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.
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.
Authors: Sadakatali S Gori; Pawel Lorkiewicz; Daniel S Ehringer; Alex C Belshoff; Richard M Higashi; Teresa W-M Fan; Michael H Nantz Journal: Anal Bioanal Chem Date: 2014-05-25 Impact factor: 4.142
Authors: Natalie M Zahr; Richard L Bell; Heather N Ringham; Edith V Sullivan; Frank A Witzmann; Adolf Pfefferbaum Journal: Pharmacol Biochem Behav Date: 2011-03-23 Impact factor: 3.533