Oxidative and Reductive Enzymes: Phase I Reactions

Both metabolism and excretion can be viewed as processes responsible for elimination of drug (parent and metabolite) from the body. Drug metabolism changes the chemical structure of a drug to produce a drug metabolite, which is frequently but not universally less pharmacologically active. Metabolism also renders the drug compound more water soluble and therefore more easily excreted. Drug metabolism reactions are carried out by enzyme systems that evolved over time to protect the body from exogenous chemicals. The enzyme systems for this purpose for the most part can be grouped into two categories: phase I oxidative or reductive enzymes and phase II conjugative enzymes. Enzymes within these categories exhibit some limited specificity in relation to the substrates acted upon; a given enzyme may interact with only a limited number of drugs. Some nonspecific hydrolytic enzymes, such as esterases and amidases, have not received much research attention. The focus of this discussion therefore is on phase I and phase II reactions and the enzymes that carry out these processes.