title: Partitioning of pyruvate between oxidation and anaplerosis in swine hearts.
abstract: 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-(13)C(3)]lactate and/or [U-(13)C(3)] 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.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Panchal
authors.forename: B
authors.initials: B
authors.lastname: Comte
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.forename: T
authors.initials: T
authors.lastname: Kerwin
authors.forename: A
authors.initials: A
authors.lastname: Darvish
authors.forename: C
authors.initials: C
authors.lastname: des Rosiers
authors.forename: H
authors.initials: H
authors.lastname: Brunengraber
authors.forename: W C
authors.initials: WC
authors.lastname: Stanley
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000818:Animals; D002210:Caprylates / Q000494:pharmacology; D002247:Carbon Isotopes; D019343:Citric Acid / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000493:pharmacokinetics; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics; D007261:Infusions, Intra-Arterial; D019344:Lactic Acid / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors; D019289:Pyruvic Acid / Q000008:administration & dosage / Q000378:metabolism*; D013552:Swine; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D002210:Caprylates; D002247:Carbon Isotopes; D005230:Fatty Acids, Nonesterified; D011768:Pyruvate Dehydrogenase Complex; D019343:Citric Acid; D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose; D020155:3-Hydroxybutyric Acid