| Metabolism of alpha-ketoisocaproic acid in isolated perfused liver of cirrhotic rats. | |
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MedLine Citation:
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PMID: 7864106 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To determine the hepatic fate of alpha-ketoisocaproate (KIC) in cirrhosis, six groups of isolated rat livers were perfused with 0, 0.5, 1 (with or without alpha-[1-14C]KIC), 2, and 5 mM KIC; control livers from healthy rats were studied in parallel under similar conditions. KIC was rapidly removed by the normal livers, whereas uptake was lower in the cirrhotic livers at all concentrations tested (at 2 mM, 4.04 +/- 0.33 vs. 6.32 +/- 0.58 mumol/min; P < or = 0.05). The transamination pathway, evaluated by leucine exchanges, was more important in the cirrhotic livers (25.4 vs. 6.8% in controls at 2 mM). The incorporation of alpha-[1-14C]KIC in proteins of cirrhotic liver was increased compared with controls (0.25 +/- 0.04% of alpha-[1-14C]KIC was incorporated in proteins excreted in perfusate vs. 0.20 +/- 0.04 in controls; P < or = 0.05). In addition, a line of evidence suggests that glutamine rather than glutamate is the N donor for leucine synthesis from KIC. The decarboxylation pathway evaluated by beta-hydroxybutyrate production and by 14CO2 release from alpha-[1-14C]KIC was reduced, respectively, by 40-85% (according to KIC dose) and by 24% at 90 min in cirrhotic livers compared with healthy livers. These results indicate a dramatic modification of KIC metabolism in the cirrhotic liver; its uptake by the liver is decreased and its incorporation into proteins is increased via an enhancement of transamination to leucine, probably as a consequence of an inhibition of branched-chain keto acid dehydrogenase. |
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Authors:
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F Blonde-Cynober; F Plassart; J P de Bandt; C Rey; S K Lim; N Moukarbel; F Ballet; R Poupon; J Giboudeau; L Cynober |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: The American journal of physiology Volume: 268 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1995 Feb |
Date Detail:
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Created Date: 1995-03-21 Completed Date: 1995-03-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: E298-304 Citation Subset: IM |
Affiliation:
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Laboratoire de Biochimie A, Institut National de la Santé et de la Recherche Médicale U 402, Paris, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Keto Acids / metabolism* Liver / metabolism* Liver Cirrhosis, Experimental / metabolism* Male Perfusion Rats Rats, Sprague-Dawley Reference Values |
| Chemical | |
Reg. No./Substance:
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0/Keto Acids; 816-66-0/alpha-ketoisocaproic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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