Abstract
Metabolic effects of increased mechanical work were studied by comparing isolated pumping rat hearts perfused by the atrial-filling technique with aortic-perfused non-pumping hearts perfused by the technique of Langendorff. The initial medium usually contained glucose (11 mm) and palmitate (0.6 mm bound to 0.1 mm albumin). During increased heart work (comparing pumping with non-pumping hearts) the uptake of oxygen and glucose increased threefold, but that of free fatty acids was unchanged. Tissue contents of alpha-oxoglutarate, NH4+, malate, lactate, pyruvate and Pi rose with increased heart work, but contents of ATP, phosphocreatine and citrate fell. Ketone bodies were produced with a ratio of beta-hydroxybutyrate/acetoacetate of about 3:1 in both pumping and non-pumping hearts but with higher net production rates in non-pumping hearts. When ketone bodies were added in relatively high concentrations (total 4 mm) to a glucose (11 mm) medium the medium, ratios of beta-hydroxybutyrate/acetoacetate were not steady even after 60 min of perfusion. The validity of calculating mitochondrial free NAD+/NADH ratios from the tissue contents of the reactants of the glutamate dehydrogenase system or the beta-hydroxybutyrate dehydrogenase system is assessed. The activities of these enzymes are considerably less in the rat heart than in the rat liver, introducing reservations into the application to the heart of the principles used by Williamson et al. (1967) for calculation of mitochondrial free NAD+/NADH ratios of liver mitochondria...
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- Adler-Kastner L., Keller B., Kraupp O., Stühlinger W., Turnheim K. The myocardial oxaloacetate level in normal and chronic alloxan-diabetic rats in vivo. J Mol Cell Cardiol. 1972 Aug;4(4):391–400. doi: 10.1016/0022-2828(72)90085-5. [DOI] [PubMed] [Google Scholar]
- Berenblum I., Chain E. An improved method for the colorimetric determination of phosphate. Biochem J. 1938 Feb;32(2):295–298. doi: 10.1042/bj0320295. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brosnan J. T., Williamson D. H. Mechanisms for the formation of alanine and aspartate on rat liver in vivo after administration of ammonium chloride. Biochem J. 1974 Mar;138(3):453–462. doi: 10.1042/bj1380453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chain E. B., Mansford K. R., Opie L. H. Effects of insulin on the pattern of glucose metabolism in the perfused working and Langendorff heart of normal and insulin-deficient rats. Biochem J. 1969 Nov;115(3):537–546. doi: 10.1042/bj1150537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chance B., Salkovitz I. A., Kovach A. G. Kinetics of mitochondrial flavoprotein and pyridine nucleotide in perfused heart. Am J Physiol. 1972 Jul;223(1):207–218. doi: 10.1152/ajplegacy.1972.223.1.207. [DOI] [PubMed] [Google Scholar]
- Cryer A., Bartley W. The enzymic make-up of the left and right ventricles of the normal rat heart and the changes shown on exposure to exercise and hypoxic exercise. J Mol Cell Cardiol. 1974 Feb;6(1):61–71. doi: 10.1016/0022-2828(74)90007-8. [DOI] [PubMed] [Google Scholar]
- EVANS J. R., OPIE L. H., SHIPP J. C. METABOLISM OF PALMITIC ACID IN PERFUSED RAT HEART. Am J Physiol. 1963 Oct;205:766–770. doi: 10.1152/ajplegacy.1963.205.4.766. [DOI] [PubMed] [Google Scholar]
- Fath P. A., Kako K. J. Glycolytic and tricarboxylic acid cycle intermediates during cardiac arrest and recovery in eu-, hyper- and hypothyroid rats. J Mol Cell Cardiol. 1973 Aug;5(4):359–373. doi: 10.1016/0022-2828(73)90028-x. [DOI] [PubMed] [Google Scholar]
- Garland P. B. Control of citrate synthesis in mitochondria. Biochem Soc Symp. 1968;27:41–60. [PubMed] [Google Scholar]
