Lactate metabolism: A new paradigm for the third millennium

Journal of Physiology

Volumn 558, Issue 1, 2004, Pages 5-30

  Gladden, L B ^a  

^a AUBURN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; LACTIC ACID; ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); ADENOSINE TRIPHOSPHATE; GLUCOSE; LACTATE DEHYDROGENASE; NICOTINAMIDE ADENINE DINUCLEOTIDE; OXYGEN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE;

AEROBIC METABOLISM; ANAEROBIC METABOLISM; ANOXIA; ASTROCYTE; BRAIN ISCHEMIA; CELL COMPARTMENTALIZATION; CELL METABOLISM; GLYCOLYSIS; HUMAN; LACTIC ACIDOSIS; MUSCLE CONTRACTION; MUSCLE EXERCISE; MUSCLE FATIGUE; MUSCLE METABOLISM; NERVE CELL; NONHUMAN; OXIDATION REDUCTION STATE; OXYGEN CONSUMPTION; PATHOPHYSIOLOGY; PEROXISOME; PH MEASUREMENT; PRIORITY JOURNAL; RAT; REVIEW; SPERMATOGENESIS; WOUND HEALING; BLEEDING; CELL INTERACTION; CELL LEVEL; CELL TRANSPORT; ENERGY METABOLISM; EXERCISE; HYPERGLYCEMIA; HYPOXIA; INTRACELLULAR SPACE; LACTIC ACID METABOLISM; METABOLISM; METABOLITE; SEPSIS;

ACIDOSIS, LACTIC; ANIMALS; ENERGY METABOLISM; EXERCISE; HUMANS; LACTIC ACID;

EID: 4043110513     PISSN: 00223751     EISSN: None     Source Type: Journal    
DOI: 10.1113/jphysiol.2003.058701     Document Type: Review

References (209)

1. + channels. J Physiol 544, 429-445.
2. Andrews MAW, Godt RE & Nosek TM (1996). Influence of physiological L(+)-lactate concentrations on contractility of skinned striated muscle fibers of rabbit. J Appl Physiol 80, 2060-2065.
3. Armstrong RB (1988). Muscle fiber recruitment patterns and their metabolic correlates. In Exercise, Nutrition, and Energy Metabolism, ed. Horton ES & Terjung RL, pp. 9-26. Macmillan Publishing Co., New York.
4. Attwell D (2000). Brain uptake of glutamate: food for thought. J Nutr 130, 1023S-1025S.
5. Baba N & Sharma HM (1971). Histochemistry of lactic dehydrogenase in heart and pectoralis muscles of rat. J Cell Biol 51, 621-635.
6. Bajpai M, Gupta G & Setty BS (1998). Changes in carbohydrate metabolism of testicular germ cells during meiosis in the rat. Eur J Endocrinol 138, 322-327.
7. Baldwin KM, Campbell PJ & Cooke DA (1977). Glycogen, lactate, and alanine changes in muscle fiber types during graded exercise. J Appl Physiol 43, 288-291.
8. Bangsbo J, Madsen K, Kiens B & Richter EA (1996). Effect of muscle acidity on muscle metabolism and fatigue during intense exercise in man. J Physiol 495, 587-596.
9. 3B isoforms are bona fide peroxisomal enzymes in rat liver. J Biol Chem 271, 3846-3855.
10. Bergman BC, Horning MA, Casazza GA, Wolfel EE, Butterfield GE & Brooks GA (2000). Endurance training increases gluconeogenesis during rest and exercise in men. Am J Physiol 278, E244-E251.
11. Berl S & Clarke DD (1983). The metabolic compartmentation concept. In Glutamine, Glutamate and GABA in the Central Nervous System, ed. Hertz L, Kvamme E, McGeer EG & Schousboe A, pp. 205-217. Liss, New York.
12. Bignami A (1991). Glial cells in the central nervous system. In Discussions in Neuroscience, vol. VIII, no. 1, ed. Magistretti PG, pp. 1-45. Elsevier, Amsterdam.
13. Bittar PG, Charnay Y, Pellerin L, Bouras C & Magistretti PJ (1996). Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. J Cereb Blood Flow Metab 16, 1079-1089.
14. Bonen A (2001). The expression of lactate transporters (MCT1 and MCT4) in heart and muscle. Eur J Appl Physiol 86, 6-11.
15. Bouvier M, Szatkowski M, Amaro A & Attwell D (1992). The glial cell glutamate uptake carrier countertransports pH-changing anions. Nature 360, 471-474.
16. Bouzier-Sore A-K, Merle M, Magistretti PJ & Pellerin L (2002). Feeding active neurons: (re)emergence of a nursing role for astrocytes. J Physiol Paris 96, 273-282.
17. Bouzier-Sore A-K, Voisin P, Canioni P, Magistretti PJ & Pellerin L (2003). Lactate is a preferential oxidative energy substrate over glucose for neurons in culture. J Cereb Blood Flow Metab 23, 1298-1306.
