___________________
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Amino Acid Metabolism, Muscular Fatigue and Muscle Wasting Speculations on Adaptations at High Altitude A. J. M. Wagenmakers Department of Human Biology, University of Limburg, Maastricht, The Netherlands
Abstract A. J. M. Wagenmakers, Amino Acid Metabolism, Muscular Fatigue and Muscle Wasting. Speculations on Adaptations at High Altitude. mt j Sports Med, Vol 13, Suppll,ppSllO—5113, 1992.
Recent investigations from our and other laboratories indicate that glycogen is a carbon-chain precursor in muscle for the synthesis of TCA cycle intermediates and glutamine. During intense exercise and in conditions of a relative lack of energy (hypoxia, trauma, sepsis) the metabolism of branched-chain amino acids (BCAA) is accelerated in muscle. In the primary BCAA aminotransferase reaction 2-oxoglutarate is used as aminogroup acceptor (putting a carbon-drain on the TCA cycle)
under formation of glutamate. Glutamate will subsequently react with ammonia, generated in the AMP deami-
lnt.J.SportsMed. 13(1992)S1lO—S113 GeorgThieme Verlag StuttgartNew York
nase reaction or by deamination of amino acids, under formation of glutamine in a reaction catalysed by glutamine synthetase (glutamate + ammonia + ATP ----> glutamine
+ ADP). Muscle glycogen stores may be smaller or less available at high altitude. It is hypothesized that this will lead to premature fatigue (due to both a lack of fuel and of TCA cycle carbon-precursor) and to a reduction in the synthesis rate of glutamine. A chronic reduction in the synthesis rate of glutamine during a long term stay at high altitude on its turn may lead to gut atrophy, bacterial translocation, endotoxemia, muscle protein catabolism and a weakened immune status. Key words
Muscle metabolism, exercise, amino acids, glutamine, protein catabolism
Downloaded by: Universite de Sherbrooke. Copyrighted material.
SIlO Int.J.SportsMed. 13 (1992)
mt. J. Sports Med.13 13(1992) Int.J.SportsMed. (1992) Sill
Amino Acid Metabolism, Muscular Fatigue and Muscle Wasting
Introduction Lowlanders who ascend to high altitude have a reduced physical work capacity and reduced endurance at a given workload. During a more prolonged stay at heights < 5000 mmacclimatization 20% to the plasma amino acid pool. The question could be asked why is the synthesis rate of glutamine so high and why are intra- and extra-
cellular concentrations of this non-essential amino acid so high. Sir Hans Krebs (8) has been the first to suggest that glutamine has to be synthesized at such a high rate because of the numerous important functions of glutamine in intermediary metabolism. Glutamine among others is 1. the most important vehicle for the transfer of nitrogen between organs (it trans-
ports ammonia in a non-toxic form), 2. the most important substrate substrate for renal ammoniagenesis, a role that is linked linked to to the the maintenance of acid-base balance during acidosis and starva-
tion, 3. an essentiai nitrogen precursor for the synthesis of purine and pyrimidine nucleotides, 4. an excellent fuel for gut mucosal cells (21) and cells of the immune system (in fact for all rapidly dividing cells), 5. potentially a direct regulator of
muscle protein synthesis and degradation (10, 11). During stress states skeletal muscle releases large amounts of ginglutamine and eventually the muscle and plasma glutamine stores become depleted (9, 16). 16). It It has has been been suggested suggested that that aa relative relative glutamine deficiency is a cause of gut atrophy in patients with sepsis and trauma. Gut atrophy on its turn may lead to bacte-
rial translocation, entry of bacteria and endotoxins in the circulation and production of cytokines and interleukins. These compounds will activate the synthesis of acute phase proteins in the liver and will induce net protein catabolism in skeletal muscle. This mechanism may contribute to the rapid breakdown of muscle mass in critically-ill patients (upto 15 kg in in 22 weeks). weeks). Endotoxemia Endotoxemia may may further further enhance enhance the the loss loss of of gluglutamine from skeletal muscle and further deplete the glutamine stores of the human body, thus leading to a self-propagating irreversible series of events often ending with death. Endotoxemia also has been implicated in the development of oedema, adult adult respiratory respiratory distress distress syndrome syndrome and and multiple multiple organ organ failure failure (MOF) in critically ill patients. A relative lack of glutamine also leads to an impairment of the immune system in these patients (9, 16), probably due to the fact that glutamine is a fuel
for immune system cells and a regulator of purine and pyrimidine synthesis. Several studies have suggested that provision of exogenous glutamine attenuates muscle wasting and enhances nitrogen balance in critically-ill patients (9, 16), implying that glutamine may be a conditionally essential amino acid that has to be added to human nutrition in certain certain stress stress situations.
