pubmed-article:7902355 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:7902355 | lifeskim:mentions | umls-concept:C0018787 | lld:lifeskim |
pubmed-article:7902355 | lifeskim:mentions | umls-concept:C0001022 | lld:lifeskim |
pubmed-article:7902355 | lifeskim:mentions | umls-concept:C1158369 | lld:lifeskim |
pubmed-article:7902355 | pubmed:issue | 34 | lld:pubmed |
pubmed-article:7902355 | pubmed:dateCreated | 1994-1-4 | lld:pubmed |
pubmed-article:7902355 | 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. | lld:pubmed |
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pubmed-article:7902355 | pubmed:language | eng | lld:pubmed |
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pubmed-article:7902355 | pubmed:citationSubset | IM | lld:pubmed |
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pubmed-article:7902355 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:7902355 | pubmed:month | Dec | lld:pubmed |
pubmed-article:7902355 | pubmed:issn | 0021-9258 | lld:pubmed |
pubmed-article:7902355 | pubmed:author | pubmed-author:WittersL ALA | lld:pubmed |
pubmed-article:7902355 | pubmed:author | pubmed-author:GambleJJ | lld:pubmed |
pubmed-article:7902355 | pubmed:author | pubmed-author:LopaschukG... | lld:pubmed |
pubmed-article:7902355 | pubmed:author | pubmed-author:SaddikMM | lld:pubmed |
pubmed-article:7902355 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:7902355 | pubmed:day | 5 | lld:pubmed |
pubmed-article:7902355 | pubmed:volume | 268 | lld:pubmed |
pubmed-article:7902355 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:7902355 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:7902355 | pubmed:pagination | 25836-45 | lld:pubmed |
pubmed-article:7902355 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
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pubmed-article:7902355 | pubmed:year | 1993 | lld:pubmed |
pubmed-article:7902355 | pubmed:articleTitle | Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart. | lld:pubmed |
pubmed-article:7902355 | pubmed:affiliation | Department of Pediatrics, University of Alberta, Edmonton, Canada. | lld:pubmed |
pubmed-article:7902355 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:7902355 | pubmed:publicationType | In Vitro | lld:pubmed |
pubmed-article:7902355 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
pubmed-article:7902355 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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