutaridine biosynthesis appears to occur only in sieve elements, whereas conversion of thebaine to morphine is predominant in adjacent laticifers, which contain morphine-rich latex. Complementary use of immunofluorescence labeling and shotgun proteomics has substantially resolved the cellular localization of morphine biosynthesis in opium poppy.

Nitroso Diels-Alder (NDA) Reaction as an Efficient Tool for the Functionalization of Diene-Containing Natural Products

Science.gov (United States)

Carosso, Serena; Miller, Marvin J.

2014-01-01

This review describes the use of nitroso Diels-Alder reactions for the functionalization of complex diene-containing natural products in order to generate libraries of compounds with potential biological activity. The application of this methodology to the structural modification of a series of natural products (thebaine, steroidal dienes, rapamycin, leucomycin, colchicine, isocolchicine and piperine) is discussed using relevant examples from the literature from 1973 onwards. The biological activity of the resulting compounds is also discussed. Additional comments are provided that evaluate the methodology as a useful tool in organic, bioorganic and medicinal chemistry. PMID:25119424

Rapid qualitative and quantitative analysis of opiates in extract of poppy head via FTIR and chemometrics: towards in-field sensors.

Science.gov (United States)

Turner, Nicholas W; Cauchi, Michael; Piletska, Elena V; Preston, Christopher; Piletsky, Sergey A

2009-07-15

Identification and quantification of the opiates morphine and thebaine has been achieved in three commercial poppy cultivars using FTIR-ATR spectroscopy, from a simple and rapid methanolic extraction, suitable for field analysis. The limits of detection were 0.13 mg/ml (0.013%, w/v) and 0.3 mg/ml (0.03%, w/v) respectively. The concentrations of opiates present were verified with HPLC-MS. The chemometrics has been used to identify specific "signature" peaks in the poppy IR spectra for characterisation of cultivar by its unique fingerprint offering a potential forensic application in opiate crop analysis.

Death in a legal poppy field in Spain.

Science.gov (United States)

Martínez, María Antonia; Ballesteros, Salomé; Almarza, Elena; Garijo, Joaquín

2016-08-01

Opium is a substance extracted from Papaver somniferum L. Opium latex contains morphine, codeine, and thebaine and non-analgesic alkaloids such as papaverine and noscapine. In Spain opium growing is allowed only for scientific or pharmaceutical purposes and harvest is supervised by the Spanish Health Ministry. This work describes a sudden fatality involving opium consumption in a legal poppy field. The toxicological and autopsy findings, previous disease, paraphernalia, and scenario are discussed in order to clarify cause and manner of death. A 32-year-old white caucasian male was found unresponsive in a legal poppy field in the South of Spain. The emergency medical services responded to the scene where he was pronounced dead. The friends explained that the deceased had presented with about 30min of convulsions; in spite of trying to keep his airway tract open they noted that "he stayed airless". According to them the victim suffered from epilepsy. Tools found beside his body consisted of plain wood sticks with a blade razor, a fabric handle, and paper. A comprehensive toxicological screening for abuse and psychoactive drugs was performed in the deceased samples. This included ethanol and volatile analysis by HS-GC-FID in peripheral blood and urine, enzyme immunoassay in urine by CEDIA, and a basic drug screening in all samples (including paraphernalia) by GC-MS using modes full scan for screening/confirmation and selected ion monitoring for quantitation. The peripheral blood, urine, vitreous, and gastric content contained the following concentrations of opiates expressed in mg/L (gastric content additionally also expressed in mg total): 0.10, 7.12, 0.23, and 14.80 (2.81mg total) of thebaine, 0.13, 4.50, 0.13, and 6.60 (1.25mg total) of morphine (free), 0.48, 0.88, 0.17, and 1.50 (0.28mg total) of codeine. These tree opiates were also detected in the tools (paraphernalia) used by the deceased for opium consumption. Other toxicological findings were metabolites of

A hybrid FIA/HPLC system incorporating monolithic column chromatography

International Nuclear Information System (INIS)

Adcock, Jacqui L.; Francis, Paul S.; Agg, Kent M.; Marshall, Graham D.; Barnett, Neil W.