Amino Acid Metabolism at High Altitude Very little is known about the metabolism of amino acids at high altitude. During the first days at high altitude the catecholamine levels are increased (22) and lead to excessive rates of anaerobic glycolysis during low intensity exercise and sometimes even at rest. This could deplete the glyco-
gen stores and contribute to to premature premature fatigue fatigue due due to to 1. 1 reduced availability of glycogen as a fuel and 2. reduced synthesis rates of TCA cycle intermediates and excessive activation of BCAA metabolism. It also could lead to reduced synthesis rates of giutamine. glutamine. However, at heights below 5000 m acclimatization will will occur occur and and after after 22 weeks weeks at at this this altitude altitude glycogen glycogen tization stores stores are are completely completely full full again again (7). (7). A A blunted blunted lactate lactate response response in in blood blood and and muscle muscle occurs occurs at at that that point point in in time time and and may may indiindi-
cate that the glycogen stores are not adequately mobilised during exercise. exercise. This This again again could could imply imply that that synthesis synthesis rates rates of of during TCA cycle intermediates and glutamine are reduced. A rapid continuous loss of skeletal muscle mass occurs at very high altitudes (> 6000 m). It is tempting tempting to to speculate speculate that that chronically chronically increased catecholamine levels and hypoxic stress at these altitudes lead to a reduction in the size of the muscle glycogen pools and a reduction in the rate of synthesis of TCA cycle intermediates and glutamine. Furthermore, low intensity exercise at these altitudes may lead to large losses of glutamine from muscle (possibly due to the fact that the sodium gradient cannot be maintained) and eventually may lead to a reduction in in the the size size of of the the glutamine glutamine pools. pools. This This may may activate activate the the same same sequence of events described above for patients with trauma and sepsis and could explain the inability of mountaineers mountaineers to to curtail curtail muscle muscle protein protein wasting wasting at at very very high high altitudes, altitudes. It It also also is is tempting to speculate that this series of events plays a role in the development of oedema (14) and in the general deterioration of immune function and health. References Elia M., Livesey G.: Effect of ingested steak and infused leucine on forelimb metabolism in man and the fate of the carbon skeletons and amino groups of branched-chain amino acids. C/in Sci 64: 517— 526, 1983. 517—526,1983.
Downloaded by: Universite de Sherbrooke. Copyrighted material.
