A comparison of rat and human liver formaldehyde dehydrogenase.

An NADand GSH-dependent formaldehyde dehydrogenase (formaldehyde: NAD* oxidoreductase, EC 1.2.I.Z) was purified from rat and human liver, and the properties of these enzymes were compared. The GSH requirement of the enzyme obtained from both species could not be replaced by dithiothreitol, CoA or cysteine, and NADP could not substitute for NAD. The pH optimum, and the Km of formaldehyde and NAD +, were similar for both rat and human liver formaldehyde dehydrogenase. By employing inhibitors such as folic acid and I,Io-phenanthroline, several qualitative differences between rat and human liver formaldehyde dehydrogenase have been detected. The molecular weight of purified human formaldehyde dehydrogenase was estimated at 9oooo. However, the molecular weight of human formaldehyde dehydrogenase appeared to be greater than 25o000 when it was determined in preparations which also contained alcohol dehydrogenase (alcohol:NAD~ oxidoreductase, EC I . I . I . I ) and aldehyde dehydrogenase (aldehyde:NAD + oxidoreductase, EC 1.2.1.3). These data suggest that formaldehyde dehydrogenase exists in a complex with other proteins or in a polymeric form until the ultimate steps in purification. The capacity for NAD-linked formaldehyde oxidation was greater in human liver than in rat liver. The possible implications of this are discussed in regard to the unique susceptibility of man to methanol poisoning.