2007-01-01

We have combined the generation of solvent gradients using milliGAT pumps, chromatographic separations with monolithic columns and chemiluminescence detection in an instrument manifold that approaches the automation and separation efficiency of HPLC, whilst maintaining the positive attributes of flow injection analysis (FIA), such as manifold versatility, speed of analysis and portability. As preliminary demonstrations of this hybrid FIA/HPLC system, we have determined six opiate alkaloids (morphine, pseudomorphine, codeine, oripavine, ethylmorphine and thebaine) and four biogenic amines (vanilmandelic acid, serotonin, 5-hydroxyindole-3-acetic acid and homovanillic acid) in human urine, using tris(2,2'-bipyridyl)ruthenium(III) and acidic potassium permanganate chemiluminescence detection

Differentiation of illicit drugs with THz time-domain spectroscopy

International Nuclear Information System (INIS)

Liu Guifeng; Ma Shihua; Ji Te; Zhao Hongwei; Wang Wenfeng

2010-01-01

The tera hertz time-domain spectroscopy (THz-TDS) was used for sensing and identifying illicit drugs. The absorption spectra of seven illicit drug samples(morphine and its hydrochloride, cocaine hydrochloride, codeine phosphate, papaverine hydrochloride, pethidine hydrochloride, and thebaine) were studied by THz-TDS at 0.3-2.0 THz at room temperature. The geometric structure and vibration frequencies of morphine were calculated by density functional theory. The four absorption features were dominated by intra-/inter-molecular collective or lattice vibration modes. Each illicit drug has a distinct signature in its THz spectra. The results indicate that the THz-TDS can be used to identify and discriminate illicit drugs by their characteristic fingerprints. (authors)

[Papaver bracteatum, influence of cold treatment and cloning on Thebaine content of the capsules.].

Science.gov (United States)

Bastart-Malsot, M; Paris, M

1982-05-01

A high heterogeneity of thébaïne yields is revealed in capsules of plants obtained from seeds cultivated in a phytotron. Clonage methods could be used to perform culture. Heterogeneity of plants hides influence of low temperature on thebaïne production. With clone this influence appears to be slight but appreciable.

Radiation Induced Treatment of Organic Pollutants

Energy Technology Data Exchange (ETDEWEB)

Ergun, E.; Öztürk, Ş.; Kantoğlu, Ö. [Turkish Atomic Energy Authority, Sarayköy Nuclear research and Training Center, Ankara (Turkey)

2012-07-01

In this period of the research, aerobic and anaerobic digestion, characterization of alkaloids present and radiolysis products formed after irradiation, under different conditions of ambient and additives, optimization of dose to achieve desired end characteristics for discharge of waste water were aimed. In this regard, unirradiated and irradiated wastewaters were subjected to aerobic and anaerobic digestions. Substrate removal efficiencies of unirradiated and irradiated wastewater with various initial COD values were determined with SBR aerobic digestion treatment method. On the other hand Fenton’s advanced oxidation treatment method was also applied for pre-treatment. BMP tests of anaerobic digestion were also completed. LC/MS studies were carried out on unirradiated and irradiated alkaloid standard solutions of morphine, codeine, thebaine, papaverine, and noscapine to determine the degradation mechanisms and byproducts. Dose optimization studies were completed and found to be a lower dose of 5 kGy rather than 40 kGy for ambient irradiation conditions. (author)

Radiation Induced Treatment of Organic Pollutants

International Nuclear Information System (INIS)

Ergun, E.; Öztürk, Ş.; Kantoğlu, Ö.

2012-01-01

In this period of the research, aerobic and anaerobic digestion, characterization of alkaloids present and radiolysis products formed after irradiation, under different conditions of ambient and additives, optimization of dose to achieve desired end characteristics for discharge of waste water were aimed. In this regard, unirradiated and irradiated wastewaters were subjected to aerobic and anaerobic digestions. Substrate removal efficiencies of unirradiated and irradiated wastewater with various initial COD values were determined with SBR aerobic digestion treatment method. On the other hand Fenton’s advanced oxidation treatment method was also applied for pre-treatment. BMP tests of anaerobic digestion were also completed. LC/MS studies were carried out on unirradiated and irradiated alkaloid standard solutions of morphine, codeine, thebaine, papaverine, and noscapine to determine the degradation mechanisms and byproducts. Dose optimization studies were completed and found to be a lower dose of 5 kGy rather than 40 kGy for ambient irradiation conditions. (author)

Evaluation of hydrophilic interaction liquid chromatography stationary phases for analysis of opium alkaloids.

