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Published on: March 20, 2018
Aldo-keto reductases and bioactivation/detoxication.
1Department of Pharmacology, Center of Excellence in Environmental Toxicology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Annual Review of Pharmacology and Toxicology
|September 15, 2006
Summary
Aldo-keto reductases (AKRs) are crucial enzymes that metabolize drugs and toxins. These stress-regulated enzymes play key roles in cellular defense and can either activate or detoxify harmful compounds.
Area of Science:
- Biochemistry
- Enzymology
- Molecular Biology
Background:
- Aldo-keto reductases (AKRs) are NAD(P)(H)-dependent oxidoreductases.
- They catalyze the reduction of aldehydes and ketones to alcohols.
- Human AKRs process diverse substrates, including drugs, carcinogens, and endogenous aldehydes.
Purpose of the Study:
- To elucidate the multifaceted roles of human AKRs in xenobiotic metabolism and cellular stress response.
- To highlight AKRs' involvement in drug metabolism, carcinogenesis, and detoxification pathways.
Main Methods:
- Bioinformatic analysis of AKR gene family.
- Enzymatic assays using various substrates.
- Studies on AKR expression under different stress conditions.
Main Results:
- Human AKRs exhibit broad substrate specificity, impacting drug efficacy and toxicity.
- AKRs are implicated in both the bioactivation and detoxification of carcinogens, including those from tobacco smoke.
- These enzymes are stress-regulated, responding to osmotic, electrophilic, and oxidative challenges.
Conclusions:
- AKRs are pivotal Phase I drug-metabolizing enzymes with significant implications in cancer and toxicology.
- Their dual role in bioactivation and detoxification underscores their complexity in cellular defense mechanisms.
- AKRs are critical components of the cellular stress response network.
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