Competition of pyruvate with physiological substrates for oxidation by the heart: implications for studies with hyperpolarized [1-13C]pyruvate.
Carbon 13 nuclear magnetic resonance (NMR) isotopomer analysis was used to measure the rates of oxidation of long-chain fatty acids, ketones, and pyruvate to determine the minimum pyruvate concentration ([pyruvate]) needed to suppress oxidation of these alternative substrates. Substrate mixtures were chosen to represent either the fed or fasted state. At physiological [pyruvate], fatty acids and ketones supplied the overwhelming majority of acetyl-CoA. Under conditions mimicking the fed state, 3 mM pyruvate provided approximately 80% of acetyl-CoA, but under fasting conditions 6 mM pyruvate contributed only 33% of acetyl-CoA. Higher [pyruvate], 10-25 mM, was associated with transient reduced cardiac output, but overall hemodynamic performance was unchanged after equilibration. These observations suggested that 3-6 mM pyruvate in the coronary arteries would be an appropriate target for studies with hyperpolarized [1-(13)C]pyruvate. However, the metabolic products of 3 mM hyperpolarized [1-(13)C]pyruvate could not be detected in the isolated heart during perfusion with a physiological mixture of substrates including 3% albumin. In the presence of albumin even at high concentrations of pyruvate, 20 mM, hyperpolarized H(13)CO(3)(-) could be detected only in the absence of competing substrates. Highly purified albumin (but not albumin from plasma) substantially reduced the longitudinal relaxation time of [1-(13)C]pyruvate. In conclusion, studies of cardiac metabolism using hyperpolarized [1-(13)C]pyruvate are sensitive to the effects of competing substrates on pyruvate oxidation.
Moreno
Karlos X
KX
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
Sabelhaus
Scott M
SM
Merritt
Matthew E
ME
Sherry
A Dean
AD
Malloy
Craig R
CR
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000418:Albumins / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D002302:Cardiac Output / Q000502:physiology; D003331:Coronary Vessels / Q000378:metabolism; D006334:Heart Function Tests; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D002250:Carbon Radioisotopes; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid