Isozyme patterns of branched-chain amino acid transaminase in human tissues and tumors.

The isozymes (enzymes I and III) of branched-chain amino acid transaminase (EC 2.6.1.42) from various human tissues were separated by DEAE-cellulose column chromatography. Their distributions were found to be considerably different from those in rat tissues reported before. In rats, all tissues examined contained enzyme I and in addition enzyme II was found in the liver and enzyme III in the brain, ovary, and placenta. In humans, however, enzyme II was not found in any tissues examined including the liver, and enzyme III was found in many other tissues besides brain, ovary, and placenta. All normal human tissues except the lung, ovary, and brain contain less enzyme III than enzyme I. Various human cancers of the liver, kidney, stomach, pancreas, and uterus showed significantly higher ratios of enzyme III to enzyme I than those of the corresponding normal tissues. Fetal liver and kidney also contained much higher concentrations of enzyme III than adult liver and kidney. These findings suggest that change of the isozyme pattern of this enzyme in cancer is similar in humans and rats, and that cancer tissues tend to express more immature phenotypes than normal tissues. Enzymes I and III of human tissues showed the same substrate specificities for valine, leucine, and isoleucine, and these amino acids competed for the active site of the enzyme. Thus the hereditary diseases, hypervalinemia and hyperisoleucine-leucinemia, may be due to genetic alteration of the enzyme protein, resulting in change of its substrate specificity.