ABSTRACT
This chapter deals briefly with xenobiotic metabolism and involves the major enzyme systems. It discusses in detail how these enzyme systems are perturbed by diabetes mellitus. Hundreds of chemicals have been linked to human disease, either following strong epidemiological evidence or extrapolation of experimental evidence obtained in animals. Drugs such as tienilic acid, dihydralazine, and halothane are metabolically converted by the cytochrome P450–dependent mixed-function oxidases to metabolites that bind covalently to proteins to generate neoantigens resulting in the production of autoantibodies. A number of enzyme systems contribute to the Phase I metabolism of chemicals, both activation and deactivation, including the cytochrome P450–dependent mixed-function oxidases, flavin monooxygenases, and the prostaglandin synthases. The cytochrome P450–dependent mixed-function oxidases are by far the most important enzyme system in the metabolism of xenobiotics. The expression of the cytochrome P450 proteins, whose primary function is the metabolism of endogenous substrates, in Insulin-Dependent Diabetes Mellitus (IDDM) has received very little attention.