- Garland P. B., Newsholme E. A., Randle P. J. Regulation of glucose uptake by muscle. 9. Effects of fatty acids and ketone bodies, and of alloxan-diabetes and starvation, on pyruvate metabolism and on lactate-pyruvate and L-glycerol 3-phosphate-dihydroxyacetone phosphate concentration ratios in rat heart and rat diaphragm muscles. Biochem J. 1964 Dec;93(3):665–678. doi: 10.1042/bj0930665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HOHORST H. J., KREUTZ F. H., BUECHER T. [On the metabolite content and the metabolite concentration in the liver of the rat]. Biochem Z. 1959;332:18–46. [PubMed] [Google Scholar]
- KIRSTEN E., GEREZ C., KIRSTEN R. [An enzymatic microdetermination method for ammonia, specifically for extracts of animal tissues and fluids. Determination of NH4 ions in blood]. Biochem Z. 1963;337:312–319. [PubMed] [Google Scholar]
- Kannengiesser G. J., Lubbe W. F., Opie L. H. Experimental myocardial infarction with left ventricular failure in the isolated perfused rat heart. Effects of isoproterenol and pacing. J Mol Cell Cardiol. 1975 Feb;7(2):135–151. doi: 10.1016/0022-2828(75)90015-2. [DOI] [PubMed] [Google Scholar]
- Kosicki G. W., Lee L. P. Effect of divalent metal ions on nucleotide inhibition of pig heart citrate synthase. J Biol Chem. 1966 Aug 10;241(15):3571–3574. [PubMed] [Google Scholar]
- Krebs H. A. Rate control of the tricarboxylic acid cycle. Adv Enzyme Regul. 1970;8:335–353. doi: 10.1016/0065-2571(70)90028-2. [DOI] [PubMed] [Google Scholar]
- LEHNINGER A. L., SUDDUTH H. C., WISE J. B. D-beta-Hydroxybutyric dehydrogenase of muitochondria. J Biol Chem. 1960 Aug;235:2450–2455. [PubMed] [Google Scholar]
- LaNoue K. F., Bryla J., Williamson J. R. Feedback interactions in the control of citric acid cycle activity in rat heart mitochondria. J Biol Chem. 1972 Feb 10;247(3):667–679. [PubMed] [Google Scholar]
- LaNoue K. F., Walajtys E. I., Williamson J. R. Regulation of glutamate metabolism and interactions with the citric acid cycle in rat heart mitochondria. J Biol Chem. 1973 Oct 25;248(20):7171–7183. [PubMed] [Google Scholar]
- LaNoue K. F., Williamson J. R. Interrelationships between malate-aspartate shuttle and citric acid cycle in rat heart mitochondria. Metabolism. 1971 Feb;20(2):119–140. doi: 10.1016/0026-0495(71)90087-4. [DOI] [PubMed] [Google Scholar]
- MORGAN H. E., HENDERSON M. J., REGEN D. M., PARK C. R. Regulation of glucose uptake in muscle. I. The effects of insulin and anoxia on glucose transport and phosphorylation in the isolated, perfused heart of normal rats. J Biol Chem. 1961 Feb;236:253–261. [PubMed] [Google Scholar]
- Moellering H., Gruber W. Determination of citrate with citrate lyase. Anal Biochem. 1966 Dec;17(3):369–376. doi: 10.1016/0003-2697(66)90172-2. [DOI] [PubMed] [Google Scholar]
- Moravec J., Corsin A., Owen P., Opie L. H. Effect of increased aortic perfusion pressure on fluorescent emission of the isolated rat heart. J Mol Cell Cardiol. 1974 Apr;6(2):187–200. doi: 10.1016/0022-2828(74)90021-2. [DOI] [PubMed] [Google Scholar]
- Neely J. R., Liebermeister H., Battersby E. J., Morgan H. E. Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol. 1967 Apr;212(4):804–814. doi: 10.1152/ajplegacy.1967.212.4.804. [DOI] [PubMed] [Google Scholar]
- Neely J. R., Rovetto M. J., Oram J. F. Myocardial utilization of carbohydrate and lipids. Prog Cardiovasc Dis. 1972 Nov-Dec;15(3):289–329. doi: 10.1016/0033-0620(72)90029-1. [DOI] [PubMed] [Google Scholar]
- Olson M. S., Williamson J. R. Regulation of citrate synthesis in isolated rat liver mitochondria. J Biol Chem. 1971 Dec 25;246(24):7794–7803. [PubMed] [Google Scholar]
- Opie L. H. Coronary flow rate and perfusion pressure as determinants of mechanical function and oxidative metabolism of isolated perfused rat heart. J Physiol. 1965 Oct;180(3):529–541. doi: 10.1113/jphysiol.1965.sp007715. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Opie L. H., Mansford K. R., Owen P. Effects of increased heart work on glycolysis and adenine nucleotides in the perfused heart of normal and diabetic rats. Biochem J. 1971 Sep;124(3):475–490. doi: 10.1042/bj1240475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Opie L. H. Metabolism of the heart in health and disease. I. Am Heart J. 1968 Nov;76(5):685–698. doi: 10.1016/0002-8703(68)90168-3. [DOI] [PubMed] [Google Scholar]