Science.gov (United States)

Bagheri, Mohsen; Taheri, Mohammadreza; Farhadpour, Mohsen; Rezadoost, Hassan; Ghassempour, Alireza; Aboul-Enein, Hassan Y

2017-08-18

The separation of a mixture containing five major opium alkaloids, namely morphine, codeine, thebaine, noscapine and papaverine has been investigated in hydrophilic interaction liquid chromatography (HILIC) mode using five different stationary phases: bare silica, zwitterion, aminopropyl, diol and cyanopropyl. In order to propose the appropriate column for separation and purification, retention behaviors of the five natural opioids have been studied on mentioned HILIC stationary phases. The mechanism of separation in diverse HILIC media, based on the formation of water-rich layer on surface of the HILIC stationary phases and the physicochemical properties of opium alkaloids, such as pKa (acidic pK) and the octanol-water distribution coefficient (log Do/w) are discussed. Chromatographic responses including modified limit of detection LOD m , signal to noise ratio (S/N) m , and defined modified R Sm have considered for suggestion of the suitable column for quantitative/qualitative and preparative purposes. According to the obtained results, diol stationary phase is best suited for analytical chromatography, whereas bare silica and zwitterionic stationary phases are appropriate for preparative applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy.

Science.gov (United States)

Farrow, Scott C; Hagel, Jillian M; Beaudoin, Guillaume A W; Burns, Darcy C; Facchini, Peter J

2015-09-01

The gateway to morphine biosynthesis in opium poppy (Papaver somniferum) is the stereochemical inversion of (S)-reticuline since the enzyme yielding the first committed intermediate salutaridine is specific for (R)-reticuline. A fusion between a cytochrome P450 (CYP) and an aldo-keto reductase (AKR) catalyzes the S-to-R epimerization of reticuline via 1,2-dehydroreticuline. The reticuline epimerase (REPI) fusion was detected in opium poppy and in Papaver bracteatum, which accumulates thebaine. In contrast, orthologs encoding independent CYP and AKR enzymes catalyzing the respective synthesis and reduction of 1,2-dehydroreticuline were isolated from Papaver rhoeas, which does not accumulate morphinan alkaloids. An ancestral relationship between these enzymes is supported by a conservation of introns in the gene fusions and independent orthologs. Suppression of REPI transcripts using virus-induced gene silencing in opium poppy reduced levels of (R)-reticuline and morphinan alkaloids and increased the overall abundance of (S)-reticuline and its O-methylated derivatives. Discovery of REPI completes the isolation of genes responsible for known steps of morphine biosynthesis.

Literary investigation on the origin of poppy and other narcotics Research Articles

Directory of Open Access Journals (Sweden)

Lim Chung San

2009-06-01

Full Text Available Objectives : This study was performed to developing orally administered analgesics and locally injected pharmacopuncture analgesics like opioids. Methods : Literary investigation on the origin of poppy (Papaver somniferum L and other narcotics was conducted to examine the potential of developing orally administered analgesics and locally injected pharmacopuncture analgesics. Opium is a gum-like mass derived from air-dried white fluid of immature fruit of the poppy. Opium contains approximately 20 types of alkaloids including morphine, codeine, thebaine, papaverine and others. Natural opioids and synthetic alkaloid derivatives are the constituents of opioid analgesics and their effects and side-effects depend on the peculiarities of receptors. An extreme caution is required in the selection of proper dosage, proper analgesic types, and indications for successful pain management. Results and Discussion : With the enactment of "Narcotic control protocol", herbs such as cannibis and poppy are no longer available for use by Korean medicine doctors, and these doctors are faced with difficulty in managing severe pain in the clinical environment. A systematic consideration is inevitable for overcoming the limitation on these analgesics.

FREE RADICAL SCAVENGING CAPACITY OF PAPAVER SOMNIFERUM L. AND DETERMINATION OF PHARMACOLOGICALLY ACTIVE ALKALOIDS USING CAPILLARY ELECTROPHORESIS

Directory of Open Access Journals (Sweden)

Marián Valko

2012-02-01

Full Text Available The free radical generation is related to the oxidation process in biological systems as well as in foods. It was found that oxidation is affected by antioxidants that can act as radical scavengers. Objective of the present work was to study the free radical scavenging capacity of opium poppy (Papaver somniferum L. extract by using the DPPH test and to verify the suitability of the micellar electrokinetic capillary chromatography (MEKC technique for analytical assessment and determination of three major poppy alkaloids (thebaine, morphine and papaverine. Because of its generally high separation efficiency, the MEKC is successfully used for analytical evaluation of biologically active substances usually without special claims for sample preparation. The results of DPPH test have shown that poppy contains components capable of terminating free radicals. We have confirmed that nature of the solvent used for the electrophoretic medium in MEKC has a strong influence on the separation efficiency. In our experiments, the most effective solvent was mixture of water to acetonitrile (ratio 4:6.