duction, loss of part of the large muscle store, or a combination of both. Rennie et al. (12) observed a reduction of the muscular glutamine pool to about half the preexercise value following 4 h of exercise at 50% VO2max. During prolonged intense exer-
Amino A cid Metabolism, Metabolism, Muscular Muscular Fatigue and Muscle Wasting Acid
(1992) S113 mt. J. Sports Sports Med. Med. 13 13(1992)
ErikssonL. 14 Richalet Richalet J.-P., 22 Eriksson Björkman 0., 0., Wahren J.: Ammonia me- me-14 L.S., S.,Broberg BrobergS.,S., Björkman Wahren J.: Ammonia J.-P., Rathat Rathat C., C., Keromes Keromes A., A., Herry Herry J.-P., J.-P., Larmignat Larmignat P., P., tabolism during during exercise exercise in in man. man. Cliii Clin Physiol5: Physiols: 325—336, 1985. tabolism Gamier M., Pilardeau P.: Plasma volume, body weight, and acute Felig P.: Amino acid metabolism in man. Annu Rev Biochem Biochein 44: mountain sickness. Lancet I: 525, 1983. b15 Sahlin Sahlin K., intermedi933—955,1975. 933—955,1975. K., Katz Katz A., Broberg S.: Tricarboxylic acid cycle intermediW.: Regulation Regulationand andsignificance significanceofof ates in human muscle during prolonged exercise. Am J Physiol Goldberg A. L., Chang T. W.: Goldberg amino acid metabolism metabolism in in skeletal skeletal muscle. muscle. Fed Fed Proc Proc37: 37:230 2301— 1— 259: C834—C841, 1990. 16 Souba Souba W. W. W.: W.: Glutamine: Glutamine: aa key key substrate substrate for for the the splanchnic splanchnic bed. bed. 2307, 2307, 1978. AnnuRevNutr 11:285—308, 1991. Golden M. H. N., Jahoor P., Jackson A. A.: Glutamine production AnnuRevNutr 11:285—308,1991. 17 17 Wagenmakers A.J.J.M.: M.:Role Role of of amino amino acids acids and and ammonia ammonia in rate and its contribution contribution to to urinary urinary ammonia ammonia in in normal normalman. man.Cliii Clin Wagenmakers A. mechanisms of fatigue, in Marconnet P., Komi P., Saltin B. (eds): 1982. Sciô2:299—305, 1982. Sc162:299—305, 6 Local Fatigue in Exercise and Training. Karger Series on Med Green H. J., Sutton J. R., Cymerman A., Young P. Green P. M., M., Houston Houston C. C. S.: Operation Everest II: adaptations in human skeletal muscle. J Sport Sci 34: pp 69—86,1992. 2454—2461, 1989. Wagenmakers A. J. M., Beckers E., Brouns F., Kuipers H., Soeters ApplPhysiol66: 1989. ApplPhysiol66:2454—2461, P. B., van der Vusse G. J., Saris W. H. M.: Carbohydrate supGreen H. J., Sutton J., Young P., Cymerman A., Houston C. S.: plementation, glycogen depletion, and amino acid metabolism Operation Everest 11: H: muscle muscle energetics energetics during maximal exhausduring exercise. Am JJPhysiol26O: Physiol 260: E883—E890, E883—E890, 1991. tive exercise. 66: 142—150, 1989. exercise, JAppiPhysiol JApplPhysiol66: 8 H.A.: A.:Glutamine Glutaminemetabolism metabolism in in the the animal animal body, body, in Mora 0 Krebs Krebs H. ' Wagenmakers A.A.J. J.M., Wagenmakers M.,Brookes BrookesJ.J.H., H.,Coakley CoakleyJ.J.H., H., Reilly Reilly T., T., Edwards R. H. T.: Exercise-induced activation of the branched-chain J., Palacios R. (eds): Glutamine: Metabolism, Enzymology, and 2-oxo acid dehydrogenase dehydrogenase in in human human skeletal skeletal muscle. muscle.Eur EurJJAppi App! Regulation. 1980, pp pp 319—329. 319—329. Regulation. New York, Academic Press, 1980, Lacey J. M., Wilmore D. W.: Is glutamine a conditionally essential Physiol59: 159—167,1989. Physiols9: 20 A.J.J.M., M., Coakley Coakley J.J. H., H., Edwards Edwards R. H. T.: Metabo20 Wagenmakers amino acid? acid?NutrRev NutrRev48: 48: 297—309, 297—309,1990. 