Zinc-dependent dehydrogenase (ZDD) (ZDD)

Zinc-dependent dehydrogenases represent a broad and essential superfamily of oxidoreductase enzymes, characterized by the presence of one or more zinc ions within their structure that serve either catalytic or structural roles (Source: UniProt). The most clinically significant members include alcohol dehydrogenases (ADH) and sorbitol dehydrogenase (SDH), which facilitate the reversible oxidation of alcohols to aldehydes or ketones using NAD+ or NADP+ as cofactors (Source: InterPro). ADH is primarily responsible for the metabolism of ethanol and is the target of pharmacological intervention in cases of toxic alcohol ingestion, such as methanol or ethylene glycol poisoning (Source: StatPearls). SDH is a key component of the polyol pathway, and its dysfunction or overactivity is implicated in the pathogenesis of diabetic complications like cataracts and neuropathy (Source: PubMed). Because these enzymes are involved in critical metabolic checkpoints, they are targeted by inhibitors like fomepizole to prevent the formation of toxic metabolites (Source: PubChem). The structural conservation of the zinc-binding site across this family presents both opportunities for broad-spectrum inhibition and challenges for achieving isoform-specific targeting in drug development.

Other names

Zinc-binding alcohol dehydrogenase superfamilyMedium-chain dehydrogenase/reductase familyMDR familyZinc-containing alcohol dehydrogenaseZinc-binding oxidoreductase

Competitive inhibition of the catalytic zinc active site, which prevents the enzyme from binding its alcohol or polyol substrates, thereby halting the oxidation process and the formation of toxic metabolites (Source: PubChem).