Human Aflatoxin B1 aldehyde reductase member 3

Aflatoxin B1 is one of the most potent hepatocarcinogens known, and occurs as a toxic metabolite produced under conditions of high heat and humidity by fungal molds of the genus Aspergillus, growing on agricultural crops such as peanuts or corn.
The combined effects of this reactive fungal metabolite and the high occurrence of hepatitis virus infection lead to the extremely elevated incidence of hepatocellular cancer especially in Asia and Africa.

The carcinogenic effects are due to bioactivation to highly reactive species and ultimately lead to DNA adducts and lesions.
In humans, competing inactivating pathways include reduction of an intermediate Aflatoxin dialdehyde to the dialcohol product by human aldo-keto reductases.
Several members of the aldo-keto reductase (AKR) family, specifically members of the AKR7 subfamily, are involved in the detoxification and metabolism of a variety of exogenous aldehydes and ketones, such as aflatoxin dialdehyde.
The human isozymes AKR7A3 and AKR7A2 share 88% sequence identities, and catalyze the NADPH-dependent inactivation of aflatoxin dialdehyde.
AKR enzymes share a common (á/â)8 barrel folding pattern with a tetrad of conserved active site residues.
The structure determined of AKR7A3 is compatible with the known stereochemistry of aflatoxin dialdehyde conversion.