Biotransformation flavin monooxygenase

Oxidations are the most common biotransformation reactions that occur with most drugs. There are several classes of enzymes that carry out these reactions cytochrome P450s, flavin monooxygenases, monoamine oxidases, xanthine oxidase, aldehyde oxidases, aldehyde dehydrogenases, and peroxidases. Typical reactions and substrate substructures for each of these classes of enzymes will be described. 

Schlenk D, DR Buhler (1991) Role of flavin-containing monooxygenase in the in vitro biotransformation of aldicarb in rainbow trout (Oncorhyncus mykiss). Xenobiotica 21 1583-1589. 

Phase I oxidation generally is described as the addition of an oxygen atom (e.g., as an hydroxyl moiety) to the parent molecule. Phase I oxidation is carried out by multiple enzyme pathways, including the various isoforms of the cytochrome P450 (CYP) family and the non-P450 biotransformation enzymes such as flavin-containing monooxygenase (FMO) and monamine oxidase (MAO). 

Oxidative biotransformations, which constitutes the major portion of Phase I reactions, can be catalyzed by either cytochrome P450s (CYP450) or nonmicrosomal enzymes such as flavin-containing monooxygenases (FMOs), monoamine oxidase (MAOs), alcohol dehydrogenase, and aldehyde dehydrogenase. As listed in Table 5.1,... 

Low et al. (2004) have proposed a model to explain thioacetamide-induced hepatotox-icity and cirrhosis in rat livers. The pathways of thioacetamide-induced liver fibrosis were found to be initiated by thioacetamide S-oxide derived from the biotransformation of thioacetamide by the microsomal flavin-adenine nucleotide containing monooxygenase and cytochrome P450 systems and involve oxidative stress and depletion of succinyl-CoA, thus affecting heme and iron metabolism. Karabay et al. (2005) observed such hepatic damage in rats with elevation of total nitrite level in livers and decrease in arginase activity. The authors have reported that nitrosative stress was essentially the critical factor in thioacetamide-induced hepatic failure in rats. 

Cashman JR. Monoamine oxidase and flavin-containing monooxygenases. In Guengerich FP, editor. Biotransformation, Vol. 3, Comprehensive Toxicology, first ed. Elsevier Science, Oxford 1997. p 69-96. 

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