THE VALINE CATABOLIC PATHWAY IN HUMAN LIVER - EFFECT OF CIRRHOSIS ON ENZYME-ACTIVITIES

The activities of key enzymes in the valine catabolic pathway-branched -chain aminotransferase, branched-chain alpha-keto acid dehydrogenase complex, methacrylyl (MC)-coenzyme A (CoA) hydratase (crotonase), and 3-hydroxyisobutyryl-CoA (HIB-CoA) hydrolase-were measured in normal an d cirrhotic human livers, Unlike rat Liver, which does not contain bra nched-chain aminotransferase, the aminotransferase activity in the nor mal liver was measurable and is increased somewhat in cirrhosis of the human liver, The total activity of branched-chain alpha-keto acid deh ydrogenase complex in the normal human liver was similar to 1% of that in rat Liver, and 20% to 30% of the complex was in the active form in both normal and cirrhotic livers. Only the actual activity of the enz yme was significantly decreased by cirrhosis, These results suggest th at human liver is less active than rat liver in the catabolism of bran ched-chain amino and alpha-keto acids. Activities of MC-CoA hydratase and HIB-CoA hydrolase in human liver were very high compared with that of branched-chain alpha-keto acid dehydrogenase complex, suggesting a n important role for these enzymes in catabolism of a potentially toxi c compound, MC-CoA, formed as an intermediate in the catabolism of val ine and isobutyrate, Cirrhosis resulted in a significant decrease in H IB-CoA hydrolase activity but had no effect on the citrate synthase ac tivity, suggesting that the decrease in HLB-CoA hydrolase activity doe s not reflect a general decrease in mitochondria but that it may contr ibute to cellular damage that culminates in liver failure.