Skip to main content

Structure and Regulation of the Drug-Metabolizing Enzymes Arylamine N-acetyltransferases

Buy Article:

$63.00 plus tax (Refund Policy)

Abstract:

Arylamine N-acetyltransferases (NAT) are xenobiotic-metabolizing enzymes responsible for Nacetylation of many arylamines. They are also important for O-acetylation of N-hydroxylated heterocyclic amines. These enzymes play thus an important role in the detoxification and activation of numerous therapeutic drugs and carcinogens. Two closely related polymorphic isoforms (NAT1 and NAT2) have been described in humans and interindividual variations in NAT genes have been shown to be a potential source of adverse drug reaction. In addition, NAT1 and / or NAT2 phenotypes may modulate the risk of certain cancers in people exposed to aromatic amine carcinogens. Recent advances on the regulation of human NAT1 activity has shown that hydroxylamine and / or nitroso intermediates of NAT1 substrates inhibit the enzyme through direct irreversible interaction with its catalytic cysteine residue. Oxidative molecules such as hydrogen peroxide, Snitrosothiols and peroxynitrite have also been shown to inactivate reversibly or irreversibly the enzyme in a similar manner. In this review, after summarizing the general background on human NAT enzymes, we focus on the recent developments on the regulation of the activity of these drug-metabolizing enzymes by substrateintermediates and by oxidant molecules. The recent findings reviewed here provide possible mechanisms by which these non genetic determinants inhibit NAT1 activity and thereby may affect drug efficacy / toxicity.

Keywords: catalytic mechanisms; covalent modifications; n-acetyltransferases; oxidative stress; polymorphism; splice variants; xenobiotics

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867053363289

Affiliations: CNRS-UMR7000, Faculte de Medecine Pitie-Salpetriere, 105 bd de l'Hopital, 75013 Paris, France.

Publication date: February 1, 2005

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
ben/cmc/2005/00000012/00000003/art00005
dcterms_title,dcterms_description,pub_keyword
6
5
20
40
5

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more