Phase II Reactions: Acetylation Reactions

Acetylation is a crucial phase II biotransformation process involving the addition of an acetyl group to a substrate.

It is similar to α-amino acid conjugation. However, it utilizes exogenous amines as substrate. Endogenous acetyl CoA, derived from carbohydrate and fatty acid metabolism, acts as the acylating agent.

The nonmicrosomal enzyme N-acetyltransferase catalyzes this reaction.

Substrates susceptible to acetylation include functional groups like primary aliphatic  and aromatic amines, hydrazines, and sulfonamides. Apart from drugs, acetylation also plays a vital role in the metabolism of neurotransmitters and hormones.

This process can result in xenobiotic deactivation or the synthesis of active metabolites. Certain drugs like isoniazid and procainamide are predominantly metabolized through acetylation.

Acetylation polymorphism is a  genetic variation that affects the activity of  N-acetyltransferase in different people and can influence drug metabolism.

Notably, acetylation can potentially cause drug toxicity, exemplified by arylacetamide-induced liver damage.