- Opie L. H., Owen P., Mansford K. R. Metabolic adjustments to acute heart work: observations in the isolated perfused rat heart. Cardiovasc Res. 1971 Jul;Suppl 1:87–95. doi: 10.1093/cvr/5.supp1.87. [DOI] [PubMed] [Google Scholar]
- Opie L. H., Owen P., Thomas M., Samson R. Coronary sinus lactate measurements in assessment of myocardial ischemia. Comparison with changes in lactate-pyruvate and beta-hydroxybutyrate-acetoacetate ratios and with release of hydrogen, phosphate and potassium ions from the heart. Am J Cardiol. 1973 Sep 7;32(3):295–305. doi: 10.1016/s0002-9149(73)80137-7. [DOI] [PubMed] [Google Scholar]
- Owen O. E., Markus H., Sarshik S., Mozzoli M. Relationship between plasma and muscle concentrations of ketone bodies and free fatty acids in fed, starved and alloxan-diabetic states. Biochem J. 1973 Jun;134(2):499–506. doi: 10.1042/bj1340499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Randle P. J., England P. J., Denton R. M. Control of the tricarboxylate cycle and its interactions with glycolysis during acetate utilization in rat heart. Biochem J. 1970 May;117(4):677–695. doi: 10.1042/bj1170677. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rognstad R., Katz J. Malate exchange between the cytosol and mitochondria. Biochem J. 1973 Feb;132(2):349–352. doi: 10.1042/bj1320349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SERAYDARIAN K., MOMMAERTS W. F., WALLNER A., GUILLORY R. J. An estimation of the true inorganic phosphate content of frog sartorius muscle. J Biol Chem. 1961 Jul;236:2071–2075. [PubMed] [Google Scholar]
- Scholz R., Thurman R. G., Williamson J. R., Chance B., Bücher T. Flavin and pyridine nucleotide oxidation-reduction changes in perfused rat liver. I. Anoxia and subcellular localization of fluorescent flavoproteins. J Biol Chem. 1969 May 10;244(9):2317–2324. [PubMed] [Google Scholar]
- Smith Colleen M., Williamson John R. Inhibition of citrate synthase by succinyl-CoA and other metabolites. FEBS Lett. 1971 Oct 15;18(1):35–38. doi: 10.1016/0014-5793(71)80400-3. [DOI] [PubMed] [Google Scholar]
- Srere P. A., Matsuoka Y. Inhibition of rat citrate synthase by acetoacetyl CoA and NADH. Biochem Med. 1972 Jun;6(3):262–266. doi: 10.1016/0006-2944(72)90047-6. [DOI] [PubMed] [Google Scholar]
- WIELAND O., WEISS L. INHIBITION OF CITRATE-SYNTHASE BY PALMITYL-COENZYME A. Biochem Biophys Res Commun. 1963 Sep 10;13:26–31. doi: 10.1016/0006-291x(63)90156-6. [DOI] [PubMed] [Google Scholar]
- WILLIAMSON D. H., MELLANBY J., KREBS H. A. Enzymic determination of D(-)-beta-hydroxybutyric acid and acetoacetic acid in blood. Biochem J. 1962 Jan;82:90–96. doi: 10.1042/bj0820090. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WILLIAMSON J. R., KREBS H. A. Acetoacetate as fuel of respiration in the perfused rat heart. Biochem J. 1961 Sep;80:540–547. doi: 10.1042/bj0800540. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WOLLENBERGER A., RISTAU O., SCHOFFA G. [A simple technic for extremely rapid freezing of large pieces of tissue]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1960;270:399–412. [PubMed] [Google Scholar]
- Whereat A. F., Chan A. Effects of hypoxemia and acute coronary occlusion on myocardial metabolism in dogs. Am J Physiol. 1972 Dec;223(6):1398–1406. doi: 10.1152/ajplegacy.1972.223.6.1398. [DOI] [PubMed] [Google Scholar]
- Williamson D. H., Lund P., Krebs H. A. The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem J. 1967 May;103(2):514–527. doi: 10.1042/bj1030514. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wright J. A., Sanwal B. D. Regulatory mechanisms involving nicotinamide adenine nucleotides as allosteric effectors. IV. Physicochemical study and binding of ligands to citrate synthase. J Biol Chem. 1971 Mar 25;246(6):1689–1699. [PubMed] [Google Scholar]