Aldo-keto reductase family 1 member A1 (AKR1A1)

Aldo-keto reductase family 1 member A1 (AKR1A1) is a cytosolic, NADPH-dependent enzyme in the aldo-keto reductase superfamily that catalyzes the reduction of a broad range of endogenous and exogenous aldehydes, including those generated by lipid peroxidation, glucose metabolism, and environmental toxins[1][2][3]. It plays a key role in cellular detoxification, redox balance, and, in other mammals, ascorbic acid (vitamin C) biosynthesis (although this pathway is inactive in humans)[1][2]. AKR1A1 also participates in drug metabolism, particularly influencing the activation or inactivation of chemotherapeutic agents such as anthracyclines, impacting both efficacy and resistance[3]. AKR1A1 is broadly expressed, especially in kidney and liver, and protects cells against oxidative damage by metabolizing reactive aldehydes[1][2][3]. Genetic knockout models highlight its importance in bone health and metabolism; loss of AKR1A1 impairs ascorbic acid production and increases oxidative injury phenotypes, making it a potential biomarker and modifier of disease risk[2].

Other names

ALDR1ALRScorRDD3Alcohol dehydrogenase [NADP(+)]Aldehyde reductaseGlucuronate reductaseGlucuronolactone reductaseS-nitroso-CoA reductasedihydrodiol dehydrogenase 3ARMHEL-S-6HEL-S-165mPepididymis secretory protein Li 6epididymis secretory sperm binding protein Li 165mP

Reduction/inactivation of toxic aldehydes (including drug metabolites and by-products); Reduction of chemotherapeutic anthracyclines, leading to changes in drug toxicity and efficacy