Acetylation

A conjugation reaction carried out on drugs containing an amenable nitrogen atom by enzymes called N-acetyl transferases, predominantly N-acetyltransferase type 2 (NAT-2) in the liver and GI tract. An acetyl group is transferred from the carrier acetyl-CoA to a nitrogen on an amine, sulfonamide or hydrazine group. The acetylated metabolite is usually inactive, or has lost most of the activity of the parent drug.

Acetylation of the antibacterial sulfamethazine by NAT-2
Acetylation of the antibacterial sulfamethazine by NAT-2

N-Acetyltransferase enzymes are more usually involved in leukotriene biosynthesis but they can accept some drugs as substrates and acetylate them. The N-acetyl metabolites of some drugs – such as the sulfonamide antibacterials – may be less water-soluble than the parent drugs, and this can cause metabolites to precipitate in the kidneys as they are concentrated in the renal filtrate. This problem is more prevalent in so-called “fast acetylators”, a portion (around 50%) of the population that have high N-acetyl transferase activity. Due to a genetic polymorphism, the other 50% of the population are “slow acetylators” and precipitation of metabolites is less problematic.

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An ABC of PK/PD Copyright © 2023 by Dr. Andrew Holt is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, except where otherwise noted.

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