Alcohol dehydrogenase [iron-containing] 1 (ADHFE1)

Alcohol dehydrogenase [iron-containing] 1 (ADHFE1) is a mitochondrial enzyme that catalyzes the oxidation of gamma-hydroxybutyrate (GHB) to succinic semialdehyde, functioning independently of traditional cofactors such as NAD or NADP. It belongs to the iron-containing alcohol dehydrogenase family, found in mammals, bacteria, and fungi, and is involved in the metabolism of hydroxy- and oxo-acids. Mutations in ADHFE1 have been associated with rare inherited metabolic disorders involving abnormal accumulation of hydroxyglutaric acids. The enzyme plays a role in cellular metabolism and energy balance, but as of now, no drugs are known to selectively target it for therapeutic purposes. The full name in most authoritative databases and literature is "alcohol dehydrogenase [iron-containing] 1;" the gene symbol is ADHFE1. Functionally, it is distinct from classical zinc-containing alcohol dehydrogenases as it is iron-dependent and physiologically acts on substrates like GHB rather than ethanol. Clinical interest in ADHFE1 centers primarily around rare metabolic diseases rather than common drug targets; thus, it is technically a "target" as an enzyme but is not currently an established drug receptor or therapeutic target in standard pharmacology. Several aliases exist, most notably ADH8 and HOT, and in enzymatic databases, it is recognized as hydroxyacid-oxoacid transhydrogenase (EC 1.1.99.24). No known safety concerns or biomarkers are established for drug targeting, given the lack of therapeutics directed against ADHFE1.

Other names

ADHFE1ADH8HOThydroxyacid-oxoacid transhydrogenasealcohol dehydrogenase iron containing 1HMFT2263

Enzymatic oxidation of hydroxybutyrate to succinic semialdehyde (cofactor-independent), facilitating redox balance and intermediary metabolism