18. Brandt RB, Laux JE, Spainhour SE & Kline ES (1987). Lactate dehydrogenase in rat mitochondria. Arch Biochem Biophys 259, 412-422.
19. Bröer S, Rahman B, Pellegri G, Pellerin L, Martin J-L, Verleysdonk S, Hamprecht B & Magistretti PJ (1997). Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT1) expressing Xenopus laevis oocytes: expression of two different monocarboxylate transporters in astroglial cells and neurons. J Biol Chem 272, 30096-30102.
20. Bröer S, Schneider H-P, Bröer A, Rahman B, Hamprecht B & Deitmer JW (1998). Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochem J 333, 167-174.
21. Brooks GA (1985a). Lactate: glycolytic product and oxidative substrate during sustained exercise in mammals - the 'lactate shuttle.' In Comparative Physiology and Biochemistry: Current Topics and Trends, vol. A, Respiration-Metabolism-Circulation, ed. Gilles R, pp. 208-218. Springer, Berlin.
22. Brooks GA (1985b). Anaerobic threshold: review of the concept and directions for future research. Med Sci Sports Exerc 17, 22-31.
23. Brooks GA (1998). Mammalian fuel utilization during sustained exercise. Comp Biochem Physiol B Biochem Mol Biol 120, 89-107.
24. Brooks GA (2000). Intra- and extra-cellular lactate shuttles. Med Sci Sports Exerc 32, 790-799.
25. Brooks GA (2002a). Lactate shuttle - between but not within cells? J Physiol 541, 333.
26. Brooks GA (2002b). Lactate shuttles in nature. Biochem Soc Trans 30, 258-264.
27. Brooks GA, Brown MA, Butz CE, Sicurello JP & Dubouchaud H (1999a). Cardiac and skeletal muscle mitochondria have a monocarboxylate transporter MCT1. J Appl Physiol 87, 1713-1718.
28. Brooks GA, Dubouchaud H, Brown M, Sicurello IP & Butz CE (1999b). Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle. Proc Natl Acad Sci U S A 96, 1129-1134.
29. Brooks GA & Gladden LB (2003). The metabolic systems: anaerobic metabolism (glycolytic and phosphagen). In Exercise Physiology. People and Ideas, ed. Tipton CM, chap. 8, pp. 322-360. Oxford University Press, New York.
30. Brown AM, Wender R & Ransom BR (2001). Metabolic substrates other than glucose support axon function in central white matter. J Neurosci Res 66, 839-843.
31. +-ATPase and raises blood lactate under aerobic conditions in humans. Am J Physiol 284, H1028-H1034.
32. Bushong EA, Martone ME, Jones YZ & Ellisman MH (2002). Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci 22, 183-192.
33. Calvin J & Tubbs PK (1978). Mitochondrial transport processes and oxidation of NADH by hypotonically-treated boar spermatozoa. Eur J Biochem 89, 315-320.
34. Carpenter FG (1959). Substrates supporting activity in immature nerve fibers. Am J Physiol 197, 813-816.
35. Chatham JC, Des Rosiers C & Forder JR (2001). Evidence of separate pathways for lactate uptake and release by the perfused rat heart. Am J Physiol 281, E794-E802.
36. Chatham JC, Gao Z-P & Forder JR (1999). Impact of 1 wk of diabetes on the regulation of myocardial carbohydrate and fatty acid oxidation. Am J Physiol 277, E342-E351.
37. Chih C-P, Lipton P & Roberts EL Jr (2001). Do active cerebral neurons really use lactate rather than glucose? Trends Neurosci 24, 573-578.
38. 2 subunit and the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex. Cereb Cortex 12, 515-525.
39. + pump regulation and skeletal muscle contractility. Physiol Rev 83, 1269-1324.
40. 2 in a working red muscle in situ. J Appl Physiol 61, 402-408.
41. 2. J Appl Physiol 68, 833-842.
42. Constant JS, Feng JJ, Zabel DD, Yuan H, Suh DY, Scheuenstuhl H, Hunt TK & Hussain MZ (2000). Lactate elicits vascular endothelial growth factor from macrophages: a possible alternative to hypoxia. Wound Repair Regen 8, 353-360.
43. Courtens JL & Plöen L (1999). Improvement of spermatogenesis in adult cryptorchid rat testis by intratesticular infusion of lactate. Biol Reprod 61, 154-161.
44. Dawson AG (1979). Oxidation of cytosolic NADH formed during aerobic metabolism in mammalian cells. Trends Biochem Sci 4, 171-176.
45. Debernardi R, Pierre K, Lengacher S, Magistretti PJ & Pellerin L (2003). Cell-specific expression pattern of monocarboxylate transporters in astrocytes and neurons observed in different mouse brain cortical cell cultures. J Neurosci Res 73, 141-155.
46. Deuticke B, Beyer E & Forst B (1982). Discrimination of three parallel pathways of lactate transport in the human erythrocyte membrane by inhibitors and kinetic properties. Biochim Biophys Acta 684, 96-110.
