Respiratory control in heart muscle during fatty acid oxidation. Energy state or substrate-level regulation by Ca2+?
Fatty acids are the main fuel for the myocardium in vivo. They increase oxygen consumption, but the regulation of their beta-oxidation is not well known. Since Ca2+ and matrix volume have been implicated in the regulation of fatty acid oxidation in liver mitochondria, we set out to investigate the effects of Ca2+ on cellular respiration and energetics in the isolated perfused rat heart when oxidizing a short-chain fatty acid. Infusion of hexanoate increased oxygen consumption, while stepwise changes in the perfusate Ca2+ concentration in the range 0.5-2.5 mM caused the mechanical work output and oxygen consumption to change in parallel. Hexanoate addition increased the cellular energy state as determined by 31P NMR and evaluated from the cytosolic [ATP]/[ADP][Pi] ratio. During fatty acid infusion the energy state decreased slightly upon Ca(2+)-induced inotropy, and after discontinuation of the hexanoate infusion the de-energization was more pronounced. The fatty acid caused an extensive partially reversible reduction of flavoproteins and NAD with a slight tendency for oxidation during Ca(2+)-induced inotropy. The data are in agreement with the notion that oxygen consumption during fatty acid oxidation is mainly determined by the energy expenditure, even in the presence of Ca(2+)-induced alterations in the inotropic state. The constancy of the redox states of mitochondrial flavins and NADH/NAD during large changes in oxygen consumption is interpreted as indicating stabilization of the mitochondrial redox states by Ca(2+)-linked regulation.
Department of Medical Biochemistry, University of Oulu, Finland.
K H
KH
Vuorinen
A
A
Ala-Rämi
Y
Y
Yan
P
P
Ingman
I E
IE
Hassinen
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003326:Coronary Circulation; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005420:Flavoproteins / Q000378:metabolism; D006321:Heart / Q000502:physiology; D006706:Homeostasis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005230:Fatty Acids, Nonesterified; D005420:Flavoproteins; D009211:Myoglobin; D010710:Phosphates; D009243:NAD; D009249:NADP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D010100:Oxygen; D002118:Calcium