Polyol dehydrogenase that catalyzes the reversible NAD(+)-dependent oxidation of various sugar alcohols. Is mostly active with D-sorbitol (D-glucitol), L-threitol, xylitol and ribitol as substrates, leading to the C2-oxidized products D-fructose, L-erythrulose, D-xylulose, and D-ribulose, respectively (PubMed:3365415). Is a key enzyme in the polyol pathway that interconverts glucose and fructose via sorbitol, which constitutes an important alternate route for glucose metabolism. The polyol pathway is believed to be involved in the etiology of diabetic complications, such as diabetic neuropathy and retinopathy, induced by hyperglycemia (PubMed:12962626, PubMed:29966615, PubMed:25105142). May play a role in sperm motility by using sorbitol as an alternative energy source for sperm motility (PubMed:16278369). May have a more general function in the metabolism of secondary alcohols since it also catalyzes the stereospecific oxidation of (2R,3R)-2,3-butanediol. To a lesser extent, can also oxidize L-arabinitol, galactitol and D-mannitol and glycerol in vitro. Oxidizes neither ethanol nor other primary alcohols. Cannot use NADP(+) as the electron acceptor (PubMed:3365415). H(+) + keto-D-fructose + NADH = D-sorbitol + NAD(+) L-threitol + NAD(+) = H(+) + L-erythrulose + NADH NAD(+) + xylitol = D-xylulose + H(+) + NADH NAD(+) + ribitol = D-ribulose + H(+) + NADH (R,R)-butane-2,3-diol + NAD(+) = (R)-acetoin + H(+) + NADH L-iditol + NAD(+) = H(+) + keto-L-sorbose + NADH Binds 1 zinc ion per subunit. Inhibited by CP-166,572, an inhibitor that is competitive with fructose (PubMed:12962626). Also competitively inhibited by phenanthroline and 4-methylpyrazole in vitro (PubMed:3365415). kcat is 1.7 sec(-1) for the oxidation of D-sorbitol at pH 7.1, and 5.2 sec(-1) at pH 10.0. kcat is 5.9 sec(-1) the oxidation of xylitol as substrate at pH 10.0. kcat is 5.3 sec(-1) the oxidation of L-threitol as substrate at pH 10.0. kcat is 4.2 sec(-1) the oxidation of (2R,3R)-2,3-butanediol as substrate at pH 10.0. kcat is 45 sec(-1) for the reduction of D-fructose at pH 7.1. Homotetramer. Associated with mitochondria of the midpiece and near the plasma membrane in the principal piece of the flagellum. Also found in the epididymosome, secreted by the epididymal epithelium and that transfers proteins from the epididymal fluid to the sperm surface. Expressed in liver (PubMed:3365415). Expressed in kidney and epithelial cells of both benign and malignant prostate tissue. Expressed in epididymis (at protein level). Up-regulated by androgens and down-regulated by castration. The disease is caused by variants affecting the gene represented in this entry. Belongs to the zinc-containing alcohol dehydrogenase family.