47. Dienel GA & Hertz L (2001). Glucose and lactate metabolism during brain activation. J Neurosci Res 66, 824-838.
48. Drummond GI, Harwood JP & Powell CA (1969). Studies on the activation of phosphorylase in skeletal muscle by contraction and by epinephrine. J Biol Chem 244, 4235-4240.
49. Dubouchaud H, Butterfield GE, Wolfel EE, Bergman BC & Brooks GA (2000). Endurance training, expression, and physiology of LDH, MCT1, and MCT4 in human skeletal muscle. Am J Physiol 278, E571-E579.
50. Entman ML, Keslensky SS, Chu A & Van Winkle WB (1980). The sarcoplasmic reticulum-glycogenolytic complex in mammalian fast twitch skeletal muscle. J Biol Chem 255, 6245-6252.
51. 3H]ryanodine binding. J Appl Physiol 78, 1665-1672.
52. Fitts RH (2003). Mechanisms of muscular fatigue. In Principles of Exercise Biochemistry, 3rd edn, ed. Poortmans JR, pp. 279-300. Karger, Basel.
53. Fletcher WM & Hopkins FG (1907). Lactic acid in amphibian muscle. J Physiol 35, 247-309.
54. Gallina FG, de Burgos NMG, Burgos C, Coronel CE & Blanco A (1994). The lactate/pyruvate shuttle in spermatozoa: operation in vitro. Arch Biochem Biophys 308, 515-519.
55. Garcia CK, Brown MS, Pathak RK & Goldstein JL (1995). cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1. J Biol Chem 270, 1843-1849.
56. Garcia CK, Goldstein JL, Pathak RK, Anderson RG & Brown MS (1994). Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: Implications for the Cori cycle. Cell 76, 865-873.
57. Ghani QP, Wagner S & Hussain MZ (2003). Role of ADP-ribosylation in wound repair. The contributions of Thomas K. Hunt, MD. Wound Repair Regen 11, 439-444.
58. Gibson DR, Angeles AP & Hunt TK (1997). Increased oxygen tension on wound metabolism and collagen synthesis. Surg Forum 48, 696-699.
59. Gjedde A & Marrett S (2001). Glycolysis in neurons, not astrocytes, delays oxidative metabolism of human visual cortex during sustained checkerboard stimulation in vivo. J Cereb Blood Flow Metab 21, 1384-1392.
60. Gladden LB (1991). Net lactate uptake during progressive steady-level contractions in canine skeletal muscle. J Appl Physiol 71, 514-520.
61. Gladden LB (1996). Lactate transport and exchange during exercise. In Handbook of Physiology, section 12, Exercise: Regulation and Integration of Multiple Systems, ed. Rowell LB & Shepherd JT, pp. 614-648. Oxford University Press, New York.
62. Gladden LB (2000). Muscle as a consumer of lactate. Med Sci Sports Exerc 32, 764-771.
63. Gladden LB (2001). Lactic acid: new roles in a new millennium. Proc Natl Acad Sci U S A 98, 395-397.
64. Gladden LB (2003). Lactate metabolism during exercise. In Principles of Exercise Biochemistry, 3rd edn, ed. Poortmans JR, pp. 152-196. Karger, Basel.
65. Gladden LB, Crawford RE & Webster MJ (1994). Effect of lactate concentration and metabolic rate on net lactate uptake by canine skeletal muscle. Am J Physiol 266, R1095-R1101.
66. Gramsbergen JB, Leegsma-Vogt G, Venema K, Noraberf J & Korf J (2003). Quantitative on-line monitoring of hippocampus glucose and lactate metabolism in organotypic cultures using biosensor technology, J Neurochem 85, 399-408.
67. Green H & Goldberg B (1964). Collagen and cell protein synthesis by established mammalian fibroblast line. Nature 204, 347-349.
68. Grootegoed JA, Jansen R & van der Molen HJ (1984). The role of glucose, pyruvate and lactate in ATP production by rat spermatocytes and spermatids. Biochim Biophys Acta 767, 248-256.
69. Grootegoed JA, Oonk RB, Jansen R & van der Molen HJ (1986). Metabolism of radiolabelled energy-yielding substrates by rat Sertoli cells. J Reprod Fertil 77, 109-118.
70. Halangk W, Bohnensack R, Frank K & Kunz W (1985). Effect of various substrates on mitochondrial and cellular energy state of intact spermatozoa. Biomed Biochim Acta 44, 411-420.
71. Halestrap AP & Price NT (1999). The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 343, 281-299.
72. Hamann JJ, Kelley KM & Gladden LB (2001). Effect of epinephrine on net lactate uptake by contracting skeletal muscle. J Appl Physiol 91, 2635-2641.
73. Hassel B & Brathe A (2000). Cerebral metabolism of lactate in vivo: evidence for a neuronal pyruvate carboxylation. J Cereb Blood Flow Metab 20, 327-336.
