Human liver disease decreases methacrylyl-CoA hydratase and beta-hydroxyisobutyryl-CoA hydrolase activities in valine catabolism.

BACKGROUND

Methacrylyl-coenzyme A (MC-CoA) hydratase and beta-hydroxyisobutyryl-coenzyme A (HIB-CoA) hydrolase are key enzymes regulating the toxic concentration of MC-CoA generated in valine catabolism.

MATERIALS AND

METHODS

We studied the activities and mRNA expression levels of these enzymes in normal human livers and in human livers with chronic hepatitis, cirrhosis, or hepatocellular carcinoma.

RESULTS

The activities of both enzymes were significantly lower by 36% to 46% in livers with cirrhosis or hepatocellular carcinoma compared with normals, suggesting a decrease in the capability of detoxifying MC-CoA with these diseases. The mRNA levels for both enzymes measured by quantitative polymerase chain reaction were significantly increased in livers with cirrhosis, but were not altered in those with chronic hepatitis or hepatocellular carcinoma when compared with normal livers.

CONCLUSION

Our results suggest that low levels of these enzyme activities in livers with cirrhosis or hepatocellular carcinoma are the result of posttranscriptional regulation in the damaged liver.