title: Transpulmonary pyruvate kinetics.
abstract: Shuttling of intermediary metabolites, such as pyruvate, contributes to the dynamic energy and biosynthetic needs of tissues. Tracer kinetic studies offer a powerful tool to measure the metabolism of substrates like pyruvate that are simultaneously taken up from and released into the circulation by organs. However, we understood that during each circulatory passage, the entire cardiac output transits the pulmonary circulation. Therefore, we examined the transpulmonary pyruvate kinetics in an anesthetized rat model during an unstimulated (Con), lactate clamp (LC), and epinephrine infusion (Epi) conditions using a primed-continuous infusion of [U-¹³C]pyruvate. Compared with Con and Epi stimulation, LC significantly increased mixed central venous ([v]) and arterial ([a]) pyruvate concentrations (P < 0.05). We hypothesized that the lungs, specifically the pulmonary capillary beds are sites of simultaneous production and removal of pyruvate and contributes significantly to whole body carbohydrate intermediary metabolism. Transpulmonary net pyruvate balances were positive during all three conditions, indicating net pyruvate uptake. Net balance was significantly greater during epinephrine stimulation compared with the unstimulated control (P < 0.05). Tracer-measured pyruvate fractional extraction averaged 42.8 ± 5.8% for all three conditions and was significantly higher during epinephrine stimulation (P < 0.05) than during either Con or LC conditions, that did not differ from each other. Pyruvate total release (tracer measured uptake - net balance) was significantly higher during epinephrine stimulation (400 ± 100 μg/min) vs. Con (30 ± 20 μg/min) (P < 0.05). These data are interpreted to mean that significant pyruvate extraction occurs during circulatory transport across lung parenchyma. The extent of pulmonary parenchymal pyruvate extraction predicts high expression of monocarboxylate (lactate/pyruvate) transporters (MCTs) in the tissue. Western blot analysis of whole lung homogenates detected three isoforms, MCT1, MCT2, and MCT4. We conclude that a major site of circulating pyruvate extraction resides with the lungs and that during times of elevated circulating lactate, pyruvate, or epinephrine stimulation, pyruvate extraction is increased.
authors.affiliation: Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley California, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Johnson
authors.forename: Rajaa
authors.initials: R
authors.lastname: Hussien
authors.forename: Michael A
authors.initials: MA
authors.lastname: Horning
authors.forename: George A
authors.initials: GA
authors.lastname: Brooks
mesh_terms: D000322:Adrenergic Agonists / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002196:Capillaries / Q000378:metabolism; D002247:Carbon Isotopes; D002302:Cardiac Output; D004734:Energy Metabolism / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage; D005260:Female; D007201:Indicator Dilution Techniques; D007262:Infusions, Intravenous; D007700:Kinetics; D019344:Lactic Acid / Q000008:administration & dosage; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D011652:Pulmonary Circulation; D019289:Pyruvic Acid / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D000322:Adrenergic Agonists; D002247:Carbon Isotopes; D004837:Epinephrine; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D019289:Pyruvic Acid; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C516342:Slc16a3 protein, rat; C091633:Slc16a7 protein, rat