74. Hayashi H & Takahata S (1991). Role of peroxisomal fatty acyl-CoA beta-oxidation in phospholipids biosynthesis. Arch Biochem Biophys 284, 326-331.
75. Hermansen L (1981). Effect of metabolic changes on force generation in skeletal muscle during maximal exercise. In CIBA Foundation Symposium 82. Human Muscle Fatigue: Physiological Mechanisms, ed. Porter R & Whelan J, pp. 75-88. Pitman Medical, London.
76. Hildyard JCW & Halestrap AP (2003). Identification of the mitochondrial pyruvate carrier in Saccharomyces cerevisiae. Biochem J 374, 607-611.
77. Hill AV (1932). The revolution in muscle physiology. Physiol Rev 12, 56-67.
78. Hill AV, Long CNH & Lupton H (1924). Muscular exercise, lactic acid, and the supply and utilization of oxygen. Part VI. The oxygen debt at the end of exercise. Proc R Soc Lond B Biol Sci 97, 127-137.
79. Hochachka PW (1999). The metabolic implications of intracellular circulation. Proc Natl Acad Sci U S A 96, 12233-12239.
80. Hogan MC, Gladden LB, Kurdak SS & Poole DC (1995). Increased [lactate] in working dog muscle reduces tension development independent of pH. Med Sci Sports Exerc 27, 371-377.
81. Hosoya K, Kondo T, Tomi M, Takanaga H, Ohtsuki S & Terasaki T (2001). MCT1-mediated transport of L-lactic acid at the inner blood-retinal barrier: a possible route for delivery of monocarboxylic acid drugs to the retina. Pharm Res 18, 1669-1676.
82. Hunt TK, Conolly WB, Aronson SB & Goldstein P (1978). Anaerobic metabolism and wound healing: an hypothesis for the initiation and cessation of collagen synthesis in wounds. Am J Surg 135, 328-332.
83. Ide K & Secher NH (2000). Cerebral blood flow and metabolism during exercise. Prog Neurobiol 61, 397-414.
84. Inskeep PB & Hammerstedt RH (1985). Endogenous metabolism by sperm in response to altered cellular ATP requirements. J Cell Physiol 123, 180-190.
85. Jackson VN, Price NT & Halestrap AP (1995). cDNA cloning of MCT1, a monocarboxylate transporter from rat skeletal muscle. Biochim Biophys Acta 1238, 193-196.
86. James JH, Fang C-H, Schrantz SJ, Hasselgren P-O, Paul RJ & Fischer JE (1996). Linkage of aerobic glycolysis to sodium-potassium transport in rat skeletal muscle. J Clin Invest 98, 2388-2397.
87. James JH, Luchette FA, McCarter FD & Fischer JE (1999a). Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 354, 505-508.
88. +-ATPase activity in skeletal muscle by epinephrine or amylin. Am J Physiol 277, E176-E186.
89. Johnson RE, Edwards HT, Dill DB & Wilson JW (1945). Blood as a physicochemical system: the distribution of lactate. J Biol Chem 157, 461-473.
90. Johnson RL Jr, Heigenhauser GJF, Hsia CCW, Jones NL & Wagner PD (1996). Determinants of gas exchange and acid-base balance during exercise. In Handbook of Physiology, section 12, Exercise: Regulation and Integration of Multiple Systems, ed. Rowell LB & Shepherd JT, pp. 515-584. Oxford University Press, New York.
91. Jones AR (1997). Metabolism of lactate by mature boar spermatozoa. Reprod Fertil Dev 9, 227-232.
92. Jorfeldt L (1970). Metabolism of L(+)-lactate in human skeletal muscle during exercise. Acta Physiol Scand 338 (suppl.), 1-67.
93. + transport in human skeletal muscle. Eur J Appl Physiol 86, 12-16.
94. Juel C, Bangsbo J, Graham T & Saltin B (1990). Lactate and potassium fluxes from human skeletal muscle during and after intense, dynamic, knee extensor exercise. Acta Physiol Scand 140, 147-159.
95. Juel C & Halestrap AP (1999). Lactate transport in skeletal muscle - role and regulation of the monocarboxylate transporter. J Physiol 517, 633-642.
96. Karlsson J (1971). Lactate and phosphagen concentrations in working muscle of man with special reference to oxygen deficit at the onset of work. Acta Physiol Scand Suppl 358, 1-72.
97. Keilin D (1966). The History of Cell Respiration and Cytochrome, p. 68. Cambridge University Press, Cambridge.
98. Kelley KM, Hamann JJ, Navarre C & Gladden LB (2002). Lactate metabolism in resting and contracting canine skeletal muscle with elevated lactate concentration. J Appl Physiol 93, 865-872.
99. Keyhani E & Storey BT (1973). Energy conservation capacity and morphological integrity of miotchondria in hypotonically treated rabbit epididymal spermatozoa. Biochim Biophys Acta 305, 557-569.
