Transformation of Thebaine to Oripavine, Codeine, and Morphine by Rat Liver, Kidney, and Brain Microsomes

Thebaine, an intermediate of morphine biosynthesis in the poppy plant, Papaver somniferum, was transformed to oripavine, codeine, and morphine by rat liver, kidney, and brain microsomes in the presence of an NADPH-generating system. The formation of morphine, codeine, and oripavine was identified by...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1988-02, Vol.85 (4), p.1267-1271
Main Authors: Kodaira, Haruyoshi, Spector, Sydney
Format: Article
Language:English
Subjects:
Alkaloids
Animals
Bioconversions. Hemisynthesis
Biological and medical sciences
Biotechnology
Biotransformation
Brain - metabolism
Carbon Monoxide - pharmacology
Codeine - biosynthesis
Cytosol
Enzymes
Fundamental and applied biological sciences. Psychology
Kidney - metabolism
Kidneys
Liver
Liver microsomes
Male
Methods. Procedures. Technologies
Microsomes
Microsomes - metabolism
Microsomes, Liver - drug effects
Microsomes, Liver - metabolism
Morphine
Morphine - biosynthesis
NAD - metabolism
NADP - metabolism
Pyridines - pharmacology
Rats
Rats, Inbred Strains
Solvents
Thebaine - analogs & derivatives
Thebaine - biosynthesis
Thebaine - metabolism
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Summary:Thebaine, an intermediate of morphine biosynthesis in the poppy plant, Papaver somniferum, was transformed to oripavine, codeine, and morphine by rat liver, kidney, and brain microsomes in the presence of an NADPH-generating system. The formation of morphine, codeine, and oripavine was identified by a specific RIA, HPLC, and GCMS. Thebaine also gave rise to four other compounds, which for the moment are unidentified. NADH dramatically increased the formation of both codeine and morphine when used together with an NADPH-generating system, especially in liver microsomes. NADPH is essential in the formation of oripavine from thebaine and morphine from codeine, while NADH is critical in the conversion of thebaine to codeine and from oripavine to morphine. Carbon monoxide or SKF 525A inhibited the conversion, indicating a role of cytochrome P-450. These results provide evidence for the enzymatic in vitro conversion by mammalian tissues of thebaine to morphine. The pathway is similar to that which exists in plants.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.85.4.1267