Effect of exercise on hexokinase distribution and mitochondrial respiration in skeletal muscle.
Abstract: Horses were subjected to treadmill running at 65% (submaximal) or 100% (maximal) VO2,max to examine the effects of exercise on subcellular distribution of hexokinase (HK) and on mitochondrial respiration. It is hypothesized that the fraction of HK bound to mitochondria will be reduced due to an elevation of glucose-6-phosphate (G-6-P) concentration in the exercising muscle and that such release of HK from mitochondria will depress oxidative phosphorylation. Changes in muscle G-6-P concentration, pH, subcellular HK distribution, mitochondrial respiration and other metabolites were determined in biopsy samples pre-exercise, immediately post-exercise and during the recovery phase. The fraction of HK associated with mitochondria decreased from 38% to 7% at the end of maximal exercise; exercise at VO2,max also reduced respiratory capacity of muscle homogenates by 20% and was associated with a fivefold increase in muscle [G-6-P], a potent agent known to dissociate HK from mitochondria. The HK distribution returned to normal within 60 min after exercise and the reassociation of the HK with mitochondria parallelled the removal of muscle G-6-P. No changes in muscle HK distribution and respiration were found following the submaximal exercise despite the fact that G-6-P was slightly elevated. Muscle concentrations of adenosine triphosphate, creatine phosphate and glycogen and pH dropped after exercise while lactate concentration increased. The amount of mitochondria-bound HK was also altered in vitro in a preparation of mitochondria isolated from rat skeletal muscle to examine the effect of the bound HK on mitochondrial respiration.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Date: 1994-06-01 PubMed ID: 8072844DOI: 10.1007/BF00374532Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research demonstrates that intense exercise in horses causes a significant decrease in the amount of the enzyme hexokinase associated with muscle mitochondria, and a corresponding decrease in respiratory capacity of the muscle tissue. The result is influenced by the concurrent massive increase in the concentration of glucose-6-phosphate in the working muscles.
Objective and Methodology
- The research focuses on understanding the effects of exercise at various intensities on the enzyme hexokinase’s subcellular distribution and the mitochondrial respiration in the skeletal muscle of horses.
- The horses were made to run on a treadmill at 65% (submaximal) and 100% (maximal) of their maximum oxygen uptake (VO2,max) capacities.
- The researchers hypothesized that the undergoing exercise would cause a reduced fraction of hexokinase bound to the mitochondria due to high glucose-6-phosphate (G-6-P) concentration in the exercising muscles, thereby depressing oxidative phosphorylation.
Findings
- Exercise resulted in changes in muscle G-6-P concentration, pH, hexokinase distribution, mitochondrial respiration, and other metabolites. These changes were measured using biopsy samples pre, post, and during recovery from exercise.
- Maximal exercise led to a decrease in the proportion of hexokinase associated with mitochondria from 38% to 7% and a 20% reduction in the muscle tissues’ respiratory capacity. They also noticed a fivefold increase in muscle glucose-6-phosphate levels, which is known to dissociate hexokinase from the mitochondria.
- The distribution of hexokinase returned to normal within 60 minutes after exercise in correlation with the reduction of muscle glucose-6-phosphate.
- Mild exercise didn’t exhibit any changes in hexokinase distribution and mitochondrial respiration, although glucose-6-phosphate was slightly elevated.
- Muscle concentrations of adenosine triphosphate, creatine phosphate, and glycogen dropped post-exercise, and the pH and lactate concentration increased.
- In vitro studies on isolated rat skeletal muscle mitochondria showed changes in the amount of mitochondria-bound hexokinase, examining its effect on mitochondrial respiration.
Conclusion
- Essentially, the research study concluded that increased exercise intensity results in a decrease in the amount of the enzyme hexokinase bound to muscle mitochondria and decreases the respiratory capacity of the muscle tissue. The primary influential factor for this change was the increase in the concentration of glucose-6-phosphate in the working muscles.
Cite This Article
APA
Chen J, Gollnick PD.
(1994).
Effect of exercise on hexokinase distribution and mitochondrial respiration in skeletal muscle.
Pflugers Arch, 427(3-4), 257-263.
https://doi.org/10.1007/BF00374532 Publication
Researcher Affiliations
- Department of Veterinary and Comparative Anatomy, Pharmacology, College of Veterinary Medicine, Pullman, WA 99164-6520.