100. Kimelberg HK, Jalonen T & Walz W (1993). Regulation of brain microenvironment: transmitters and ions. In Astrocytes: Pharmacology and Function, ed. Murphy S, pp. 193-228. Academic Press, San Diego, CA.
101. Kline ES, Brandt RB, Laux JE, Spainhour SE, Higgins ES, Rogers KS, Tinsley SB & Waters MG (1986). Localization of L-lactate dehydrogenase in mitochondria. Arch Biochem Biophys 246, 673-680.
102. Kowalchuk JM, Heigenhauser GJF, Lindinger MI, Sutton JR & Jones NL (1988). Factors influencing hydrogen ion concentration in muscle after intense exercise. J Appl Physiol 65, 2080-2089.
103. Krützfeldt A, Spahr R, Mertens S, Siegmund B & Piper HM (1990). Metabolism of exogenous substrates by coronary endothelial cells in culture. J Mol Cell Cardiol 22, 1393-1404.
104. Kuan J & Saier MH (1993). The mitochondrial carrier family of transport proteins: structural, functional and evolutionary relationships. Crit Rev Biochem Mol Biol 28, 209-233.
105. Kuhn TS (1970). The Structure of Scientific Revolutions, p. 10. University of Chicago Press, Chicago.
106. Lai JC, Behar KL, Liang BB & Hertz L (1999). Hexokinase in astrocytes: kinetic and regulatory properties. Metab Brain Dis 14, 125-133.
107. Larrabee MG (1995). Lactate metabolism and its effect on glucose metabolism in an excised neural tissue. J Neurochem 64, 1734-1741.
108. Lazarow PB & de Duve C (1976). A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug. Proc Natl Acad Sci U S A 73, 2043-2046.
109. Leegsma-Vogt G, Venema K & Korf J (2003). Evidence for a lactate pool in the rat brain that is not used as an energy supply under normoglycemic conditions. J Cereb Blood Flow Metab 23, 933-941.
110. Lindinger MI (2003). Exercise: a paradigm for multi-system control of acid-base state. J Physiol 550, 334.
111. Lindinger MI, Heigenhauser GJF, McKelvie RS & Jones NL (1992). Blood ion regulation during repeated maximal exercise and recovery in humans. Am J Physiol 262, R126-R136.
112. - distribution in humans during and after high-intensity exercise: role in muscle fatigue attenuation? J Appl Physiol 78, 765-777.
113. Lloyd S, Brocks C & Chatham JC (2003). Differential modulation of glucose, lactate, and pyruvate oxidation by insulin and dichloroacetate in rat heart. Am J Physiol 285, H163-H172.
114. Loaiza A, Porras OH & Barros LF (2003). Glutamate triggers rapid glucose transport stimulation in astrocytes as evidenced by real-time confocal microscopy. J Neurosci 23, 7337-7342.
115. Luchette FA, Jenkins WA, Friend LA, Su C, Fischer JE & James JH (2002). Hypoxia is not the sole cause of lactate production during shock. J Trauma 52, 415-419.
116. Mac M & Nalecz KA (2003). Expression of monocarboxylic acid transporters (MCT) in brain cells. Implications for branched chain alpha-ketoacids transport in neurons. Neurochem Int 43, 305-309.
117. +-ATPase activity during hemorrhage. J Surg Res 99, 235-244.
118. McClelland GB, Khanna S, González GF, Butz CE & Brooks GA (2003). Peroxisomal membrane monocarboxylate transporters: evidence for a redox shuttle system? Biochem Biophys Res Commun 304, 130-135.
119. McGroarty E, Hsieh B, Wied DM, Gee R & Tolbert NE (1974). Alpha hydroxyl acid oxidation by peroxisomes. Arch Biochem Biophys 161, 194-210.
120. McIlwain H (1956). Electrical influences and speed of chemical changes. Physiol Rev 36, 355-375.
121. Magistretti PJ & Pellerin L (1999). Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond B Biol Sci 354, 1155-1163.
122. Magistretti PJ, Pellerin L, Rothman DL & Shulman RG (1999). Energy on demand. Science 283, 496-497.
123. Mangia S, Garreffa G, Bianciardi M, Giove F, Di Salle F & Maraviglia B (2003a). The aerobic brain: lactate decrease at the onset of neural activity. Neuroscience 118, 7-10.
124. Mangia S, Giove F, Bianciardi M, Di Salle F, Garreffa G & Maraviglia B (2003b). Issues concerning the construction of a metabolic model for neuronal activation. J Neurosci Res 71, 463-467.
125. Margaria R, Edwards RHT & Dill DB (1933). The possible mechanisms of contracting and paying the oxygen debt and the role of lactic acid in muscular contraction. Am J Physiol 106, 689-715.
126. Mathews CK, van Holde KE & Ahern KG (2000). Biochemistry, p. 648. Addison-Wesley Longman, Inc, New York.
127. 13C]lactate in humans during rest and exercise. J Appl Physiol 60, 232-241.
