The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases.

摘要: Aldehyde reductase [EC 1.1.1.2] and aldose 1.1.1.21] are monomeric NADPH-dependent oxidoreductases having wide substrate specificities for carbonyl compounds. These enzymes implicated in the development of diabetic complications by catalyzing reduction glucose to sorbitol. Enzyme inhibition as a direct pharmacokinetic approach prevention resulting from hyperglycemia diabetes has not been effective because nonspecificity inhibitors some appreciable side effects. To understand structural evolutionary relationship these enzymes, we cloned sequenced cDNAs coding aldehyde reductases human liver placental cDNA libraries. Human (open reading frame 316 amino acids) 65% identity (identical plus conservative substitutions) 325 acids). The two sequences have significant 2,5-diketogluconic acid corynebacterium, frog ρ-crystallin, bovine lung prostaglandin F synthase (reductase). Southern hybridization analysis genomic DNA indicates multigene system reductase, suggesting existence additional proteins. Thus, aldo-keto superfamily proteins may more hitherto fully appreciated role general cellular metabolism.