By G. Gordon Gibson PhD, Paul Skett Fil.dr. (auth.)
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Extra resources for Introduction to Drug Metabolism
The metabolism of steroids is intimately linked to that of drugs as can be seen from the common developmental patterns and physiological control. Indeed, steroid biosynthesis is dependent on cytochrome P450 at many stages. This may be of the microsomal or the mitochondrial type of mixed-function oxidase (see chapter 2) depending on the reaction being studied. The importance of this enzyme is best illustrated by looking at the biosynthesis of steroids from cholesterol. 52). A specific form of cytochrome P450 has been isolated from the mitochondria of steroid-producing tissues that performs the above reaction.
S- Glutathione CL ~NO, (al c¢rN0 2 N02 + + H + Cl N0 2 H\. 45 Glutathione conjugation of (a) 2,4-dinitro-1-chlorobenzene and (b) esters of maleic acid. 46 The further metabolism of a glutathione conjugate. 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.
TIG 6 182-6. P. (1988) Mammalian cytochrome P450 Vol. 1 and 2, CRC Press, Boca Raton, Florida. P. (1989) Characterization of human microsomal P450 enzymes. Ann Rev. Pharmacal. , 29 241-64. P. (I 990) Enzymatic oxidation of xenobiotic chemicals. Biochem. Mole c. , 25 97. P. (1991) Reactions and significance of cytochrome P450 enzymes. J. Bioi. , 266 100 I 9-22. P. (1992) Human cytochrome P450 enzymes. , 50 1471-8. Ingelman-Sundberg, M. et at. (1990) Drug metabolising enzymes: Genetics, regulation and toxicology.
Introduction to Drug Metabolism by G. Gordon Gibson PhD, Paul Skett Fil.dr. (auth.)