Partitioning of pyruvate between oxidation and anaplerosis in swine hearts

AR Panchal, B Comte, H Huang… - American Journal …, 2000 - journals.physiology.org
AR Panchal, B Comte, H Huang, T Kerwin, A Darvish, CD Rosiers, H Brunengraber
American Journal of Physiology-Heart and Circulatory Physiology, 2000journals.physiology.org
The goal of this study was to measure flux through pyruvate carboxylation and
decarboxylation in the heart in vivo. These rates were measured in the anterior wall of
normal anesthetized swine hearts by infusing [U-13C3] lactate and/or [U-13C3] pyruvate into
the left anterior descending (LAD) coronary artery. After 1 h, the tissue was freeze-clamped
and analyzed by gas chromatography-mass spectrometry for the mass isotopomer
distribution of citrate and its oxaloacetate moiety. LAD blood pyruvate and lactate …
The goal of this study was to measure flux through pyruvate carboxylation and decarboxylation in the heart in vivo. These rates were measured in the anterior wall of normal anesthetized swine hearts by infusing [U-13C3]lactate and/or [U-13C3] pyruvate into the left anterior descending (LAD) coronary artery. After 1 h, the tissue was freeze-clamped and analyzed by gas chromatography-mass spectrometry for the mass isotopomer distribution of citrate and its oxaloacetate moiety. LAD blood pyruvate and lactate enrichments and concentrations were constant after 15 min of infusion. Under near-normal physiological concentrations of lactate and pyruvate, pyruvate carboxylation and decarboxylation accounted for 4.7 ± 0.3 and 41.5 ± 2.0% of citrate formation, respectively. Similar relative fluxes were found when arterial pyruvate was raised from 0.2 to 1.1 mM. Addition of 1 mM octanoate to 1 mM pyruvate inhibited pyruvate decarboxylation by 93% without affecting carboxylation. The absence of M1 and M2 pyruvate demonstrated net irreversible pyruvate carboxylation. Under our experimental conditions we found that pyruvate carboxylation in the in vivo heart accounts for at least 3–6% of the citric acid cycle flux despite considerable variation in the flux through pyruvate decarboxylation.
American Physiological Society