ABSTRACT

The second major class of enzymes that serve to protect the organism from the potential toxicity of foreign compounds are the conjugating enzymes. In general, conjugation pathways involve the addition of a hydrophilic group such as glucuronic acid (see below) to a drug, and the mechanism involves an enzyme and a cofactor that is the source of this hydrophilic group. The cofactor usually contains a high-energy bond, such as a diphosphate, that facilitates the reaction. Conjugation usually adds a charge to the drug thus making the drug more polar and facilitating renal excretion; however, some conjugation pathways, in particular methylation and acetylation, do not increase the polarity of the substrate, but these two pathways do usually decrease pharmacological activity.