N-acetyltransferases

Important enzyme group which catalyses the transfer of acetyl residues, among other things during the activation and detoxification of metabolites by N-acetylation, O-acetylation or N,O-acetylation. They are also important in phase II reactions in drug metabolism in the liver. Furthermore, a serotonin-specific N-acetyl transferase is of importance, which catalyses the conversion of serotonin into melatonin.

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

Basically, a 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 tuberculostat INH caused by the patient's acetylator status). The phenotype of the slow acetylator is caused by a mutation in the coding region of the NAT2 gene. 4 variant alleles are particularly common. Clinically, NAT2-related ADRs of the slow acetylator are manifested as peripheral neuropathy in INH therapy or as hypersensitivity in sulfonamides.

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 of contact allergies.

From 1 ml EDTA blood, the suspected diagnosis: drug intolerance (ICD-10 Code: T88.7) can be carried out in appropriate laboratories with the order Mutation search NAT2 gene by a sequence analysis.

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.
4. Kawakubo Y et al (1998) Properties of cutaneous acetyltransferase catalyzing N- and O-acetylation of carcinogenic arylamines and N-hydroxyarylamines. Biochem Pharmacol 37:265-270.
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.