1990. WagenmakersA. lism of branched-chain amino acids and ammonia during exerMacLennan P. A., Brown R. A., Rennie M. J.: A positive 10 MacLennan positive relationrelationcise: Clues Clues from fromMcArdle's McArdle'sdisease. disease.mt utJJSports SportsMed Med11: 11:SSlOl— 101— ship between protein synthetic rate and intracellular glutamine S113, 1990. concentration in perfused perfused rat rat skeletal skeletal muscle. muscle. FEBSLeII FEBSLet 215: 215: 187— 2! 2! Windmueller Windmueller H. H.G., G.,Spaeth SpaethA. A.E.: E.:Respiratory Respiratoryfuels fuelsand andnitrogen nitrogen 191 1987. 191,1987. metabolism in vivo in small intestine of fed rats. JBiol Chem 255: l MacLennan MacLennanP.P.A., A.,Smith SmithK., K.,Weryk Weryk B., B., Rennie Rennie M. J.: Inhibition of of protein breakdown by glutamine in perfused rat skeletal muscle. 107—112,1980. 22 22 Young A.: Energy Energy substrate substrate utilization utilization during during exercise exercise in in extreme extreme FEBSLett237: 1988. YoungA.: FEBSLett237: 133—136, 133—136,1988. 22 Rennie Exere Sport SciRev 18:65—118, 1990. environments. Exerc M.J., J.,Edwards EdwardsR. R. H. H. T., T., Krywawych Krywawych S., Davies C. T. T. M., M., RennieM. Halliday D., Waterlow J. C., Millward D. J.: Effect of exercise on proteinturnoverinman.ClinSci6l:627—639, 1981. Anton J. Mi M Wagenmakers, Wagenmakers, Ph. D. Rennie M. J., Hundal H. S., Babij P., MacLennan P. A., Taylor P. M., Watt P. W., Jepson M. M., Millward D. J.: Characteristics of a Department of Human Biology glutamine carrier in skeletal muscle have important consequences University of Limburg Limburg for nitrogen loss in injury, infection and chronic disease. Lancet II: P.O. P.O. Box 616 1008— 1012, 1986. 6200 MD Maastricht The Netherlands
Downloaded by: Universite de Sherbrooke. Copyrighted material.
'
________
Amino Acid Metabolism, Muscular Fatigue and Muscle Wasting Speculations on Adaptations at High Altitude A. J. M. Wagenmakers Department of Human Biology, University of Limburg, Maastricht, The Netherlands
Abstract A. J. M. Wagenmakers, Amino Acid Metabolism, Muscular Fatigue and Muscle Wasting. Speculations on Adaptations at High Altitude. mt j Sports Med, Vol 13, Suppll,ppSllO—5113, 1992.
Recent investigations from our and other laboratories indicate that glycogen is a carbon-chain precursor in muscle for the synthesis of TCA cycle intermediates and glutamine. During intense exercise and in conditions of a relative lack of energy (hypoxia, trauma, sepsis) the metabolism of branched-chain amino acids (BCAA) is accelerated in muscle. In the primary BCAA aminotransferase reaction 2-oxoglutarate is used as aminogroup acceptor (putting a carbon-drain on the TCA cycle)
under formation of glutamate. Glutamate will subsequently react with ammonia, generated in the AMP deami-
lnt.J.SportsMed. 13(1992)S1lO—S113 GeorgThieme Verlag StuttgartNew York
nase reaction or by deamination of amino acids, under formation of glutamine in a reaction catalysed by glutamine synthetase (glutamate + ammonia + ATP ----> glutamine
+ ADP). Muscle glycogen stores may be smaller or less available at high altitude. It is hypothesized that this will lead to premature fatigue (due to both a lack of fuel and of TCA cycle carbon-precursor) and to a reduction in the synthesis rate of glutamine. A chronic reduction in the synthesis rate of glutamine during a long term stay at high altitude on its turn may lead to gut atrophy, bacterial translocation, endotoxemia, muscle protein catabolism and a weakened immune status. Key words
Muscle metabolism, exercise, amino acids, glutamine, protein catabolism
Downloaded by: Universite de Sherbrooke. Copyrighted material.
