By G. Gordon Gibson PhD, Paul Skett Fil.dr. (auth.)
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Extra info for Introduction to Drug Metabolism
The tripeptide glutathione (Gly-Cys-Glu), once attached to the acceptor molecule, can be attacked by a glutamyltranspeptidase, which removes the glutamate, and a peptidase, which removes the glycine to yield the cysteine conjugate of the xenobiotic. These enzymes are found in the liver and kidney cytosol. N-Acetylation of the cysteine conjugate can then occur via the normal N-acetylation pathway described above to yield the N-acetylcysteine conjugate or mercapturic acid. CH. CO. 47 The phase I and II metabolism of naphthalene.
Physiol. , 69 537-49. E. and Levin, W. (1990) Purification and characterisation of hepatic microsomal cytochrome P450. Pharmacal. , 45 153-239. Soucek, P. and Gut, I. (1992) Cytochromes P450 in rats. Structures, functions, properties and relevant human forms. Xenobiotica, 22 83-103. Takemori, S. and Kominami, S. (1984) The role of cytochrome P450 in adrenal steroidogenesis. TIPS, 9 393-6. R. and Burchell, B. (1990) UDP-glucuronosyltransferases, a family of detoxifying enzymes. TIPS, 11 276--9. Testa, B.
These steps involve putative electron rearrangement, introduction of the second electron and subsequent oxygen insertion and product release. The precise oxidation states of iron and oxygen in these intermediates are not precisely known. 12), and possibly also derived from cytochrome b5 , although the precise role of cytochrome b 5 in cytochrome P450 catalysed drug oxidations remains the subject of much ENZYMOLOGY AND MOLECULAR MECHANISMS FAD/ FMNH2 (from step 2) 49 FAD/ FMNH" ~NADPHH+ f--NADP+ FADH2 I FMNH" ~ FADH.