128. Meeks JP & Mennerick S (2003). Feeding hungry neurons: astrocytes deliver food for thought. Neuron 37, 187-189.
129. Meyerhof O (1920). Die Energieumwandlungen im Muskel. I. Über die Beziehungen der Milchsaure zur Warmebildung and Arbeitsleistung des Muskels in der Anaerobiose. Pflugers Arch Ges Physiol Mensch Tiere 182, 232-283.
130. Milkowski AL & Lardy HA (1977). Factors affecting the redox state of bovine epididymal spermatozoa. Arch Biochem Biophys 181, 270-277.
131. Miller BF, Fattor JA, Jacobs KA, Horning MA, Navazio F, Lindinger MI & Brooks GA (2002a). Lactate and glucose interactions during rest and exercise in men: effect of exogenous lactate infusion. J Physiol 544, 963-975.
132. Miller BF, Fattor JA, Jacobs KA, Horning MA, Suh S-H, Navazio F & Brooks GA (2002b). Metabolic and cardiorespiratory responses to 'the lactate clamp'. Am J Physiol 283, E889-E898.
133. Mizock BA & Falk JL (1992). Lactic acidosis in critical illness. Crit Care Med 20, 80-93.
134. + channels. J Mol Cell Cardiol 30, 349-356.
135. von Muralt A (1950). The development of muscle-chemistry, a lesson in neurophysiology. Biochim Biophys Acta 4, 126-129.
136. Myers RE & Yamaguchi S (1977). Nervous system effects of cardiac arrest in monkeys. Arch Neurol 34, 65-74.
137. Nakamura M, Okinaga S & Arai K (1984). Metabolism of round spermatids: evidence that lactate is preferred substrate. Am J Physiol 247, E234-E242.
138. Newsholme EA (2003). Enzymes, energy and endurance. In Principles of Exercise Biochemistry, 3rd edn, ed. Poortmans JR, pp. 1-35. Karger, Basel.
139. +-pump protects muscle excitability and contractility during exercise. Exerc Sport Sci Rev 28, 159-164.
140. Nielsen HB, Clemmesen JO, Skak C, Ott P & Secher NH (2002). Attenuated hepatosplanchnic uptake of lactate during intense exercise in humans, J Appl Physiol 92, 1677-1683.
141. Nielsen OB, de Paoli F & Overgaard K (2001). Protective effects of lactic acid on force production in rat skeletal muscle. J Physiol 536, 161-166.
142. Osmundsen H (1982). Factors which can influence beta-oxidation by peroxisomes isolated from livers of clofibrate treated rats. Some properties of peroxisomal fractions isolated in a self-generated Percoll gradient by vertical rotor centrifugation. Int J Biochem 14, 905-914.
143. Osmundsen H, Hovik R, Bartlett K & Pourfazam M (1994). Regulation of flux of acyl-CoA esters through peroxisomal β -oxidation. Biochem Soc Trans 22, 436-441.
144. Palmieri F, Bisaccia F, Capobianco L, Dolce V, Fiermonte G, Iacobazzi V, Indiveri C & Palmieri L (1996). Mitochondrial metabolite transporters. Biochim Biophys Acta 1275, 127-132.
145. Parker JC & Hoffman JF (1967). The role of membrane phosphoglycerate kinase in the control of glycolytic rate by active cation transport in human red blood cells. J General Physiol 50, 893-916.
146. Parolin ML, Chesley A, Matsos MP, Spriet LL, Jones NL & Heigenhauser GJF (1999). Regulation of skeletal muscle glycogen phosphorylase and PDH during maximal intermittent exercise. Am J Physiol 277, E890-E900.
147. 2+ uptake in smooth muscle plasma membrane vesicles by an endogenous glycolytic cascade. FASEB J 3, 2298-2301.
148. Payne RS, Tseng MT & Schurr A (2003). The glucose paradox of cerebral ischemia: evidence for corticosterone involvement. Brain Res 971, 9-17.
149. Pellerin L (2003). Lactate as a pivotal element in neuron-glia metabolic cooperation. Neurochem Int 43, 331-338.
150. Pellerin L & Magistretti PJ (1994). Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A 91, 10625-10629.
151. +-ATPase activity in astrocytes via activation of a distinct subunit highly sensitive to ouabain. J Neurochem 69, 2132-2137.
152. Pellerin L & Magistretti PJ (2003). How to balance the brain energy budget while spending glucose differently. J Physiol 546, 325.
153. Pellerin L, Pellegri G, Bittar PG, Charnay Y, Bouras C, Martin J-L, Stella N & Magistretti PJ (1998). Evidence supporting the existence of an astrocyte-neuron lactate shuttle. Dev Neurosci 20, 291-299.
154. Peters A, Palay SL & Webster H de F (1991). The Fine Structure of the Nervous System: Neurons and Their Supporting Cells. Saunders, Philadelphia.
155. Poitry-Yamate CL, Poitry S & Tsacopoulos M (1995). Lactate released by Müller glial cells is metabolized by photoreceptors from mammalian retina. J Neurosci 15, 5179-5191.