Poppy Seed Consumption or Opiate Use: The Determination of Thebaine and Opiates of Abuse in Postmortem Fluids and Tissues

National Research Council Canada - National Science Library

Johnson, Robert D; Lewis, Russell J; Hattrup, Rachael A

2005-01-01

.... Therefore, the interpretation of positive opiate results must be viewed with caution. We have developed a simple method for the simultaneous determination of 8 opiate compounds from one extraction...

Dioxygenases Catalyze O-Demethylation and O,O-Demethylenation with Widespread Roles in Benzylisoquinoline Alkaloid Metabolism in Opium Poppy*

Science.gov (United States)

Farrow, Scott C.; Facchini, Peter J.

2013-01-01

In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy. PMID:23928311

Dioxygenases catalyze O-demethylation and O,O-demethylenation with widespread roles in benzylisoquinoline alkaloid metabolism in opium poppy.

Science.gov (United States)

Farrow, Scott C; Facchini, Peter J

2013-10-04

In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy.

Ageratum enation virus Infection Induces Programmed Cell Death and Alters Metabolite Biosynthesis in Papaver somniferum

Directory of Open Access Journals (Sweden)

Ashish Srivastava

2017-07-01

Full Text Available A previously unknown disease which causes severe vein thickening and inward leaf curl was observed in a number of opium poppy (Papaver somniferum L. plants. The sequence analysis of full-length viral genome and associated betasatellite reveals the occurrence of Ageratum enation virus (AEV and Ageratum leaf curl betasatellite (ALCB, respectively. Co-infiltration of cloned agroinfectious DNAs of AEV and ALCB induces the leaf curl and vein thickening symptoms as were observed naturally. Infectivity assay confirmed this complex as the cause of disease and also satisfied the Koch’s postulates. Comprehensive microscopic analysis of infiltrated plants reveals severe structural anomalies in leaf and stem tissues represented by unorganized cell architecture and vascular bundles. Moreover, the characteristic blebs and membranous vesicles formed due to the virus-induced disintegration of the plasma membrane and intracellular organelles were also present. An accelerated nuclear DNA fragmentation was observed by Comet assay and confirmed by TUNEL and Hoechst dye staining assays suggesting virus-induced programmed cell death. Virus-infection altered the biosynthesis of several important metabolites. The biosynthesis potential of morphine, thebaine, codeine, and papaverine alkaloids reduced significantly in infected plants except for noscapine whose biosynthesis was comparatively enhanced. The expression analysis of corresponding alkaloid pathway genes by real time-PCR corroborated well with the results of HPLC analysis for alkaloid perturbations. The changes in the metabolite and alkaloid contents affect the commercial value of the poppy plants.

A review of parameters and heuristics for guiding metabolic pathfinding.

Science.gov (United States)

Kim, Sarah M; Peña, Matthew I; Moll, Mark; Bennett, George N; Kavraki, Lydia E

2017-09-15

Recent developments in metabolic engineering have led to the successful biosynthesis of valuable products, such as the precursor of the antimalarial compound, artemisinin, and opioid precursor, thebaine. Synthesizing these traditionally plant-derived compounds in genetically modified yeast cells introduces the possibility of significantly reducing the total time and resources required for their production, and in turn, allows these valuable compounds to become cheaper and more readily available. Most biosynthesis pathways used in metabolic engineering applications have been discovered manually, requiring a tedious search of existing literature and metabolic databases. However, the recent rapid development of available metabolic information has enabled the development of automated approaches for identifying novel pathways. Computer-assisted pathfinding has the potential to save biochemists time in the initial discovery steps of metabolic engineering. In this paper, we review the parameters and heuristics used to guide the search in recent pathfinding algorithms. These parameters and heuristics capture information on the metabolic network structure, compound structures, reaction features, and organism-specificity of pathways. No one metabolic pathfinding algorithm or search parameter stands out as the best to use broadly for solving the pathfinding problem, as each method and parameter has its own strengths and shortcomings. As assisted pathfinding approaches continue to become more sophisticated, the development of better methods for visualizing pathway results and integrating these results into existing metabolic engineering practices is also important for encouraging wider use of these pathfinding methods.

