Dihydrodiol dehydrogenase (DHDH)

Dihydrodiol dehydrogenase (DHDH) is a dimeric enzyme in the aldo-keto reductase superfamily that catalyzes the NADP+-dependent oxidation of trans-dihydrodiols derived from aromatic hydrocarbons to their corresponding catechols[1][2][4]. This enzyme plays a central role in the biotransformation of both xenobiotic and endogenous aromatic dihydrodiols, contributing to the detoxication or, in some cases, activation of polycyclic aromatic hydrocarbons (PAHs) into compounds that may be cytotoxic or genotoxic[3][4]. Structurally, DHDH features a classic dinucleotide binding domain and demonstrates high specificity for its substrate class[2][7]. Its physiological and pathological relevance arises from its dual capacity to facilitate detoxication as well as generate PAH metabolites implicated in oxidative stress and carcinogenesis[3]. Mutations in DHDH have been associated with developmental dysplasia of the hip, highlighting additional non-oncological importance[4].

Other names

Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase2DDHUM2DDD-xylose 1-dehydrogenaseD-xylose-NADP dehydrogenaseDimeric dihydrodiol dehydrogenase3-deoxyglucosone reductase

Drugs or small molecules targeting DHDH would likely act as enzyme inhibitors—blocking the NAD(P)+-dependent oxidation of dihydrodiols, modulating downstream catechol/quinone production, and potentially altering detoxication or bioactivation of xenobiotics[1][2][3].