Reactions of Acetylation

The factor involved in the acetylation reaction is acetyl-coenzyme A (50, Figure 17; R = COCH3; acetyl-CoA). The acetyl moiety is in activated form, being bound to CoA by a thioester bridge of increased reactivity compared to an oxoester. This endocon is transferred to a nucleophilic function in the substrate, namely an amino, hydroxy, or thiol group. As discussed below, weak amino groups are by far the best targets of acetylation in xenobiotic substrates. Various enzymes are known to catalyze acetylation reactions:

• arylamine N-acetyltransferase (arylamine acetylase; EC; NAT) is the major enzyme system involved in xenobiotic acetylation; two enzymes have been characterized in humans, namely NAT1 and the highly variable NAT292-94;

• aromatic-hydroxylamine O-acetyltransferase (EC and N-hydroxyarylamine O-acetyltransferase (EC are also involved in the acetylation of aromatic amines and hydroxylamines (see below); and

• other acetyltransferases include diamine N-acetyltransferase (putrescine acetyltransferase; EC and aralkylamine N-acetyltransferase (serotonin acetyltransferase; EC, but their involvement in xenobiotic metabolism does not appear to be sufficiently characterized.

Endocon Coenzyme Substrat Conjugaison







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