Phase II Reactions: Sulfation and Conjugation with α-Amino Acids

Sulfation, a phase II biotransformation reaction, involves the addition of a polar sulfate group to a drug.

The process is catalyzed by nonmicrosomal sulfotransferases and involves PAPS coenzyme activation, sulfate group transfer to the substrate, and sulfated metabolite generation.

Drugs containing phenols, alcohols, aromatic amines, and amides like acetaminophen, minoxidil, and morphine undergo sulfation.

Sulfate conjugates can be pharmacologically active, potentially causing tissue damage or carcinogenesis.

α-amino acid conjugation involves a drug linking to an α-amino acid like glycine or glutamine.

Acyltransferases catalyze this reaction by transferring the α-amino acid to the drug substrate.

The process comprises activating the carboxylic acid substrate, followed by acylation of the α-amino acid by the acyl CoA, catalyzed by N-acyltransferase, forming the conjugated metabolite.

Drugs with aliphatic or aromatic carboxylic acids, such as valproic and salicylic acids, undergo this conjugation.