156. Popinigis J, Antosiewiez J, Crimi M, Lenaz G & Wakabayashi T (1991). Human skeletal muscle: participation of different metabolic activities in oxidation of L-lactate. Acta Biochim Pol 38, 169-175.
157. Posterino GS, Dutka TL & Lamb GD (2001). L(+)-lactate does not affect twitch and tetanic responses in mechanically skinned mammalian muscle fibres. Pflugers Arch 442, 197-203.
158. 13C NMR spectroscopy study of lactate as substrate for rat brain. Dev Neurosci 22, 429-436.
159. Rasmussen HN, Van Hall G & Rasmussen UF (2002). Lactate dehydrogenase is not a mitochondrial enzyme in human and mouse vastus lateralis muscle. J Physiol 541, 575-580.
160. 2. J Appl Physiol 85, 627-634.
161. Richter EA, Kiens B, Saltin B, Christensen NJ & Savard G (1988). Skeletal muscle glucose uptake during dynamic exercise in humans: role of muscle mass. Am J Physiol 254, E555-E561.
162. Robinson MB & Dowd LA (1997). Heterogeneity and functional properties of subtypes of sodium-dependent glutamate transporters in the mammalian central nervous system. Adv Pharmacol 37, 69-115.
163. Roef MJ, de Meer K, Kalhan SC, Straver H, Berger R & Reijngoud D-J (2003). Gluconeogenesis in humans with induced hyperlactatemia during low-intensity exercise. Am J Physiol 284, E1162-E1171.
164. Rohlmann A & Wolff JR (1996). Subcellular topography and plasticity of gap junction distribution on astrocytes. In Gap Junctions in the Nervous System, ed. Spray DC & Dermietzel R, pp. 175-192. RG Landes, Austin, TX.
165. Roth DA & Brooks GA (1990a). Lactate transport is mediated by a membrane-bound carrier in rat skeletal muscle sarcolemmal vesicles. Arch Biochem Biophys 279, 377-385.
166. Roth DA & Brooks GA (1990b). Lactate and pyruvate transport is dominated by a pH gradient-sensitive carrier in rat skeletal muscle sarcolemmal vesicles. Arch Biochem Biophys 279, 386-394.
167. Rush JWE & Spriet LL (2001). Skeletal muscle glycogen phosphorylase a kinetics: Effects of adenine nucleotides and caffeine. J Appl Physiol 91, 2071-2078.
168. Sahlin K (1992). Metabolic factors in fatigue. Sports Med 13, 99-107.
169. Sahlin K, Fernström M, Svensson M & Tonkonogi M (2002). No evidence of an intracellular lactate shuttle in rat skeletal muscle. J Physiol 541, 569-574.
170. Sahlin K, Harris RC, Nylind B & Hultman E (1976). Lactate content and pH in muscle samples obtained after dynamic exercise. Pflugers Arch 367, 143-149.
171. Salway JG (1999). Metabolism at a Glance, pp. 21 and 84-85. Blackwell Science, London.
172. +. Am J Physiol 276, H3-H8.
173. Schousboe A, Sonnewald U & Waagepetersen HS (2003). Differential roles of alanine in GABAergic and glutamatergic neurons. Neurochem Int 43, 311-315.
174. Schousboe A, Westergaard N, Waagepetersen HS, Larsson OM, Bakken IJ & Sonnewald U (1997). Trafficking between glia and neurons of TCA cycle intermediates and related metabolites. Glia 21, 99-105.
175. Schurr A (2002). Lactate, glucose and energy metabolism in the ischemic brain (Review). Int J Mol Med 10, 131-136.
176. Schurr A, Dong W-Q, Reid KH, West CA & Rigor BM (1988). Lactic acidosis and recovery of neuronal function following cerebral hypoxia in vitro. Brain Res 438, 311-314.
177. Schurr A, Payne RS, Miller JJ, Tseng MT & Rigor BM (2001). Blockade of lactate transport exacerbates delayed neuronal damage in a rat model of cerebral ischemia. Brain Res 895, 268-272.
178. Schurr A & Rigor BM (1998). Brain anaerobic lactate production: a suicide note or a survival kit.? Der Neurosci 20, 348-357.
179. Schurr A, West CA, Reid KH, Tseng MT, Reiss SJ & Rigor BM (1987). Increased glucose improves recovery of neuronal function after cerebral hypoxia in vitro. Brain Res 421, 135-139.
180. Sheikh AY, Gibson JJ, Rollins MD, Hopf HW, Hussain Z & Hunt TK (2000). Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg 135, 1293-1297.
181. Sibson NR, Dhankhar A, Mason GF, Rothman DL, Behar KL & Shulman RG (1998). Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc Natl Acad Sci U S A 95, 316-321.
182. Siesjo BK (1981). Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1, 155-185.
183. Skelton MS, Kremer DE, Smith EW & Gladden LB (1995). Lactate influx into red blood cells of athletic and nonathletic species. Am J Physiol 268, R1121-R1128.
