Aldehyde dehydrogenase and acetaldehyde metabolism

Abstract

Ingested ethanol is first oxidized to acetaldehyde, primarily in the liver, then further oxidized to acetate. The oxidation of acetaldehyde is catalyzed by an NAD-dependent aldehyde dehydrogenase located in the liver mitochondrial matrix space. To date only one variant form of aldehyde dehydrogenase has been identified. Many Oriental people have an inactive mitochondrial form which possesses a lysine residue at position 487 rather than glutamate which is found in the active enzyme. We employed site directed mutagenesis to probe for active site residues in the enzyme and identified a number of residues which, if mutated, would produce an impaired or inactive enzyme. These mutations could be obtained by single base changes in the DNA coding for the enzyme. Though not identified in human populations, it is possible that these null mutants of the enzyme could exist in people deficient in active mitochondrial aldehyde dehydrogenase.