Treatment of opium alkaloid containing wastewater in sequencing batch reactor (SBR)—Effect of gamma irradiation

Science.gov (United States)

Bural, Cavit B.; Demirer, Goksel N.; Kantoglu, Omer; Dilek, Filiz B.

2010-04-01

Aerobic biological treatment of opium alkaloid containing wastewater as well as the effect of gamma irradiation as pre-treatment was investigated. Biodegradability of raw wastewater was assessed in aerobic batch reactors and was found highly biodegradable (83-90% degradation). The effect of irradiation (40 and 140 kGy) on biodegradability was also evaluated in terms of BOD 5/COD values and results revealed that irradiation imparted no further enhancement in the biodegradability. Despite the highly biodegradable nature of wastewater, further experiments in sequencing batch reactors (SBR) revealed that the treatment operation was not possible due to sludge settleability problem observed beyond an influent COD value of 2000 mg dm -3. Possible reasons for this problem were investigated, and the high molecular weight, large size and aromatic structure of the organic pollutants present in wastewater was thought to contribute to poor settleability. Initial efforts to solve this problem by modifying the operational conditions, such as SRT reduction, failed. However, further operational modifications including addition of phosphate buffer cured the settleability problem and influent COD was increased up to 5000 mg dm -3. Significant COD removal efficiencies (>70%) were obtained in both SBRs fed with original and irradiated wastewaters (by 40 kGy). However, pre-irradiated wastewater provided complete thebain removal and a better settling sludge, which was thought due to degradation of complex structure by radiation application. Degradation of the structure was observed by GC/MS analyses and enhancement in filterability tests.

Treatment of opium alkaloid containing wastewater in sequencing batch reactor (SBR)-Effect of gamma irradiation

International Nuclear Information System (INIS)

Bural, Cavit B.; Demirer, Goksel N.; Kantoglu, Omer; Dilek, Filiz B.

2010-01-01

Aerobic biological treatment of opium alkaloid containing wastewater as well as the effect of gamma irradiation as pre-treatment was investigated. Biodegradability of raw wastewater was assessed in aerobic batch reactors and was found highly biodegradable (83-90% degradation). The effect of irradiation (40 and 140 kGy) on biodegradability was also evaluated in terms of BOD 5 /COD values and results revealed that irradiation imparted no further enhancement in the biodegradability. Despite the highly biodegradable nature of wastewater, further experiments in sequencing batch reactors (SBR) revealed that the treatment operation was not possible due to sludge settleability problem observed beyond an influent COD value of 2000 mg dm -3 . Possible reasons for this problem were investigated, and the high molecular weight, large size and aromatic structure of the organic pollutants present in wastewater was thought to contribute to poor settleability. Initial efforts to solve this problem by modifying the operational conditions, such as SRT reduction, failed. However, further operational modifications including addition of phosphate buffer cured the settleability problem and influent COD was increased up to 5000 mg dm -3 . Significant COD removal efficiencies (>70%) were obtained in both SBRs fed with original and irradiated wastewaters (by 40 kGy). However, pre-irradiated wastewater provided complete thebain removal and a better settling sludge, which was thought due to degradation of complex structure by radiation application. Degradation of the structure was observed by GC/MS analyses and enhancement in filterability tests.

Treatment of opium alkaloid containing wastewater in sequencing batch reactor (SBR)-Effect of gamma irradiation

Energy Technology Data Exchange (ETDEWEB)

Bural, Cavit B.; Demirer, Goksel N. [Middle East Technical University, Department of Environmental Engineering, 06531 Ankara (Turkey); Kantoglu, Omer [Turkish Atomic Energy Authority, Saraykoy Nuclear Research and Training Center, 06982, Kazan, Ankara (Turkey); Dilek, Filiz B., E-mail: fdilek@metu.edu.t [Middle East Technical University, Department of Environmental Engineering, 06531 Ankara (Turkey)

