Lactate metabolism: a new paradigm for the third millennium

Journal of Physiology - Tập 558 Số 1 - Trang 5-30 - 2004
L. Bruce Gladden1
1Department of Health and Human Performance, 2050 Memorial Coliseum, Auburn University, Auburn, AL 36849-5323, USA

Tóm tắt

For much of the 20th century, lactate was largely considered a dead‐end waste product of glycolysis due to hypoxia, the primary cause of the O2 debt following exercise, a major cause of muscle fatigue, and a key factor in acidosis‐induced tissue damage. Since the 1970s, a ‘lactate revolution’ has occurred. At present, we are in the midst of a lactate shuttle era; the lactate paradigm has shifted. It now appears that increased lactate production and concentration as a result of anoxia or dysoxia are often the exception rather than the rule. Lactic acidosis is being re‐evaluated as a factor in muscle fatigue. Lactate is an important intermediate in the process of wound repair and regeneration. The origin of elevated [lactate] in injury and sepsis is being re‐investigated. There is essentially unanimous experimental support for a cell‐to‐cell lactate shuttle, along with mounting evidence for astrocyte–neuron, lactate–alanine, peroxisomal and spermatogenic lactate shuttles. The bulk of the evidence suggests that lactate is an important intermediary in numerous metabolic processes, a particularly mobile fuel for aerobic metabolism, and perhaps a mediator of redox state among various compartments both within and between cells. Lactate can no longer be considered the usual suspect for metabolic ‘crimes’, but is instead a central player in cellular, regional and whole body metabolism. Overall, the cell‐to‐cell lactate shuttle has expanded far beyond its initial conception as an explanation for lactate metabolism during muscle contractions and exercise to now subsume all of the other shuttles as a grand description of the role(s) of lactate in numerous metabolic processes and pathways.

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Tài liệu tham khảo

10.1113/jphysiol.2002.022434

Andrews MAW, 1996, Influence of physiological L(+)‐lactate concentrations on contractility of skinned striated muscle fibers of rabbit, J Appl Physiol, 80, 2060, 10.1152/jappl.1996.80.6.2060

Armstrong RB, 1988, Exercise, Nutrition, and Energy Metabolism, 9

10.1093/jn/130.4.1023S

10.1083/jcb.51.3.621

10.1530/eje.0.1380322

Baldwin KM, 1977, Glycogen, lactate, and alanine changes in muscle fiber types during graded exercise, J Appl Physiol, 43, 288, 10.1152/jappl.1977.43.2.288

10.1113/jphysiol.1996.sp021618

10.1074/jbc.271.7.3846

10.1152/ajpendo.2000.278.2.E244

Berl S, 1983, Glutamine, Glutamate and GABA in the Central Nervous System, 205

Bignami A, 1991, Discussions in Neuroscience, vol. VIII, no. 1, 1

10.1097/00004647-199611000-00001

10.1007/s004210100516

10.1038/360471a0

10.1016/S0928-4257(02)00016-5

10.1097/01.WCB.0000091761.61714.25

10.1016/0003-9861(87)90507-8

10.1074/jbc.272.48.30096

10.1042/bj3330167

10.1007/978-3-642-70610-3_15

10.1249/00005768-198502000-00005

10.1016/S0305-0491(98)00025-X

10.1097/00005768-200004000-00011

10.1113/jphysiol.2002.023705

10.1042/bst0300258

10.1152/jappl.1999.87.5.1713

10.1073/pnas.96.3.1129

10.1007/978-1-4614-7543-9_8

10.1002/jnr.10081

10.1152/ajpheart.00639.2002

10.1523/JNEUROSCI.22-01-00183.2002

10.1111/j.1432-1033.1978.tb20929.x

Carpenter FG, 1959, Substrates supporting activity in immature nerve fibers, Am J Physiol, 197, 813, 10.1152/ajplegacy.1959.197.4.813