MeSH Terms
- Adenosine Triphosphate / metabolism
- Animals
- Glucose-6-Phosphate
- Glucosephosphates / metabolism
- Glycogen / metabolism
- Hexokinase / metabolism
- Horses
- Hydrogen-Ion Concentration
- Lactates / metabolism
- Lactic Acid
- Magnesium / physiology
- Male
- Mitochondria, Muscle / drug effects
- Mitochondria, Muscle / enzymology
- Mitochondria, Muscle / metabolism
- Oxygen Consumption
- Phosphocreatine / metabolism
- Physical Exertion / physiology
- Rats
- Rats, Sprague-Dawley
References
This article includes 33 references
- Adams V, Griffin L, Towbin J, Gelb B, Worley K, McCabe ER. Porin interaction with hexokinase and glycerol kinase: metabolic microcompartmentation at the outer mitochondrial membrane.. Biochem Med Metab Biol 1991 Jun;45(3):271-91.
- Felgner PL, Messer JL, Wilson JE. Purification of a hexokinase-binding protein from the outer mitochondrial membrane.. J Biol Chem 1979 Jun 25;254(12):4946-9.
- Gollnick PD, Bertocci LA, Kelso TB, Witt EH, Hodgson DR. The effect of high-intensity exercise on the respiratory capacity of skeletal muscle.. Pflugers Arch 1990 Jan;415(4):407-13.
- Bessman SP, Carpenter CL. The creatine-creatine phosphate energy shuttle.. Annu Rev Biochem 1985;54:831-62.
- Goncharova NIu, Zelenina EV. [The effect of insulin on the catalytic efficacy of rat skeletal muscle hexokinase isoenzyme II].. Biokhimiia 1991 May;56(5):913-22.
- Warhol MJ, Siegel AJ, Evans WJ, Silverman LM. Skeletal muscle injury and repair in marathon runners after competition.. Am J Pathol 1985 Feb;118(2):331-9.
- Katz A, Broberg S, Sahlin K, Wahren J. Leg glucose uptake during maximal dynamic exercise in humans.. Am J Physiol 1986 Jul;251(1 Pt 1):E65-70.
- Rose IA, Warms JV. Mitochondrial hexokinase. Release, rebinding, and location.. J Biol Chem 1967 Apr 10;242(7):1635-45.
- KATZEN HM, SODERMAN DD, NITOWSKY HM. KINETIC AND ELECTROPHORETIC EVIDENCE FOR MULTIPLE FORMS OF GLUCOSE-ATP PHOSPHOTRANSFERASE ACTIVITY FROM HUMAN CELL CULTURES AND RAT LIVER.. Biochem Biophys Res Commun 1965 Apr 23;19:377-82.
- Salotra PT, Singh VN. Regulation of glucose metabolism in rat lung: subcellular distribution, isozyme pattern, and kinetic properties of hexokinase.. Arch Biochem Biophys 1982 Jul;216(2):758-64.
- Kelso TB, Hodgson DR, Visscher AR, Gollnick PD. Some properties of different skeletal muscle fiber types: comparison of reference bases.. J Appl Physiol (1985) 1987 Apr;62(4):1436-41.
- Hermansen L, Osnes JB. Blood and muscle pH after maximal exercise in man.. J Appl Physiol 1972 Mar;32(3):304-8.
- Kupriyanov VV, Ya Steinschneider A, Ruuge EK, Kapel'ko VI, Yu Zueva M, Lakomkin VL, Smirnov VN, Saks VA. Regulation of energy flux through the creatine kinase reaction in vitro and in perfused rat heart. 31P-NMR studies.. Biochim Biophys Acta 1984 Dec 11;805(4):319-31.
- Knull HR, Taylor WF, Wells WW. Effects of energy metabolism on in vivo distribution of hexokinase in brain.. J Biol Chem 1973 Aug 10;248(15):5414-7.
- Rose RJ, Hodgson DR, Kelso TB, McCutcheon LJ, Reid TA, Bayly WM, Gollnick PD. Maximum O2 uptake, O2 debt and deficit, and muscle metabolites in Thoroughbred horses.. J Appl Physiol (1985) 1988 Feb;64(2):781-8.
- Nimmo MA, Snow DH. Time course of ultrastructural changes in skeletal muscle after two types of exercise.. J Appl Physiol Respir Environ Exerc Physiol 1982 Apr;52(4):910-3.