SIlO Int.J.SportsMed. 13 (1992)
mt. J. Sports Med.13 13(1992) Int.J.SportsMed. (1992) Sill
Amino Acid Metabolism, Muscular Fatigue and Muscle Wasting
Introduction Lowlanders who ascend to high altitude have a reduced physical work capacity and reduced endurance at a given workload. During a more prolonged stay at heights < 5000 mmacclimatization 20% to the plasma amino acid pool. The question could be asked why is the synthesis rate of glutamine so high and why are intra- and extra-
cellular concentrations of this non-essential amino acid so high. Sir Hans Krebs (8) has been the first to suggest that glutamine has to be synthesized at such a high rate because of the numerous important functions of glutamine in intermediary metabolism. Glutamine among others is 1. the most important vehicle for the transfer of nitrogen between organs (it trans-
ports ammonia in a non-toxic form), 2. the most important substrate substrate for renal ammoniagenesis, a role that is linked linked to to the the maintenance of acid-base balance during acidosis and starva-
tion, 3. an essentiai nitrogen precursor for the synthesis of purine and pyrimidine nucleotides, 4. an excellent fuel for gut mucosal cells (21) and cells of the immune system (in fact for all rapidly dividing cells), 5. potentially a direct regulator of
muscle protein synthesis and degradation (10, 11). During stress states skeletal muscle releases large amounts of ginglutamine and eventually the muscle and plasma glutamine stores become depleted (9, 16). 16). It It has has been been suggested suggested that that aa relative relative glutamine deficiency is a cause of gut atrophy in patients with sepsis and trauma. Gut atrophy on its turn may lead to bacte-
rial translocation, entry of bacteria and endotoxins in the circulation and production of cytokines and interleukins. These compounds will activate the synthesis of acute phase proteins in the liver and will induce net protein catabolism in skeletal muscle. This mechanism may contribute to the rapid breakdown of muscle mass in critically-ill patients (upto 15 kg in in 22 weeks). weeks). Endotoxemia Endotoxemia may may further further enhance enhance the the loss loss of of gluglutamine from skeletal muscle and further deplete the glutamine stores of the human body, thus leading to a self-propagating irreversible series of events often ending with death. Endotoxemia also has been implicated in the development of oedema, adult adult respiratory respiratory distress distress syndrome syndrome and and multiple multiple organ organ failure failure (MOF) in critically ill patients. A relative lack of glutamine also leads to an impairment of the immune system in these patients (9, 16), probably due to the fact that glutamine is a fuel
for immune system cells and a regulator of purine and pyrimidine synthesis. Several studies have suggested that provision of exogenous glutamine attenuates muscle wasting and enhances nitrogen balance in critically-ill patients (9, 16), implying that glutamine may be a conditionally essential amino acid that has to be added to human nutrition in certain certain stress stress situations.
Amino Acid Metabolism at High Altitude Very little is known about the metabolism of amino acids at high altitude. During the first days at high altitude the catecholamine levels are increased (22) and lead to excessive rates of anaerobic glycolysis during low intensity exercise and sometimes even at rest. This could deplete the glyco-
gen stores and contribute to to premature premature fatigue fatigue due due to to 1. 1 reduced availability of glycogen as a fuel and 2. reduced synthesis rates of TCA cycle intermediates and excessive activation of BCAA metabolism. It also could lead to reduced synthesis rates of giutamine. glutamine. However, at heights below 5000 m acclimatization will will occur occur and and after after 22 weeks weeks at at this this altitude altitude glycogen glycogen tization stores stores are are completely completely full full again again (7). (7). A A blunted blunted lactate lactate response response in in blood blood and and muscle muscle occurs occurs at at that that point point in in time time and and may may indiindi-
cate that the glycogen stores are not adequately mobilised during exercise. exercise. This This again again could could imply imply that that synthesis synthesis rates rates of of during TCA cycle intermediates and glutamine are reduced. A rapid continuous loss of skeletal muscle mass occurs at very high altitudes (> 6000 m). It is tempting tempting to to speculate speculate that that chronically chronically increased catecholamine levels and hypoxic stress at these altitudes lead to a reduction in the size of the muscle glycogen pools and a reduction in the rate of synthesis of TCA cycle intermediates and glutamine. Furthermore, low intensity exercise at these altitudes may lead to large losses of glutamine from muscle (possibly due to the fact that the sodium gradient cannot be maintained) and eventually may lead to a reduction in in the the size size of of the the glutamine glutamine pools. pools. This This may may activate activate the the same same sequence of events described above for patients with trauma and sepsis and could explain the inability of mountaineers mountaineers to to curtail curtail muscle muscle protein protein wasting wasting at at very very high high altitudes, altitudes. It It also also is is tempting to speculate that this series of events plays a role in the development of oedema (14) and in the general deterioration of immune function and health. References Elia M., Livesey G.: Effect of ingested steak and infused leucine on forelimb metabolism in man and the fate of the carbon skeletons and amino groups of branched-chain amino acids. C/in Sci 64: 517— 526, 1983. 517—526,1983.
