Synthesis of the skeleton of the morphine molecule by mammalian liver
The possibility that morphine could be synthesized in animals has long been considered and a pathway in mammalian brain analogous to that in the opium poppy has been proposed. Substances have been detected in mammalian brain that are recognized by antisera raised against morphine. Recently we report...
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| Veröffentlicht in: | Nature (London) 1987-12, Vol.330 (6149), p.674-677 |
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| creator | Weitz, Charles J Faull, Kym F Goldstein, Avram |
| description | The possibility that morphine could be synthesized in animals has long been considered and a pathway in mammalian brain analogous to that in the opium poppy has been proposed. Substances have been detected in mammalian brain that are recognized by antisera raised against morphine. Recently we reported the presence of three such immunoreactive substances in bovine hypothalamus and adrenal, and in rat brain, and the definitive identification of two of them by gas chromatography-mass spectrometry as morphine and codeine. Incorporation of a labelled precursor has demonstrated the biosynthesis of morphine in the opium poppy from tyrosine-derived units (see Fig. 1). Intramolecular coupling of reticuline to form salutaridine is the critical step that generates the morphine skeleton (morphinan) and the stereochemistry of the morphinan series. We now report the conversion in vivo and in vitro of reticuline to salutaridine by rat liver, but this conversion is not detectable in rat brain and bovine adrenal. This is the first direct demonstration of the synthesis of a morphinan in an animal tissue and also supports the hypothesis that morphine and codeine in brain and adrenal are of endogenous origin. |
| doi_str_mv | 10.1038/330674a0 |
| format | Article |
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Substances have been detected in mammalian brain that are recognized by antisera raised against morphine. Recently we reported the presence of three such immunoreactive substances in bovine hypothalamus and adrenal, and in rat brain, and the definitive identification of two of them by gas chromatography-mass spectrometry as morphine and codeine. Incorporation of a labelled precursor has demonstrated the biosynthesis of morphine in the opium poppy from tyrosine-derived units (see Fig. 1). Intramolecular coupling of reticuline to form salutaridine is the critical step that generates the morphine skeleton (morphinan) and the stereochemistry of the morphinan series. We now report the conversion in vivo and in vitro of reticuline to salutaridine by rat liver, but this conversion is not detectable in rat brain and bovine adrenal. This is the first direct demonstration of the synthesis of a morphinan in an animal tissue and also supports the hypothesis that morphine and codeine in brain and adrenal are of endogenous origin.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/330674a0</identifier><identifier>PMID: 3683586</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Adrenal Glands - metabolism ; Alkaloids - metabolism ; Analgesics ; Animal tissues ; Animals ; Benzylisoquinolines ; Biochemistry ; Biological and medical sciences ; Biosynthesis ; Brain ; Brain - metabolism ; Cattle ; Cellular biology ; Chromatography, High Pressure Liquid ; Gas chromatography ; Gas Chromatography-Mass Spectrometry ; Isoquinolines ; Liver - metabolism ; Mammals ; Mass spectrometry ; Medical sciences ; Morphinans - biosynthesis ; Morphine - biosynthesis ; Neurological disorders ; Neuropharmacology ; Pharmacology. Drug treatments ; Rats</subject><ispartof>Nature (London), 1987-12, Vol.330 (6149), p.674-677</ispartof><rights>1988 INIST-CNRS</rights><rights>Copyright Macmillan Journals Ltd. Dec 17, 1987</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-813d0ebf42fd0f0a4eeccfcf0bd1ba824b54126e3a017a03c7617fb908992d193</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7502079$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3683586$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Weitz, Charles J</creatorcontrib><creatorcontrib>Faull, Kym F</creatorcontrib><creatorcontrib>Goldstein, Avram</creatorcontrib><title>Synthesis of the skeleton of the morphine molecule by mammalian liver</title><title>Nature (London)</title><addtitle>Nature</addtitle><description>The possibility that morphine could be synthesized in animals has long been considered and a pathway in mammalian brain analogous to that in the opium poppy has been proposed. Substances have been detected in mammalian brain that are recognized by antisera raised against morphine. Recently we reported the presence of three such immunoreactive substances in bovine hypothalamus and adrenal, and in rat brain, and the definitive identification of two of them by gas chromatography-mass spectrometry as morphine and codeine. Incorporation of a labelled precursor has demonstrated the biosynthesis of morphine in the opium poppy from tyrosine-derived units (see Fig. 1). Intramolecular coupling of reticuline to form salutaridine is the critical step that generates the morphine skeleton (morphinan) and the stereochemistry of the morphinan series. We now report the conversion in vivo and in vitro of reticuline to salutaridine by rat liver, but this conversion is not detectable in rat brain and bovine adrenal. This is the first direct demonstration of the synthesis of a morphinan in an animal tissue and also supports the hypothesis that morphine and codeine in brain and adrenal are of endogenous origin.</description><subject>Adrenal Glands - metabolism</subject><subject>Alkaloids - metabolism</subject><subject>Analgesics</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Benzylisoquinolines</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Biosynthesis</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>Cattle</subject><subject>Cellular biology</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Gas chromatography</subject><subject>Gas Chromatography-Mass Spectrometry</subject><subject>Isoquinolines</subject><subject>Liver - metabolism</subject><subject>Mammals</subject><subject>Mass spectrometry</subject><subject>Medical sciences</subject><subject>Morphinans - biosynthesis</subject><subject>Morphine - biosynthesis</subject><subject>Neurological disorders</subject><subject>Neuropharmacology</subject><subject>Pharmacology. 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Substances have been detected in mammalian brain that are recognized by antisera raised against morphine. Recently we reported the presence of three such immunoreactive substances in bovine hypothalamus and adrenal, and in rat brain, and the definitive identification of two of them by gas chromatography-mass spectrometry as morphine and codeine. Incorporation of a labelled precursor has demonstrated the biosynthesis of morphine in the opium poppy from tyrosine-derived units (see Fig. 1). Intramolecular coupling of reticuline to form salutaridine is the critical step that generates the morphine skeleton (morphinan) and the stereochemistry of the morphinan series. We now report the conversion in vivo and in vitro of reticuline to salutaridine by rat liver, but this conversion is not detectable in rat brain and bovine adrenal. This is the first direct demonstration of the synthesis of a morphinan in an animal tissue and also supports the hypothesis that morphine and codeine in brain and adrenal are of endogenous origin.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>3683586</pmid><doi>10.1038/330674a0</doi><tpages>4</tpages></addata></record> |
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| ispartof | Nature (London), 1987-12, Vol.330 (6149), p.674-677 |
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| subjects | Adrenal Glands - metabolism Alkaloids - metabolism Analgesics Animal tissues Animals Benzylisoquinolines Biochemistry Biological and medical sciences Biosynthesis Brain Brain - metabolism Cattle Cellular biology Chromatography, High Pressure Liquid Gas chromatography Gas Chromatography-Mass Spectrometry Isoquinolines Liver - metabolism Mammals Mass spectrometry Medical sciences Morphinans - biosynthesis Morphine - biosynthesis Neurological disorders Neuropharmacology Pharmacology. Drug treatments Rats |
| title | Synthesis of the skeleton of the morphine molecule by mammalian liver |
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