2010-04-15

Aerobic biological treatment of opium alkaloid containing wastewater as well as the effect of gamma irradiation as pre-treatment was investigated. Biodegradability of raw wastewater was assessed in aerobic batch reactors and was found highly biodegradable (83-90% degradation). The effect of irradiation (40 and 140 kGy) on biodegradability was also evaluated in terms of BOD{sub 5}/COD values and results revealed that irradiation imparted no further enhancement in the biodegradability. Despite the highly biodegradable nature of wastewater, further experiments in sequencing batch reactors (SBR) revealed that the treatment operation was not possible due to sludge settleability problem observed beyond an influent COD value of 2000 mg dm{sup -3}. Possible reasons for this problem were investigated, and the high molecular weight, large size and aromatic structure of the organic pollutants present in wastewater was thought to contribute to poor settleability. Initial efforts to solve this problem by modifying the operational conditions, such as SRT reduction, failed. However, further operational modifications including addition of phosphate buffer cured the settleability problem and influent COD was increased up to 5000 mg dm{sup -3}. Significant COD removal efficiencies (>70%) were obtained in both SBRs fed with original and irradiated wastewaters (by 40 kGy). However, pre-irradiated wastewater provided complete thebain removal and a better settling sludge, which was thought due to degradation of complex structure by radiation application. Degradation of the structure was observed by GC/MS analyses and enhancement in filterability tests.

Dwarf mutant of Papaver somniferum with high morphine content

International Nuclear Information System (INIS)

Chauhan, S.P.; Patra, N.K.; Srivastava, H.K.

1987-01-01

Opium poppy, Papaver somniferum L. is an important medicinal plant known for its morphine, codeine, and thebaine alkaloids. This Institute had earlier released two latex opium yielding poppy varieties, Shyama and Shweta, which are now cultivated by the farmers under the supervision of the Narcotic Department of the Government of India. However, both these varieties became susceptible to downy mildew (Peronospora arborescens). Lodging due to heavy capsule weight is another problem affecting latex yield. With these problems in mind, we undertook mutation breeding on the above mentioned two varieties employing gamma rays (5 kR, 15 kR, 20 kR) and EMS (0.2%, 0.4%, 0.6%) and combined mutagens (5 kR + 0.2% EMS, 5 kR + 0.4% EMS and 5 kR + 0.6% EMS). M 1 from the treated seeds (405 plants) was raised in winter 1984-85. M 2 generation of 13,500 plants (i.e. 270 M 1 progenies x 50 plants) was raised in winter 1985/86. A dwarf mutant with high morphine content was identified in M 2 from the variety Shweta treated with 5 kR + 0.4% EMS. The mutant differs by its dwarf stature, compact leaf arrangements, multilocular capsules, increased capsule number, and small capsule size. The mutant is under testing for its superior morphine production. It may be used as dwarf gene source in hybridization for improving lodging resistance. This mutant is a novel type, which was not available in our germplasm collection

Combination of electrochemistry with chemometrics to introduce an efficient analytical method for simultaneous quantification of five opium alkaloids in complex matrices.

Science.gov (United States)

Gholivand, Mohammad-Bagher; Jalalvand, Ali R; Goicoechea, Hector C; Gargallo, Raimundo; Skov, Thomas; Paimard, Giti

2015-01-01

For the first time, an analytical methodology based on differential pulse voltammetry (DPV) at a glassy carbon electrode (GCE) and integration of three efficient strategies including variable selection based on ant colony optimization (ACO), mathematical pre-processing selection by genetic algorithm (GA), and sample selection (SS) through a distance-based procedure to improve partial least squares-1 (PLS-1, ACO-GA-SS-PLS-1) multivariate calibration (MVC) for the simultaneous determination of five opium alkaloids including morphine (MOP), noscapine (NOP), thebaine (TEB), codeine (COD), and papaverine (PAP) was used and validated. The baselines of the DPV signals were modeled as a smooth curve, using P-splines, a combination of B-splines and a discrete roughness penalty. After subtraction of the baseline we got a signal with a two-component probability density. One component was for the peaks and it was approximated by a uniform distribution on the potential axis. The other component was for the observed noise around the baseline. Some sources of bi-linearity deviation for electrochemical data were discussed and analyzed. The lack of bi-linearity was tackled by potential shift correction using correlation optimized warping (COW) algorithm. The MVC model was developed as a quinternary calibration model in a blank human serum sample (drug-free) provided by a healthy volunteer to regard the presence of a strong matrix effect which may be caused by the possible interferents present in the serum, and it was validated and tested with two independent sets of analytes mixtures in the blank and actual human serum samples, respectively. Fortunately, the proposed methodology was successful in simultaneous determination of MOP, NOP, TEB, COD, and PAP in both blank and actual human serum samples and its results were satisfactory comparable to those obtained by applying the reference method based on high performance liquid chromatography-ultraviolet detection (HPLC-UV). Copyright