By G. Gordon Gibson PhD, Paul Skett Fil.dr. (auth.)
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Cholesterol esterase. 5'-Nucleotidase. Lipid peroxidase. liB- and 178-hydroxysteroid dehydrogenases. ENZYMOLOGY AND MOLECULAR MECHANISMS 37 metabolism reactions. Thus, drug metabolism reactions should not be considered in isolation, but rather as part of an integrated system. Based on information gained from studies on both intact microsomal membranes, cytsolic fractions and purified enzyme components, it is the purpose of this chapter to clarify, on a molecular level, many of the enzymecatalysed reactions of drug metabolism.
In fact, particular cytochrome P450s would have several different names for the same enzyme if isolated in different laboratories - clearly an unsatisfactory situation. However, with the advent of gene cloning and sequencing, and the application of molecular biology techniques to cytochrome P450 structure analysis, the 1980s witnessed an explosion in the isolation and sequencing of cDNAs encoding multiple forms of the haemoprotein. This rapid accumulation of fulllength cytochrome P450 amino acid sequences (predicted from open reading frames of the cognate eDNA nucleotide sequences) then allowed the development of a coherent nomenclature system which has now been universally accepted and uniquely identifies more than 200 different cytochrome P450s.
A. C. (1992) The human hepatic cytochromes P450 involved in drug metabolism. Crit. Rev. , 22 1-21. M. (1991) Unique properties of the enzymes of detoxification. Drug Metab. , 19 847-52. 1 Introduction As described in chapter 1, drugs and xenobiotics are transformed by a variety of pathways in two distinct stages. The phase I (or functionalisation) reactions serve to introduce a suitable functional group into the drug molecule, thereby changing the drug in most cases to a more polar form and hence more readily excretable.
Introduction to Drug Metabolism by G. Gordon Gibson PhD, Paul Skett Fil.dr. (auth.)