Linked Life Data

18042547

Source:http://linkedlifedata.com/resource/pubmed/id/18042547

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-1-14
pubmed:abstractText
Livers from mice lacking the carbohydrate-responsive element-binding protein (ChREBP) were compared with wild type (WT) mice to determine the effect of this transcription factor on hepatic energy metabolism. The pyruvate dehydrogenase complex was considerably more active in ChREBP(-/-) mice because of diminished pyruvate dehydrogenase kinase activity. Greater pyruvate dehydrogenase complex activity caused a stimulation of lactate and pyruvate oxidation, and it significantly impaired fatty acid oxidation in perfused livers from ChREBP(-/-) mice. This shift in mitochondrial substrate utilization led to a 3-fold reduction of the free cytosolic [NAD(+)]/[NADH] ratio, a 1.7-fold increase in the free mitochondrial [NAD(+)]/[NADH] ratio, and a 2-fold decrease in the free cytosolic [ATP]/[ADP][P(i)] ratio in the ChREBP(-/-) liver compared with control. Hepatic pyruvate carboxylase flux was impaired with ChREBP deletion secondary to decreased fatty acid oxidation, increased pyruvate oxidation, and limited pyruvate availability because of reduced activity of liver pyruvate kinase and malic enzyme, which replenish pyruvate via glycolysis and pyruvate cycling. Overall, the shift from fat utilization to pyruvate and lactate utilization resulted in a decrease in the energy of ATP hydrolysis and a hypo-energetic state in the livers of ChREBP(-/-) mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1670-8
pubmed:meshHeading
pubmed-meshheading:18042547-Animals, pubmed-meshheading:18042547-Blotting, Western, pubmed-meshheading:18042547-Cytosol, pubmed-meshheading:18042547-Energy Metabolism, pubmed-meshheading:18042547-Fatty Acids, pubmed-meshheading:18042547-Gene Deletion, pubmed-meshheading:18042547-Liver, pubmed-meshheading:18042547-Magnetic Resonance Spectroscopy, pubmed-meshheading:18042547-Mice, pubmed-meshheading:18042547-Mitochondria, pubmed-meshheading:18042547-Nuclear Proteins, pubmed-meshheading:18042547-Nucleotides, pubmed-meshheading:18042547-Oxidation-Reduction, pubmed-meshheading:18042547-Oxidative Phosphorylation, pubmed-meshheading:18042547-Oxygen Consumption, pubmed-meshheading:18042547-Perfusion, pubmed-meshheading:18042547-Protein-Serine-Threonine Kinases, pubmed-meshheading:18042547-Pyruvate Dehydrogenase Complex, pubmed-meshheading:18042547-Pyruvates, pubmed-meshheading:18042547-Substrate Specificity, pubmed-meshheading:18042547-Transcription Factors
pubmed:year
2008
pubmed:articleTitle
Carbohydrate-response element-binding protein deletion alters substrate utilization producing an energy-deficient liver.
pubmed:affiliation
Department of Biochemistry, Advanced Imaging Research Center, University of Texas Southwestern Medical School and Veterans Affairs, 5323 Harry Hines Blvd., Dallas, TX 75390-8854, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural