Role of drug-metabolizing enzymes in biotransformation of drugs

Biotransformation of drugs employs various enzymes along with some cofactors to convert into either active, inactive, or toxic metabolites. This conversion is important to facilitate the pharmacological action of drugs or for the excretion of polar toxic metabolites from the body. Phase I (reduction, oxidation, and hydrolysis) and phase II (conjugation) reactions are involved in the metabolism of drugs, xenobiotics, and exogenous and/or endogenous compounds. In phase I reactions, a diverse group of drugs biotransforming enzymes for oxidation of drugs include (cytochrome P450s, flavin monooxygenases, monoamine oxidases, alcohol and aldehyde dehydrogenases, aldehyde, and xanthine oxidases); the reducing enzymes that include (aldo-keto reductases, azo reductases, quinone reductases) and for hydrolysis, epoxide hydrolases, and esterases are generally involved. In phase II reactions, the conjugating enzymes are uridine diphospho glucuronosyltransferases, glutathione S-transferases, methyltransferase, N-acetyltransferase, and sulfotransferases that instigate glucuronidation, glutathione conjugation, methylation, acetylation, and sulfonation reactions.