Current Drug Metabolism

Michael Sinz
Bristol Myers Squibb
Wallingford, CT
USA

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Effect of Environmental Substances on the Activity of Arylamine N-Acetyltransferases

Author(s): Fernando Rodrigues-Lima, Julien Dairou and Jean-Marie Dupret

Affiliation: EA 1553, Universite Paris Diderot-Paris 7, 2 place Jussieu, 75005 Paris, France.

Keywords: N-acetyltransferases, xenobiotics, catalytic mechanism, covalent modifications, inhibition

Abstract:

Arylamine N-acetyltransferases (NAT) are xenobiotic-metabolizing enzymes responsible for the acetylation of many aromatic arylamine and heterocyclic amines, thereby playing an important role in both detoxification and activation of numerous drugs and carcinogens. Two closely related isoforms (NAT1 and NAT2) have been described in humans. NAT2 is mainly expressed in liver and gut, whereas NAT1 is found in a wide range of tissues. Interindividual variations in NAT genes have been shown to be a potential source of pharmacological and/or pathological susceptibility. In addition, there is now evidence that non genetic factors, such as substratedependent inhibition, drug interactions or cellular redox conditions may also contribute to NAT activity. The recent findings reviewed here provide possible mechanisms by which these environmental determinants may affect NAT activity. Interestingly, these data could contribute to the development of selective NAT inhibitors for the treatment of cancer and microbial diseases.

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Article Details

VOLUME: 9
ISSUE: 6
Page: [505 - 509]
Pages: 5
DOI: 10.2174/138920008784892092