Slow acetylator

Author:Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 29.10.2020

Dieser Artikel auf Deutsch

Synonym(s)

slow acetylators

Requires free registration (medical professionals only)

Please login to access all articles, images, and functions.

Our content is available exclusively to medical professionals. If you have already registered, please login. If you haven't, you can register for free (medical professionals only).


Requires free registration (medical professionals only)

Please complete your registration to access all articles and images.

To gain access, you must complete your registration. You either haven't confirmed your e-mail address or we still need proof that you are a member of the medical profession.

Finish your registration now

DefinitionThis section has been translated automatically.

The detoxification of drugs and xenobiotics by acetylation in the human organism is catalysed by the N-acetyltransferases (NAT) NAT1 and NAT2. The acetylation phenotype of a human being is genetically determined.

Slow acetylation (opposite: fast acetylation) is the term used to describe persons who, due to their special enzyme equipment, can only slowly biotransform certain drugs (e.g. sulfonamides, nitrazepam, isoniazid) through acetylation. This applies to 40-70% of Europeans, 90% of North Africans and 10% of Japanese and Chinese.

For example, people who acetylate isoniazid quickly have a plasma concentration of only 1 μg/ml 6 hours after taking 9.8 mg of substance per kg body weight. Slow acetylators still have 4-5 times the level of isoniazid in plasma during the same period.

The phenotype of the "slow acetylator" (SA) is caused by homozygous or combined heterozygous variants in the coding region of the NAT2 gene. 4 variant alleles (NAT2*5a/b, *6a, *7a/b, *14a) are particularly common. NAT2-related adverse drug reactions (ADRs) lead to polyneuropathy or hypersensitivity to sulfonamides in "slow acetylators".

Also relevant is the acetylation behaviour in contact with specific carcinogens, primarily the aromatic compounds such as nitrobenzene, aniline, dinitrotoluene and amino compounds of benzene.

It is known that bladder cancer caused by the substances benzidine, 4-aminodiphenyl and 2-naphthylamine occurs significantly more frequently in slow acetylators. Gastric non-cardiac adenocarcinoma (-GNA-) also occurs more frequently in slow acetylators than in a control group.

LiteratureThis section has been translated automatically.

  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. Brocvielle H et al (2003) N-acetyltransferase 2 acetylation polymorphism: prevalence of slow acetylators does not differ between atopic dermatitis patients and healthy subjects. Skin Pharmacol Appl Skin Physiol 16:386-392.
  3. 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.
  4. 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.
  5. 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.
  6. Westphal GA et al (2000) N-acetyltransferase 1 and 2 polymorphisms in para-substituted arylamine-induced contact allergy. Br J Dermatol 142:1121-1127.

Authors

Last updated on: 29.10.2020