Aldo-keto reductase family 1 member B15 (AKR1B15)

Aldo-keto reductase family 1 member B15 (AKR1B15) is a mitochondrial enzyme belonging to the aldo-keto reductase superfamily, highly homologous to AKR1B10 but possessing distinct substrate specificity and kinetic properties[1][2][3]. AKR1B15 exhibits potent catalytic activity towards a wide range of carbonyl-containing molecules, including retinoids, medium-chain aldehydes and ketones, and select sex steroids, functioning predominantly as a reductive enzyme with 17β-hydroxysteroid dehydrogenase activity and utilizing NADP(H) as a cofactor[1][3]. It is expressed principally in steroid-sensitive tissues (such as placenta, testis, and adipose tissue), and alternative splicing generates two isoforms with differing subcellular localization and activity: AKR1B15.1 (mitochondrial, catalytically active) and AKR1B15.2 (cytosolic, with no detected activity)[3]. Despite similarity to other AKR1B enzymes, AKR1B15 is distinguished by its higher catalytic efficiency with ketone, dicarbonyl, and 9-cis-retinaldehyde substrates, narrower inhibitor selectivity, and smaller, more hydrophobic active site[1][2]. Inhibitor studies identify JF0064 and lithocholic acid as significant inhibitors, but most classical AKR inhibitors are ineffective against AKR1B15[2]. Its full physiological role, particularly in endocrine regulation and retinoid metabolism, remains under investigation[1][2][3].

Other names

Estradiol 17-beta-dehydrogenase AKR1B15Farnesol dehydrogenaseTestosterone 17beta-dehydrogenaseAKR1B10LAKR1B15.1Putative aldo-keto reductase family 1 member B15Aldo-keto reductase family 1 member B15, mitochondrial

Competitive inhibition of enzymatic activity (e.g., JF0064 inhibits AKR1B15 reductase function) Non-competitive inhibition by select steroids