Subcellular localization of aldehyde dehydrogenase isozymes in human liver.

The subcellular distribution of aldehyde dehydrogenase (ALDH) isozymes in human liver was studied by isoelectric focusing and biochemical procedures in biopsied liver specimens obtained during surgical procedures. Four types of ALDH isozymes (ALDH I, II, III and IV) were identified in human liver by isoelectric focusing. In 6 of the 13 livers examined, ALDH I was not detected, indicating that about half of the Japanese people may be classified as the unusual type. ALDH I, which exhibits a low Km with respect to acetaldehyde (Ac-CHO), was located mainly in the mitochondrial and cytosolic fractions. ALDH II (high Km for Ac-CHO) was found to be localized mainly in the microsomal and cytosolic fractions. ALDH III and IV (very high Km for Ac-CHO) were localized in all fractions, except for ALDH III in the microsomal fraction. Biochemical analysis indicates that low Km ALDH activity was localized in the mitochondrial and cytosolic fractions, while high Km and whole ALDH activities were detected in all 3 fractions. More than 80% of the low Km, high Km and whole ALDH activity was found in the cytosolic fraction. These distribution patterns were quite different from those in rats. These results indicate that the results obtained in animal experiments cannot be directly applied to humans and that the main site of Ac-CHO oxidation in the human liver is in the cytosol.