K. Ishigure et al., Human liver disease decreases methacrylyl-CoA hydratase and beta-hydroxyisobutyryl-CoA hydrolase activities in valine catabolism, CLIN CHIM A, 312(1-2), 2001, pp. 115-121
Background: Methacrylyl-coenzyme A (MC-CoA) hydratase arid beta -hydroxyiso
butyryl-coenzyme A (HIB-CoA) hydrolase are key enzymes regulating the toxic
concentration of MC-CoA generated in valine catabolism. Materials and Meth
ods: We studied the activities and mRNA expression levels of these enzymes
in normal human livers and in human livers with chronic hepatitis, cirrhosi
s, or hepatocellular carcinoma. Results: The activities of both enzymes wer
e significantly lower by 36% to 46% in livers with cirrhosis or hepatocellu
lar carcinoma compared with normals, suggesting a decrease in the capabilit
y of detoxifying MC-CoA with these diseases. The mRNA levels for both enzym
es measured by quantitative polymerase chain reaction were significantly in
creased in livers with cirrhosis, but were not altered in those with chroni
c hepatitis or hepatocellular carcinoma when compared with normal livers. C
onclusion: Our results suggest that low levels of these enzyme activities i
n livers with cirrhosis or hepatocellular carcinoma are the result of postt
ranscriptional regulation in the damaged liver. (C) 2001 Elsevier Science B
.V. All rights reserved.