Acetylation

Stable Identifier
R-HSA-156582
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser
N-acetyltransferases (NATs; EC 2.3.1.5) utilize acetyl Co-A in acetylation conjugation reactions. This is the preferred route of conjugating aromatic amines (R-NH2, converted to aromatic amides R-NH-COCH3) and hydrazines (R-NH-NH2, converted to R-NH-NH-COCH3). Aliphatic amines are not substrates for NAT. The basic reaction is

Acetyl-CoA + an arylamine = CoA + an N- acetylarylamine


NATs are cytosolic and in humans, 2 isoforms are expressed, NAT1 and NAT2. A third isoform, NATP, is a pseudogene and is not expressed. The NAT2 gene contains mutations that decrease NAT2 activity. This mutations was first seen as slow acetylation compared to the normal, fast acetylation of the antituberculosis drug isoniazid. Incidence of the slow acetylator phenotype is high in Middle Eastern populations (70%), average (50%) in Europeans, Americans and Australians and low in Asians (<25% in Chinese, Japanese and Koreans). N-acetylation and methylation pathways differ from other conjugation pathways in that they mask an amine with a nonionizable group so that the conjugates are less water soluble than the parent compound. However, certain N-acetlylations facilitate urinary excretion.
N-acetylation occurs in two sequential steps via a ping-pong Bi-Bi mechanism. In the first step, the acetyl group from acetyl-CoA is transferred to a cysteine residue in NAT, with consequent release of coenzyme-A. In the second step, the acetyl group is released from the acetylated NAT to the substrate, subsequently regenerating the enzyme.
Literature References
PubMed ID Title Journal Year
2340091 Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression

Blum, M, Grant, DM, Meyer, UA, Heim, M, McBride, W

DNA Cell Biol 1990
  Casarett and Doull's Toxicology 5th Edn

Parkinson, A

  1995
12052143 Arylamine N-acetyltransferases and drug response

Meisel, P

Pharmacogenomics 2002
1559981 Site-directed mutagenesis of recombinant human arylamine N-acetyltransferase expressed in Escherichia coli. Evidence for direct involvement of Cys68 in the catalytic mechanism of polymorphic human NAT2.

Grant, DM, Dupret, JM

J Biol Chem 1992
Participants
Participates
Event Information
Orthologous Events
Authored
Created
Cite Us!