Human liver class III alcohol and glutathione dependent formaldehyde dehydrogenase are the same enzyme

Abstract

Human liver class III alcohol dehydrogenase (χχ-ADH) and glutathione dependent formaldehyde dehydrogenase are the same enzyme. The enzyme, χχ-ADH, exhibits a k cat of 200 min −1 and a K m of 4 μM for the oxidation of formaldehyde, but only in the presence of GSH. In the absence of GSH the enzyme is essentially inactive toward formaldehyde but very active toward long chain alcohols. Thus, as in the rat (Koivusalo, M., Baumann, M., and Uotila, L. (1989) FEBS Letters 257, 105–109), the class III alcohol dehydrogenase and the GSH dependent formaldehyde dehydrogenase are identical enzymes. S-Hydroxymethyl derivatives of 8-thiooctanoate and lipoate are also very active substrates. The activity is specific for class III alcohol dehydrogenase; neither the class I and II nor the horse EE, ES, and SS isozymes oxidize hemithiolacetals. o-Phenanthroline competitively inhibits both activities and the two substrate types compete with each other.