Downloaded by: Universite de Sherbrooke. Copyrighted material.
duction, loss of part of the large muscle store, or a combination of both. Rennie et al. (12) observed a reduction of the muscular glutamine pool to about half the preexercise value following 4 h of exercise at 50% VO2max. During prolonged intense exer-
Amino A cid Metabolism, Metabolism, Muscular Muscular Fatigue and Muscle Wasting Acid
(1992) S113 mt. J. Sports Sports Med. Med. 13 13(1992)
ErikssonL. 14 Richalet Richalet J.-P., 22 Eriksson Björkman 0., 0., Wahren J.: Ammonia me- me-14 L.S., S.,Broberg BrobergS.,S., Björkman Wahren J.: Ammonia J.-P., Rathat Rathat C., C., Keromes Keromes A., A., Herry Herry J.-P., J.-P., Larmignat Larmignat P., P., tabolism during during exercise exercise in in man. man. Cliii Clin Physiol5: Physiols: 325—336, 1985. tabolism Gamier M., Pilardeau P.: Plasma volume, body weight, and acute Felig P.: Amino acid metabolism in man. Annu Rev Biochem Biochein 44: mountain sickness. Lancet I: 525, 1983. b15 Sahlin Sahlin K., intermedi933—955,1975. 933—955,1975. K., Katz Katz A., Broberg S.: Tricarboxylic acid cycle intermediW.: Regulation Regulationand andsignificance significanceofof ates in human muscle during prolonged exercise. Am J Physiol Goldberg A. L., Chang T. W.: Goldberg amino acid metabolism metabolism in in skeletal skeletal muscle. muscle. Fed Fed Proc Proc37: 37:230 2301— 1— 259: C834—C841, 1990. 16 Souba Souba W. W. W.: W.: Glutamine: Glutamine: aa key key substrate substrate for for the the splanchnic splanchnic bed. bed. 2307, 2307, 1978. AnnuRevNutr 11:285—308, 1991. Golden M. H. N., Jahoor P., Jackson A. A.: Glutamine production AnnuRevNutr 11:285—308,1991. 17 17 Wagenmakers A.J.J.M.: M.:Role Role of of amino amino acids acids and and ammonia ammonia in rate and its contribution contribution to to urinary urinary ammonia ammonia in in normal normalman. man.Cliii Clin Wagenmakers A. mechanisms of fatigue, in Marconnet P., Komi P., Saltin B. (eds): 1982. Sciô2:299—305, 1982. Sc162:299—305, 6 Local Fatigue in Exercise and Training. Karger Series on Med Green H. J., Sutton J. R., Cymerman A., Young P. Green P. M., M., Houston Houston C. C. S.: Operation Everest II: adaptations in human skeletal muscle. J Sport Sci 34: pp 69—86,1992. 2454—2461, 1989. Wagenmakers A. J. M., Beckers E., Brouns F., Kuipers H., Soeters ApplPhysiol66: 1989. ApplPhysiol66:2454—2461, P. B., van der Vusse G. J., Saris W. H. M.: Carbohydrate supGreen H. J., Sutton J., Young P., Cymerman A., Houston C. S.: plementation, glycogen depletion, and amino acid metabolism Operation Everest 11: H: muscle muscle energetics energetics during maximal exhausduring exercise. Am JJPhysiol26O: Physiol 260: E883—E890, E883—E890, 1991. tive exercise. 