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Related Experiment Video

Updated: Jul 14, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

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

Trevor M Penning¹, Jason E Drury

¹Center 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

Archives of Biochemistry and Biophysics

|June 1, 2007

Summary

Aldo-keto reductases (AKRs) are crucial enzymes metabolizing endogenous and exogenous compounds. Genetic variations in human AKRs influence metabolism, affecting susceptibility to diseases like cancer.

Related Experiment Videos

Last Updated: Jul 14, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Area of Science:

Biochemistry
Molecular Biology
Genetics

Background:

Aldo-keto reductases (AKRs) are a large superfamily of oxidoreductases utilizing NAD(P)H.
They are monomeric proteins of 34-37kDa found across all phyla.
The AKR superfamily comprises 15 families and 151 members.

Purpose of the Study:

To investigate the role of human AKRs in metabolizing endogenous and exogenous substrates.
To explore the regulatory elements of human AKR genes.
To understand the implications of AKR genetic polymorphism on metabolism and disease susceptibility.

Main Methods:

Analysis of AKR substrate specificity, including endogenous compounds (sugars, lipids, prostaglandins, retinoids, steroids) and exogenous carcinogens (NNK, PAHs, aflatoxins).
Promoter analysis of human AKR genes to identify common regulatory elements.
Examination of human AKR gene polymorphism, including single nucleotide polymorphisms (SNPs).

Main Results:

Thirteen human AKRs metabolize various endogenous substrates, regulating nuclear receptor signaling.
AKRs also process exogenous substrates linked to chemical carcinogenesis.
Common regulatory elements like antioxidant and xenobiotic response elements are found in human AKR gene promoters.
High AKR polymorphism, including high-penetrance SNPs, exists in the human population.

Conclusions:

Human AKRs play a significant role in both endogenous and xenobiotic metabolism.
Genetic variations in AKRs can lead to inter-individual differences in metabolic pathways.
These variations may influence susceptibility to nuclear receptor signaling dysregulation and chemical carcinogenesis.