184. Skelton MS, Kremer DE, Smith EW & Gladden LB (1998). Lactate influx into red blood cells from trained and untrained human subjects. Med Sci Sports Exerc 30, 536-542.
185. Smith D, Pernet A, Hallett WA, Bingham E, Marsden PK & Amiel SA (2003). Lactate: a preferred fuel for human brain metabolism. In Vivo J Cereb Blood Flow Metab 23, 658-664.
186. Smith EW, Skelton MS, Kremer DE, Pascoe DD & Gladden LB (1997). Lactate distribution in the blood during progressive exercise. Med Sci Sports Exerc 29, 654-660.
187. Smith EW, Skelton MS, Kremer DE, Pascoe DD & Gladden LB (1998). Lactate distribution in the blood during steady-state exercise. Med Sci Sports Exerc 30, 1424-1429.
188. Spangenburg EE, Ward CW & Williams JH (1998). Effects of lactate on force production by mouse EDL muscle: Implications for the development of fatigue. Can J Physiol Pharmacol 76, 642-648.
189. Spriet LL (1991). Phosphofructokinase activity and acidosis during short-term tetanic contractions. Can J Physiol Pharmacol 69, 298-304.
190. Spriet LL (1992). Anaerobic metabolism in human skeletal muscle during short-term, intense activity. Can J Physiol Pharmacol 70, 157-165.
191. Stainsby WN & Brooks GA (1990). Control of lactic acid metabolism in contracting muscles and during exercise. Exerc Sport Sci Rev 18, 29-63.
192. Stainsby WN & Welch HG (1966). Lactate metabolism of contracting dog skeletal muscle in situ. Am J Physiol 211, 177-183.
193. Stanley WC (1991). Myocardial lactate metabolism during exercise. Med Sci Sports Exerc 23, 920-924.
194. Stanley WC, Gertz EW, Wisneski JA, Neese RA, Morris DL & Brooks GA (1986). Lactate extraction during net lactate release in legs of humans during exercise. J Appl Physiol 60, 1116-1120.
195. Stewart PA (1981). How to Understand Acid-Base: A Quantitative Acid-Base Primer for Biology and Medicine. Elsevier, New York.
196. Storey BT & Kayne FJ (1977). Energy metabolism of spermatozoa. VI. Direct intramitochondrial lactate oxidation by rabbit sperm mitochondria. Biol Reprod 16, 549-556.
197. Sugden MC & Holness MJ (2003). Trials, tribulations and finally, a transporter: the identification of the mitochondrial pyruvate transporter. Biochem J 374, e1-e2.
198. Szczesna-Kaczmarek A (1990). L-lactate oxidation by skeletal muscle mitochondria. Int J Biochem 22, 617-620.
199. Thomas S & Fell DA (1998). A control analysis exploration of the role of ATP utilisation in glycolytic-flux control and glycolytic-metabolite-concentration regulation. Eur J Biochem 258, 956-967.
200. Trabold O, Wagner S, Wicke C, Scheuenstuhl H, Hussain MZ, Rosen N, Seremetiev A, Becker HD & Hunt TK (2003). Lactate and oxygen constitute a fundamental regulatory mechanism in wound healing. Wound Repair Regen 11, 504-509.
201. Van Hall G, Calbet JAL, Søondergaard H & Saltin B (2002). Skeletal muscle carbohydrate and lactate metabolism after 9 wk of acclimatization to 5,260 m. Am J Physiol 283, E1203-E1213.
202. Van Roermund CWT, Elgersma Y, Singh N, Wanders RJA & Tabak HF (1995). The membrane of peroxisomes in Saccharomyces cerevisiae is impermeable to NAD(H) and acetyl-CoA under in vivo conditions. EMBO J 14, 3480-3486.
203. Véga C, Poitry-Yamate CL, Jirounek P, Tsacopoulos M & Coles JA (1998). Lactate is released and taken up by isolated rabbit vagus nerve during aerobic metabolism, J Neurochem 71, 330-337.
204. Voutsinos-Porche B, Bonvento G, Tanaka K, Steiner P, Welker E, Chatton J-Y, Magistretti PJ & Pellerin L (2003). Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron 37, 275-286.
205. Waagepetersen HS, Sonnewald U, Larsson OM & Schousboe A (2000). A possible role of alanine for ammonia transfer between astrocytes and glutamatergic neurons. J Neurochem 75, 471-479.
206. Wasserman K (1984). The anaerobic threshold to evaluate exercise performance. Am Rev Respir Dis 129 (suppl.), S35-S40.
207. Westerblad H, Allen DG & Lännergren J (2002). Muscle fatigue: Lactic acid or inorganic phosphate the major cause? News Physiol Sci 17, 17-21.
208. 2+ transport. Circ Res 77, 88-97.
209. 13C] alanine in astrocytes, neurons, and cocultures: implications for glia-neuron interactions in neurotransmitter metabolism. Glia 32, 286-303.