Alcohol dehydrogenase 7 (ADH7) (ADH7)

Alcohol dehydrogenase 7 (ADH7), also known as the sigma subunit of alcohol dehydrogenase or class IV ADH, is a cytosolic enzyme primarily localized in the epithelial tissues of the upper aerodigestive tract and the gastric mucosa. Unlike the more common hepatic class I ADHs, ADH7 is uniquely characterized by its high efficiency in oxidizing retinol to retinal, which serves as the rate-limiting step in the biosynthesis of retinoic acid, a critical signaling molecule for cellular growth and differentiation. Additionally, it contributes significantly to the first-pass metabolism of ethanol in the stomach, effectively reducing the amount of alcohol that enters systemic circulation. Genetic variations in the ADH7 gene have been strongly linked to alcohol dependence and an increased risk of cancers in the esophagus and upper aerodigestive tract, likely due to the localized production of toxic acetaldehyde. Pharmaceutically, ADH7 is inhibited by fomepizole, an antidote for toxic alcohol poisoning, and can be incidentally inhibited by common drugs like aspirin and H2-receptor antagonists, leading to increased bioavailability of dietary ethanol.

Other names

Alcohol dehydrogenase class 4 mu/sigma chainAlcohol dehydrogenase class IVSigma-ADHMu-ADHGastric alcohol dehydrogenaseAll-trans-retinol dehydrogenase [NAD(+)] ADH7Alcohol dehydrogenase 7 (class IV) mu or sigma polypeptide

Competitive inhibition of the enzyme's active site, typically by binding to the zinc-coordinated catalytic region, thereby blocking the oxidation of alcohol or retinol substrates.