期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 41, 期 5, 页码 868-875出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2006.08.011
关键词
fatty acid oxidation; coenzyme A trapping; isotopomer analysis; compartmentation; acetyl-CoA synthetase; stable isotopes; acetate; acetyl-CoA; malonyl-CoA
资金
- NIDDK NIH HHS [5R01DK069752, R01 DK069752, U24 DK076174] Funding Source: Medline
We previously showed that, in the perfused rat heart, the capacity of n-fatty acids to generate mitochondrial acetyl-CoA decreases as their chain length increases. In the present study, we investigated whether the oxidation of a long-chain fatty acid, oleate, is inhibited by short-chain fatty acids, acetate or propionate (which do and do not generate mitochondrial acetyl-CoA, respectively). We perfused rat hearts with buffer containing 4 mM glucose, 0.2 mM pyruvate, I mM lactate, and various concentrations of either (i) [U-C-13]acetate, (ii) [U-C-13]acetate Plus [1-C-13] oleate, or (iii) unlabeled propionate plus [1-C-13]oleate. Using mass isotopomer analysis, we determined the contributions of the labeled substrates to the acetyl moiety of citrate (a probe of mitochondrial acetyl-CoA) and to malonyl-CoA. We found that acetate, even at low concentration, markedly inhibits the oxidation of [1-C-13]oleate in the heart, without change in malonyl-CoA concentration. We also found that propionate, at a concentration higher than I mM, decreases (i) the contribution of [1-C-13]oleate to mitochondrial acetyl-CoA and (ii) malonyl-CoA concentration. The inhibition by acetate or propionate of acetyl-CoA production from oleate probably results from a competition for mitochondrial CoA between the CoA-utilizing enzymes. (c) 2006 Elsevier Inc. All rights reserved.
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