| Effects of clofibric acid on the activity and activity state of the hepatic branched-chain 2-oxo acid dehydrogenase complex. | |
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MedLine Citation:
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PMID: 1637295 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Feeding clofibric acid to rats caused little or no change in total activity of the liver branched-chain 2-oxo acid dehydrogenase complex (BCODC). No change in mass of liver BCODC was detected by immunoblot analysis in response to dietary clofibric acid. No changes in abundance of mRNAs for the BCODC E1 alpha, E1 beta and E2 subunits were detected by Northern-blot analysis. Likewise, dietary clofibric acid had no effect on the activity state of liver BCODC (percentage of enzyme in the dephosphorylated, active, form) of rats fed on a chow diet. However, dietary clofibric acid greatly increased the activity state of liver BCODC of rats fed on a diet deficient in protein. No stable change in liver BCODC kinase activity was found in response to clofibric acid in either chow-fed or low-protein-fed rats. Clofibric acid had a biphasic effect on flux through BCODC in hepatocytes prepared from low-protein-fed rats. Stimulation of BCODC flux at low concentrations was due to clofibric acid inhibition of BCODC kinase, which in turn allowed activation of BCODC by BCODC phosphatase. Inhibition of BCODC flux at high concentrations was due to direct inhibition of BCODC by clofibric acid. The results suggest that the effects of clofibric acid in vivo on branched-chain amino acid metabolism can be explained by the inhibitory effects of this drug on BCODC kinase. |
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Authors:
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Y Zhao; J Jaskiewicz; R A Harris |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Biochemical journal Volume: 285 ( Pt 1) ISSN: 0264-6021 ISO Abbreviation: Biochem. J. Publication Date: 1992 Jul |
Date Detail:
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Created Date: 1992-08-21 Completed Date: 1992-08-21 Revised Date: 2012-06-06 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 167-72 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis 46202-5122. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) Acyl-CoA Dehydrogenase Animals Blotting, Northern Blotting, Western Body Weight / drug effects Cells, Cultured Clofibric Acid / pharmacology* Dietary Proteins / administration & dosage Enzyme Activation Fatty Acid Desaturases / metabolism Ketone Oxidoreductases / antagonists & inhibitors, metabolism* Liver / drug effects, enzymology*, pathology Multienzyme Complexes / antagonists & inhibitors, metabolism* Organ Size / drug effects Protein Kinases / metabolism RNA, Messenger / metabolism Rats |
| Grant Support | |
ID/Acronym/Agency:
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DK19259/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dietary Proteins; 0/Multienzyme Complexes; 0/RNA, Messenger; 882-09-7/Clofibric Acid; EC 1.14.19.-/Fatty Acid Desaturases; EC 1.2.-/Ketone Oxidoreductases; EC 1.2.4.4/3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); EC 1.3.99.3/Acyl-CoA Dehydrogenase; EC 2.7.-/Protein Kinases; EC 2.7.11.4/(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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