The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

Abstract

The aldo-keto reductase (AKR) superfamily comprises enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism, and detoxification. Substrates of AKRs include glucose, steroids, glycosylation end-products, lipid peroxidation products, and environmental pollutants. These proteins adopt a (β /α )₈ barrel structural motif interrupted by a number of extraneous loops and helixes that vary between proteins and bring structural identity to individual families. The human AKR family differs from the rodent families. Due to their broad substrate specificity, AKRs play an important role in the phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics.

Key Words:

• Aldo-keto reductase
• AKR
• Carbonyl reduction
• Gene homology
• Structural motif
• α, β-barrel
• Detoxification
• Pharmaceutical
• Xenobiotic

ACKNOWLEDGMENTS

This work was partly supported by NIH grants HL-544771, HL-59378, ES-11860 (to A.B.), and HL-089372 (to O.A.B.), as well as an AHA beginning grant in aid (0865466D) (to S.M.T.).

Notes

*Discussion of the gene structure of human AKRs and their homologies to rodents are based on the data contained in public accessible databases NCBI http://www.ncbi.nlm.nih.gov/ and Ensembl http://www.ensembl.org/. Murine and rat orthologs of human genes are identified based on the information of the Homologene database at NCBI.