Format

Send to

Choose Destination
Arch Biochem Biophys. 2007 Aug 15;464(2):241-50. Epub 2007 May 11.

Human aldo-keto reductases: Function, gene regulation, and single nucleotide polymorphisms.

Author information

1
Center of Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania School of Medicine, 130 C John Morgan Bldg., 3620 Hamilton Walk, Philadelphia, PA 19104-6084, USA. penning@pharm.med.upenn.edu

Abstract

Aldo-keto reductases (AKRs) are a superfamily of NAD(P)H linked oxidoreductases that are generally monomeric 34-37kDa proteins present in all phyla. The superfamily consists of 15 families, which contains 151 members (www.med.upenn.edu/akr). Thirteen human AKRs exist that use endogenous substrates (sugar and lipid aldehydes, prostaglandins, retinals and steroid hormones), and in many instances they regulate nuclear receptor signaling. Exogenous substrates include metabolites implicated in chemical carcinogenesis: NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone), polycyclic aromatic hydrocarbon trans-dihydrodiols, and aflatoxin dialdehyde. Promoter analysis of the human genes identifies common elements involved in their regulation which include osmotic response elements, anti-oxidant response elements, xenobiotic response elements, AP-1 sites and steroid response elements. The human AKRs are highly polymorphic, and in some instances single nucleotide polymorphisms (SNPs) of high penetrance exist. This suggests that there will be inter-individual variation in endogenous and xenobiotic metabolism which in turn affect susceptibility to nuclear receptor signaling and chemical carcinogenesis.

PMID:
17537398
PMCID:
PMC2025677
DOI:
10.1016/j.abb.2007.04.024
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center