Linked Life Data

7902355

Source:http://linkedlifedata.com/resource/pubmed/id/7902355

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
1994-1-4
pubmed:abstractText
The role of acetyl-coenzyme A carboxylase (ACC) in regulating fatty acid oxidation was investigated in isolated fatty acid perfused working rat hearts. Overall fatty acid oxidation rates were determined by addition of 1.2 mM [3H]palmitate to the perfusate of hearts in which the endogenous triglyceride pool was prelabeled with [14C]palmitate. Rates of both exogenous and endogenous fatty acid oxidation were measured by simultaneous measurement of 3H2O and 14CO2 production, respectively. A second series of hearts were perfused under similar conditions except that [U-14C]glucose was present in the perfusate for measurement of glucose oxidation rates. Addition of dichloroacetate (DCA, 1 mM) to the perfusate resulted in a dramatic stimulation of glucose oxidation (a 411% increase), with a parallel decrease in fatty acid oxidation (from 305 +/- 51 to 206 +/- 40 nmol/g dry weight.min.unit work). DCA treatment increased the contribution of glucose oxidation to ATP production from 7.1 to 30.6%, while decreasing the contribution of overall fatty acid oxidation from 92.9 to 69.4%. Tissue levels of malonyl-CoA in hearts treated with DCA were higher compared to controls (14.0 +/- 0.6 and 10.0 +/- 0.7 nmol/g dry weight, respectively) and were negatively correlated (r = -0.85) with overall fatty acid oxidation rates. Acetyl-CoA levels were also significantly higher in DCA-treated hearts, and a positive correlation (r = 0.88) was seen between myocardial acetyl-CoA and malonyl-CoA levels. This suggests that DCA treatment increased the supply of acetyl-CoA for ACC. Western blots revealed the presence of both the 280-kDa (ACC-280) and the 265-kDa (ACC-265) isoforms of ACC in cardiac tissue, with a predominance of ACC-280. The activity of ACC extracted from hearts was similar in both groups when assayed under optimal conditions of acetyl-CoA and citrate. However, using affinity purified ACC, it was demonstrated that heart ACC (predominantly ACC-280) had a higher Km for acetyl-CoA than ACC isolated from white adipose tissue (predominantly ACC-265). We conclude that ACC is an important regulator of fatty acid oxidation in the heart and that acetyl-CoA supply is a key determinant of heart ACC-280 activity. As acetyl-CoA levels increase, ACC-280 is activated resulting in an increase in malonyl-CoA inhibition of fatty acid oxidation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
268
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25836-45
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7902355-Acetyl-CoA Carboxylase, pubmed-meshheading:7902355-Acyl Coenzyme A, pubmed-meshheading:7902355-Animals, pubmed-meshheading:7902355-Carbon Radioisotopes, pubmed-meshheading:7902355-Carnitine O-Palmitoyltransferase, pubmed-meshheading:7902355-Chromatography, High Pressure Liquid, pubmed-meshheading:7902355-Citrates, pubmed-meshheading:7902355-Cytosol, pubmed-meshheading:7902355-Glucose, pubmed-meshheading:7902355-Glycolysis, pubmed-meshheading:7902355-Homeostasis, pubmed-meshheading:7902355-Kinetics, pubmed-meshheading:7902355-Male, pubmed-meshheading:7902355-Malonyl Coenzyme A, pubmed-meshheading:7902355-Mitochondria, Heart, pubmed-meshheading:7902355-Models, Biological, pubmed-meshheading:7902355-Myocardium, pubmed-meshheading:7902355-Oxidation-Reduction, pubmed-meshheading:7902355-Palmitic Acid, pubmed-meshheading:7902355-Palmitic Acids, pubmed-meshheading:7902355-Perfusion, pubmed-meshheading:7902355-Rats, pubmed-meshheading:7902355-Rats, Sprague-Dawley, pubmed-meshheading:7902355-Tritium
pubmed:year
1993
pubmed:articleTitle
Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart.
pubmed:affiliation
Department of Pediatrics, University of Alberta, Edmonton, Canada.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't