66: 142—150, 1989. exercise, JAppiPhysiol JApplPhysiol66: 8 H.A.: A.:Glutamine Glutaminemetabolism metabolism in in the the animal animal body, body, in Mora 0 Krebs Krebs H. ' Wagenmakers A.A.J. J.M., Wagenmakers M.,Brookes BrookesJ.J.H., H.,Coakley CoakleyJ.J.H., H., Reilly Reilly T., T., Edwards R. H. T.: Exercise-induced activation of the branched-chain J., Palacios R. (eds): Glutamine: Metabolism, Enzymology, and 2-oxo acid dehydrogenase dehydrogenase in in human human skeletal skeletal muscle. muscle.Eur EurJJAppi App! Regulation. 1980, pp pp 319—329. 319—329. Regulation. New York, Academic Press, 1980, Lacey J. M., Wilmore D. W.: Is glutamine a conditionally essential Physiol59: 159—167,1989. Physiols9: 20 A.J.J.M., M., Coakley Coakley J.J. H., H., Edwards Edwards R. H. T.: Metabo20 Wagenmakers amino acid? acid?NutrRev NutrRev48: 48: 297—309, 297—309,1990. 1990. WagenmakersA. lism of branched-chain amino acids and ammonia during exerMacLennan P. A., Brown R. A., Rennie M. J.: A positive 10 MacLennan positive relationrelationcise: Clues Clues from fromMcArdle's McArdle'sdisease. disease.mt utJJSports SportsMed Med11: 11:SSlOl— 101— ship between protein synthetic rate and intracellular glutamine S113, 1990. concentration in perfused perfused rat rat skeletal skeletal muscle. muscle. FEBSLeII FEBSLet 215: 215: 187— 2! 2! Windmueller Windmueller H. H.G., G.,Spaeth SpaethA. A.E.: E.:Respiratory Respiratoryfuels fuelsand andnitrogen nitrogen 191 1987. 191,1987. metabolism in vivo in small intestine of fed rats. JBiol Chem 255: l MacLennan MacLennanP.P.A., A.,Smith SmithK., K.,Weryk Weryk B., B., Rennie Rennie M. J.: Inhibition of of protein breakdown by glutamine in perfused rat skeletal muscle. 107—112,1980. 22 22 Young A.: Energy Energy substrate substrate utilization utilization during during exercise exercise in in extreme extreme FEBSLett237: 1988. YoungA.: FEBSLett237: 133—136, 133—136,1988. 22 Rennie Exere Sport SciRev 18:65—118, 1990. environments. Exerc M.J., J.,Edwards EdwardsR. R. H. H. T., T., Krywawych Krywawych S., Davies C. T. T. M., M., RennieM. Halliday D., Waterlow J. C., Millward D. J.: Effect of exercise on proteinturnoverinman.ClinSci6l:627—639, 1981. Anton J. Mi M Wagenmakers, Wagenmakers, Ph. D. Rennie M. J., Hundal H. S., Babij P., MacLennan P. A., Taylor P. M., Watt P. W., Jepson M. M., Millward D. J.: Characteristics of a Department of Human Biology glutamine carrier in skeletal muscle have important consequences University of Limburg Limburg for nitrogen loss in injury, infection and chronic disease. Lancet II: P.O. P.O. Box 616 1008— 1012, 1986. 6200 MD Maastricht The Netherlands
Downloaded by: Universite de Sherbrooke. Copyrighted material.
'