- JOHNSON MK. The intracellular distribution of glycolytic and other enzymes in rat-brain homogenates and mitochondrial preparations.. Biochem J 1960 Dec;77(3):610-8.
- Arany I, Ember I, Rády P. Subcellular distribution of hexokinase in leukemic and stimulated lymphoid cells of mice.. Haematologia (Budap) 1988;21(2):109-14.
- Costill DL, Sparks K, Gregor R, Turner C. Muscle glycogen utilization during exhaustive running.. J Appl Physiol 1971 Sep;31(3):353-6.
- Hearse DJ, Tosaki A. Free radicals and calcium: simultaneous interacting triggers as determinants of vulnerability to reperfusion-induced arrhythmias in the rat heart.. J Mol Cell Cardiol 1988 Mar;20(3):213-23.
- Schaper J, Mulch J, Winkler B, Schaper W. Ultrastructural, functional, and biochemical criteria for estimation of reversibility of ischemic injury: a study on the effects of global ischemia on the isolated dog heart.. J Mol Cell Cardiol 1979 Jun;11(6):521-41.
- Davies KJ, Packer L, Brooks GA. Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training.. Arch Biochem Biophys 1981 Jul;209(2):539-54.
- Harken AH. Hydrogen ion concentration and oxygen uptake in an isolated canine hindlimb.. J Appl Physiol 1976 Jan;40(1):1-5.
- BeltrandelRio H, Wilson JE. Hexokinase of rat brain mitochondria: relative importance of adenylate kinase and oxidative phosphorylation as sources of substrate ATP, and interaction with intramitochondrial compartments of ATP and ADP.. Arch Biochem Biophys 1991 Apr;286(1):183-94.
- Gumaa KA, McLean P. A possible interrelationship between binding of hexokinase and the site of ATP formation in Krebs ascites cells.. Biochem Biophys Res Commun 1969 Aug 22;36(5):771-9.
- Russell RR 3rd, Mrus JM, Mommessin JI, Taegtmeyer H. Compartmentation of hexokinase in rat heart. A critical factor for tracer kinetic analysis of myocardial glucose metabolism.. J Clin Invest 1992 Nov;90(5):1972-7.
- ROSE IA, O'CONNELL EL. THE ROLE OF GLUCOSE 6-PHOSPHATE IN THE REGULATION OF GLUCOSE METABOLISM IN HUMAN ERYTHROCYTES.. J Biol Chem 1964 Jan;239:12-7.
- Wilson JE. Brain hexokinase, the prototype ambiquitous enzyme.. Curr Top Cell Regul 1980;16:1-54.
- Brdiczka D, Knoll G, Riesinger I, Weiler U, Klug G, Benz R, Krause J. Microcompartmentation at the mitochondrial surface: its function in metabolic regulation.. Adv Exp Med Biol 1986;194:55-69.
- Barakat HA, Kasperek GJ, Dohm GL, Tapscott EB, Snider RD. Fatty acid oxidation by liver and muscle preparations of exhaustively exercised rats.. Biochem J 1982 Nov 15;208(2):419-24.
- Jacobus WE, Vandegaer KM, Moreadith RW. Aspects of heart respiratory control by the mitochondrial isozyme of creatine kinase.. Adv Exp Med Biol 1986;194:169-91.
- McCutcheon LJ, Byrd SK, Hodgson DR. Ultrastructural changes in skeletal muscle after fatiguing exercise.. J Appl Physiol (1985) 1992 Mar;72(3):1111-7.
- Purich DL, Fromm HJ. The kinetics and regulation of rat brain hexokinase.. J Biol Chem 1971 Jun 10;246(11):3456-63.
Citations
This article has been cited 2 times.- Layec G, Blain GM, Rossman MJ, Park SY, Hart CR, Trinity JD, Gifford JR, Sidhu SK, Weavil JC, Hureau TJ, Amann M, Richardson RS. Acute High-Intensity Exercise Impairs Skeletal Muscle Respiratory Capacity. Med Sci Sports Exerc 2018 Dec;50(12):2409-2417.
- Tonkonogi M, Harris B, Sahlin K. Mitochondrial oxidative function in human saponin-skinned muscle fibres: effects of prolonged exercise. J Physiol 1998 Jul 1;510 ( Pt 1)(Pt 1):279-86.
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