TY - JOUR
T1 - Competition of pyruvate with physiological substrates for oxidation by the heart
T2 - Implications for studies with hyperpolarized [1-13C]pyruvate
AU - Moreno, Karlos X.
AU - Sabelhaus, Scott M.
AU - Merritt, Matthew E.
AU - Sherry, A. Dean
AU - Malloy, Craig R.
PY - 2010/5
Y1 - 2010/5
N2 - 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 ∼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 [1-13C]pyruvate. "However, the metabolic products of 3 mM hyperpolarized [1-13C]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 H13CO3- 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 [1-13C]pyruvate. In conclusion, studies of cardiac metabolism using hyperpolarized [1-13C]pyruvate are sensitive to the effects of competing substrates on pyruvate oxidation.
AB - 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 ∼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 [1-13C]pyruvate. "However, the metabolic products of 3 mM hyperpolarized [1-13C]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 H13CO3- 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 [1-13C]pyruvate. In conclusion, studies of cardiac metabolism using hyperpolarized [1-13C]pyruvate are sensitive to the effects of competing substrates on pyruvate oxidation.
KW - Carbon-13
KW - Dynamic nuclear polarization
KW - Isolated rat heart
KW - Myocardium
KW - Nuclear magnetic resonance
KW - Pyruvate
KW - Substrate oxidation
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U2 - 10.1152/ajpheart.00656.2009
DO - 10.1152/ajpheart.00656.2009
M3 - Article
C2 - 20207817
AN - SCOPUS:77951836661
SN - 0363-6135
VL - 298
SP - H1556-H1564
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5
ER -