Competition between acetate and oleate for the formation of malonyl-CoA and mitochondrial acetyl-CoA in the perfused rat heart.
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, 1 mM lactate, and various concentrations of either (i) [U-(13)C]acetate, (ii) [U-(13)C]acetate plus [1-(13)C]oleate, or (iii) unlabeled propionate plus [1-(13)C]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-(13)C]oleate in the heart, without change in malonyl-CoA concentration. We also found that propionate, at a concentration higher than 1 mM, decreases (i) the contribution of [1-(13)C]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.
Bian
Fang
F
Department of Nutrition, Case Western Reserve University, 2109 Adelbert Road, Room BRB923, Cleveland, OH 44106-4906, USA.
Kasumov
Takhar
T
Jobbins
Kathryn A
KA
Minkler
Paul E
PE
Anderson
Vernon E
VE
Kerner
Janos
J
Hoppel
Charles L
CL
Brunengraber
Henri
H
D000085:Acetates / Q000737:chemistry; D000105:Acetyl Coenzyme A / Q000096:biosynthesis*; D000818:Animals; D005227:Fatty Acids; D066298:In Vitro Techniques; D008297:Male; D008316:Malonyl Coenzyme A / Q000096:biosynthesis*; D008929:Mitochondria, Heart / Q000378:metabolism*; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism*; D010084:Oxidation-Reduction; D010477:Perfusion; D011422:Propionates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D000085:Acetates; D005227:Fatty Acids; D011422:Propionates; D019301:Oleic Acid; D008316:Malonyl Coenzyme A; D000105:Acetyl Coenzyme A; C029658:propionic acid