Hydroxylation cytochrome P450 monooxygenase system

Among the reactions performed by the cytochrome P450 monooxygenase system, epox-idation, hydroxylation, N-dealkylation, O-dealkylation, desulfuration, and sulfoxidation are the most important with respect to pesticide metabolism ... 

SerizawaN, MatsuokaT (1991) A two component-type cytochrome P450 monooxygenase system in a prokaryote that catalyzes hydroxylation of ML-236B to pravastatin, a tissue-seleetive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Biochim BiophysActa 1084 35-40... 

H)2-D3 is a weak agonist and must be modified by hydroxylation at position Cj for full biologic activity. This is accomplished in mitochondria of the renal proximal convoluted tubule by a three-component monooxygenase reaction that requires NADPFl, Mg, molecular oxygen, and at least three enzymes (1) a flavoprotein, renal ferredoxin reductase (2) an iron sulfur protein, renal ferredoxin and (3) cytochrome P450. This system produces l,25(OH)2-D3, which is the most potent namrally occurring metabolite of vitamin D. 

Cell-free systems that convert ABA to PA have been obtained from liquid endosperm of Echinocystis lobata [109] and ABA-induced maize suspension cells [110]. The 8 -OH-ABA intermediate could be trapped by freezing short-term incubation mixtures, followed by lyophilization and acetylation [109]. The hydroxylating activity is localized to the microsomal fraction, requires O2 and NADPH [109,110], and is inhibited by CO [109], indicating that ABA 8 -hydroxylase is a cytochrome P450 monooxygenase. This is... 

Carbon monoxide inhibited the 6/3-. la-, and 16a-hydroxylation of testosterone by rat liver microsomes to different extents. A C0/02 ratio of 0.5 inhibited the la-, 6/i-, and 16a-hydroxylation reactions by 14%, 25%, and 36%, respectively, and the ratio of C0/02 needed for 50% inhibition of testosterone hydroxylation in the 16a-, 6/3-, and 7a-positions was 0.93, 1.54, and 2.36, respectively (36,48). Studies on the photochemical action spectrum revealed that CO inhibition of the three hydroxylation reactions was maximally reversed by monochromatic light at 450 nm, but there were differences in the shape of the photochemical reactivation spectra for the 6/3-, la-, and 16a-hydroxylation reactions (36,48). The data from our laboratory summarized above and at the First International Symposium on Microsomes and Drug Oxidation in 1968 pointed to multiple cytochromes P450 with different catalytic activities that were under separate regulatory control (36,45,46), and we indicated that the actual number of cytochromes that participate in the multiple hydroxylation reactions must await the solubilization and purification of the microsomal system (36). The use of different inducers of liver microsomal monooxygenases caused selective increases in the concentration of specific cytochromes P450 in fiver microsomes that greatly facilitated the isolation and purification of these hemoproteins. 

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