Cytochrome P450 monooxygenase systems

High dietary carbohydrate levels in the rat tend to have much the same effect as low dietary protein, decreasing such activities as aminopyrine A -demelhylase, pentobarbital hydroxy lation, and / -nitrobenzoic acid reduction along with a concomitant decrease in the enzymes of the cytochrome P450 monooxygenase system. Because rats tend to regulate total caloric intake, this may actually reflect low-protein intake. 

Figure 9.1 Nutritional requirements with potential effects on the cytochrome P450 monooxygenase system (From W. E. Donaldeson Nutritional factors, in Introduction to Biochemical Toxicology, 3rd ed., E. Hodgson and R. C. Smart, Wiley, 2001.)...

The induction of liver enzymes has been demonstrated in many species, including humans, and probably represents a homeostatic, defense mechanism. Induction usually requires multiple exposures to the inducing agent over a period of several days, the time required for the synthesis of new protein. Enzymes induced include the cytochrome P450 monooxygenase system glucuronyltransferase the microsomal ethanol oxidative system and the steroid-metabolizing system. 

Fourth, certain segments of the nephron have a capacity for metabolic bioactivation. For example, the proximal and distal tubules contain isozymes of the cytochrome P450 monooxygenase system that may mediate intrarenal bioactivation of several protoxicants. Additionally, prostaglandin synthetase activity in medullary and papillary interstitial cells may be involved in cooxidation of protoxicants, resulting in selective papillary injury. 

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 ... 

Kupfer, D. (1982). Endogenous substrates of monooxygenases Fatty acids and prostaglandins. In J.B. Schenkman and D. Kupfer (eds). Hepatic Cytochrome P450 Monooxygenase System. Pergamon Press, Elmsford, NY, pp. 157-190. 

Backes WL, Canady WJ (1982) Methods for the evaluation of hydrophobic substrate binding to cytochrome P450. In Schenkman JB, Kupfer D (eds) Hepatic cytochrome P450 monooxygenase system. Pergamon Press, Elmsford, pp 787-812 (Int. Encyclopedia. Pharmacol. Therap., Section 108)... 

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... 

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