Aflatoxin B1 aldehyde reductase member 2 is an enzyme that in humans is encoded by the AKR7A2 gene. It catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate and may have an important role in producing the neuromodulator gamma-hydroxybutyrate (GHB). AKR7A2 has broad substrate specificity and NADPH-dependent aldehyde reductase activity towards 2-carboxybenzaldehyde, 2-nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). AKR7A2 can reduce 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro) and reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. It may be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen.
Background References
1. "Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases that associate with the Golgi apparatus define a distinct subclass of aldo-keto reductase 7 family proteins." Kelly V.P., Sherratt P.J., Crouch D.H., Hayes J.D. Biochem. J. 366:847-861(2002)
2. "Synthesis and catabolism of gamma-hydroxybutyrate in SH-SY5Y human neuroblastoma cells: role of the aldo-keto reductase AKR7A2." Lyon R.C., Johnston S.M., Watson D.G., McGarvie G., Ellis E.M. J. Biol. Chem. 282:25986-25992(2007) "Genetic variation of aflatoxin B1 aldehyde reductase genes (AFAR) in human tumour cells." Praml C., Schulz W., Claas A., Mollenhauer J., Poustka A., Ackermann R., Schwab M., Henrich K.-O.Cancer Lett. 272:160-166(2008)
Sequence Similarity
Belongs to the aldo/keto reductase family. Aldo/keto reductase 2 subfamily.
Tissue Specificity
Detected in brain, liver, small intestine and testis, and at lower levels in heart, prostate, skeletal muscle and spleen. Detected in kidney proximal and distal tubules, endothelial cells lining the Bowman's capsules and some cysts. Detected at low levels in lung and pancreas (at protein level). Widely expressed.