Alcohol dehydrogenase RCH2OH + NAD -> RCHO + NADH + H+ Oxidoreductase (class 1) Function: defense against incoming alcohols and

xenobiotics, detoxification of endogenous acetaldehyde and lipid peroxidation products, role in retinol and hydroxysteroid oxidation, neuromediator metabolism Alcohol converted to acetaldehyde which turns into acetate Too much NADH inhibits gluconeogenesis and fatty acid oxidation Active site: 2 Zn2+ per subunit; one for catalytic and one for structure; active site Zn2+ is coordinated by 4 Cys residues; Zn2+ ligands include His and Cys residues; His and lle form Hbonds with alcohols; Phe, Val, Ala form H bonds with NADH; His-Thr general base catalysis to accept a proton from NADH (proton shuttle) Dimer interaction by His and Tyr- stacks against each other General reaction mechanism 1. NADH bind first 2. Structural change 3. Alcohol binds and coordinated in Zn2+ active site 4. His and Thr (proton shuttle) - H from NADH to aldehyde Inhibitors: heavy metals, etc