N-acetyltransferases

Important group of enzymes that catalyze the transfer of acetyl residues, e.g. in the activation and detoxification of metabolites by N-acetylation, O-acetylation or N,O-acetylation. Among other things, they are important in phase II reactions during drug metabolization in the liver. Furthermore, a serotonin-specific N-acetyl transferase is important, which catalyzes the conversion of serotonin into melatonin.

N-acetyl transferases are of great importance for the detoxification of certain pharmaceuticals (e.g. INH, sulfonamides, various carcinogenic hydrocarbons) (see slow acetylators below).

A basic distinction is made between the phenotype of the "fast" (RA), the "slow" (SA) and the "intermediate" (IA) acetylator (initial observation due to differences in the metabolism of the tuberculostatic drug INH caused by the acetylator status of the patient). The "slow acetylator" phenotype is caused by a mutation in the coding region of the NAT2 gene. 4 variant alleles are particularly common. Clinically, NAT2-related ADRs in the "slow acetylator" manifest as peripheral neuropathy during INH therapy or as hypersensitivity to sulfonamides. Drug-induced lupus erythematosus (DI-LE) is also associated with a slow acetylator type.

The prevalence of the variant NAT2 alleles varies: in Europe about 40-70%, in North Africa about 90% of the population belong to the "slow acetylators".

Certain polymorphisms of the N-acetyltransferase gene(NAT1 or NAT2) lead to a higher tendency to contact allergies.

A suspected diagnosis of drug intolerance (ICD-10 code: T88.7) can be made from 1 ml of EDTA blood in appropriate laboratories by means of a sequence analysis with the order "NAT2 gene mutation search".

1. Bluhm RE et al (1999) Development of dapsone toxicity in patients with inflammatory dermatoses: activity of acetylation and hydroxylation of dapsone as risk factors. Clin Pharmacol Ther 65:598-605.
2. Chang CH et al (2016) N-acetyltransferase 2 (NAT2) genetic variation and the susceptibility to noncardiac gastric adenocarcinoma in Taiwan. J Chin Med Assoc 79:105-110.
3. Hengstler JG et al (1998) Polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. Recent Results Cancer Res 154:47-85.
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5. Westphal GA et al (2000) N-acetyltransferase 1 and 2 polymorphisms in para-substituted arylamine-induced contact allergy. Br J Dermatol 142:1121-1127.