| Monochloroacetic acid inhibits liver gluconeogenesis by inactivating glyceraldehyde-3-phosphate dehydrogenase. | |
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MedLine Citation:
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PMID: 15720133 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We previously reported that a lethal dose of monochloroacetate (MCA) causes severe hypoglycemia and lactic acidosis. MCA has been thought to inhibit mitochondrial aconitase; however, the exact effect of MCA on hepatic glucose metabolism is not clear. In this study, we investigated the effects of MCA on liver gluconeogenesis using an isolated perfused rat liver system. Gluconeogenesis from 2.5 mM lactate was inhibited by 1 mM MCA and was completely abolished after 2 h of perfusion. Levels of citric acid cycle intermediates such as citrate, isocitrate, and 2-oxoglutarate (2-OG) were significantly reduced by MCA. The finding that the levels of citrate and 2-OG were similarly reduced (to 31 and 36% of control, respectively) indicates that aconitase was not inhibited by MCA. On the contrary, gluconeogenesis from glycerol, which can be converted to glucose without glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was not inhibited by MCA. GAPDH was inactivated by MCA in vitro, but enolase, phosphoglycerate mutase, and phosphoglycerate kinase were not inactivated at the same or higher concentrations of MCA. Furthermore, GAPDH activity in the MCA-perfused liver decreased to 33-42% of control and that in the liver of rats exposed to MCA was reduced to 19% of control. We concluded that MCA inactivates GAPDH, and this is the cause of the inhibition of liver gluconeogenesis. |
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Authors:
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Akiko Sakai; Hiroyasu Shimizu; Koichi Kono; Eisuke Furuya |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chemical research in toxicology Volume: 18 ISSN: 0893-228X ISO Abbreviation: Chem. Res. Toxicol. Publication Date: 2005 Feb |
Date Detail:
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Created Date: 2005-02-21 Completed Date: 2005-09-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8807448 Medline TA: Chem Res Toxicol Country: United States |
Other Details:
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Languages: eng Pagination: 277-82 Citation Subset: IM |
Affiliation:
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Department of Chemistry, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan. asakai@art.osaka-med.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetic Acids
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pharmacology* Animals Enzyme Inhibitors / pharmacology* Gluconeogenesis / drug effects* Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors* Glycerol / pharmacology Lactic Acid / pharmacology Liver / drug effects, metabolism* Male Rats Rats, Sprague-Dawley Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Acetic Acids; 0/Enzyme Inhibitors; 50-21-5/Lactic Acid; 56-81-5/Glycerol; 79-11-8/chloroacetic acid; EC 1.2.1.-/Glyceraldehyde-3-Phosphate Dehydrogenases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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