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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1989-6-9
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pubmed:abstractText |
The effect of valproate (0.01-10 mM), an antiepileptic drug inducing hyperammonemia in humans, was studied in vitro on a suspension of renal cortical tubules (greater than 85% proximal tubules) obtained from six normal dogs. When these tubules were incubated with 1 mM glutamine, the addition of valproate accelerated glutamine uptake, ammoniagenesis, and the production of alanine, lactate, and pyruvate. With 5 mM glutamine, a rise in glutamate accumulation, a much greater synthesis of alanine, an important aspartate production, and a striking accumulation of lactate and pyruvate were observed. With 1 or 5 mM lactate, lactate utilization and gluconeogenesis were markedly reduced with increasing concentrations of valproate. Oxygen consumption was reduced by only 15-20% by 10 mM valproate. The accelerated glutamine utilization resulting from valproate could not be prevented by aminooxyacetate, an inhibitor of transamination. Valproate also reduced various enzymatic activities, a finding that could not explain its metabolic effects. Four sites of action may explain these various metabolic changes: (i) a stimulation of mitochondrial glutamine transport, (ii) an increase in the flux of glutamate to malate, and (iii) a reduction in the net oxidation of pyruvate and (iv) in the flux through pyruvate carboxylase.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aminooxyacetic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamates,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamine,
http://linkedlifedata.com/resource/pubmed/chemical/Lactates,
http://linkedlifedata.com/resource/pubmed/chemical/Pyruvates,
http://linkedlifedata.com/resource/pubmed/chemical/Valproic Acid
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0008-4212
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
88-97
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:2496913-Aminooxyacetic Acid,
pubmed-meshheading:2496913-Animals,
pubmed-meshheading:2496913-Dogs,
pubmed-meshheading:2496913-Glutamates,
pubmed-meshheading:2496913-Glutamine,
pubmed-meshheading:2496913-Kidney Cortex,
pubmed-meshheading:2496913-Kidney Tubules,
pubmed-meshheading:2496913-Lactates,
pubmed-meshheading:2496913-Oxygen Consumption,
pubmed-meshheading:2496913-Pyruvates,
pubmed-meshheading:2496913-Valproic Acid
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pubmed:year |
1989
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pubmed:articleTitle |
Metabolic effects of valproate on dog renal cortical tubules.
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pubmed:affiliation |
Renal Service, Notre-Dame Hospital, Montréal, Qué., Canada.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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