4.4 Review

THE ALDO-KETO REDUCTASE SUPERFAMILY AND ITS ROLE IN DRUG METABOLISM AND DETOXIFICATION

Journal

DRUG METABOLISM REVIEWS
Volume 40, Issue 4, Pages 553-624

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/03602530802431439

Keywords

Aldo-keto reductase; AKR; Carbonyl reduction; Gene homology; Structural motif; alpha, beta-barrel; Detoxification; Pharmaceutical; Xenobiotic

Funding

  1. NIH [HL-544771, HL-59378, ES-11860, HL-089372]
  2. AHA [0865466D]
  3. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R21HL089372, R01HL059378, R01HL055477] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P01ES011860] Funding Source: NIH RePORTER

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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 (beta/alpha)(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.

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