10.1152/ajpendo.2001.281.4.E794

10.1152/ajpendo.1999.277.2.E342

10.1016/S0166-2236(00)01920-2

10.1093/cercor/12.5.515

10.1152/physrev.00011.2003

10.1152/jappl.1986.61.2.402

10.1152/jappl.1990.68.3.833

10.1111/j.1524-475X.2000.00353.x

10.1095/biolreprod61.1.154

10.1016/0968-0004(79)90417-1

10.1002/jnr.10660

10.1016/0005-2736(82)90053-0

10.1002/jnr.10079

Drummond GI, 1969, Studies on the activation of phosphorylase in skeletal muscle by contraction and by epinephrine, J Biol Chem, 244, 4235, 10.1016/S0021-9258(17)36406-2

10.1152/ajpendo.2000.278.4.E571

Entman ML, 1980, The sarcoplasmic reticulum‐glycogenolytic complex in mammalian fast twitch skeletal muscle, J Biol Chem, 255, 6245, 10.1016/S0021-9258(18)43730-1

10.1152/jappl.1995.78.5.1665

10.1159/000074371

10.1113/jphysiol.1907.sp001194

10.1006/abbi.1994.1072

10.1074/jbc.270.4.1843

10.1016/0092-8674(94)90361-1

10.1046/j.1524-475X.2003.11608.x

Gibson DR, 1997, Increased oxygen tension on wound metabolism and collagen synthesis, Surg Forum, 48, 696

10.1097/00004647-200112000-00002

10.1152/jappl.1991.71.2.514

Gladden LB, 1996, Handbook of Physiology, section 12, Exercise: Regulation and Integration of Multiple Systems, 614

10.1097/00005768-200004000-00008

10.1073/pnas.98.2.395

10.1159/000074368

10.1152/ajpregu.1994.266.4.R1095

10.1046/j.1471-4159.2003.01673.x

10.1038/204347a0

10.1016/0005-2728(84)90194-4

10.1530/jrf.0.0770109

Halangk W, 1985, Effect of various substrates on mitochondrial and cellular energy state of intact spermatozoa, Biomed Biochim Acta, 44, 411

10.1042/bj3430281

10.1152/jappl.2001.91.6.2635

10.1097/00004647-200002000-00014

10.1016/0003-9861(91)90303-Z

Hermansen L, 1981, CIBA Foundation Symposium 82. Human Muscle Fatigue: Physiological Mechanisms, 75, 10.1002/9780470715420.ch5

10.1042/bj20030995

10.1152/physrev.1932.12.1.56

Hill AV, 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

10.1073/pnas.96.22.12233

10.1249/00005768-199503000-00013

10.1023/A:1013310210710

10.1016/0002-9610(78)90061-2

10.1016/S0301-0082(99)00057-X

10.1002/jcp.1041230205

10.1016/0005-2736(95)00160-5

10.1172/JCI119052

10.1016/S0140-6736(98)91132-1

10.1152/ajpendo.1999.277.1.E176

Johnson RE, 1945, Blood as a physicochemical system: the distribution of lactate, J Biol Chem, 157, 461, 10.1016/S0021-9258(18)51082-6

Johnson RL, 1996, Handbook of Physiology, section 12, Exercise: Regulation and Integration of Multiple Systems, 515

10.1071/R96102

Jorfeldt L, 1970, Metabolism of L(+)‐lactate in human skeletal muscle during exercise, Acta Physiol Scand, 338, 1

10.1007/s004210100517

10.1111/j.1748-1716.1990.tb08986.x

10.1111/j.1469-7793.1999.0633s.x

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

Keilin D, 1966, The History of Cell Respiration and Cytochrome, 68

10.1152/japplphysiol.01119.2001

10.1016/0005-2728(73)90075-3

10.1016/B978-0-12-511370-0.50013-8

10.1016/0003-9861(86)90323-1

10.1152/jappl.1988.65.5.2080

10.1016/0022-2828(90)90984-A

10.3109/10409239309086795

Kuhn TS, 1970, The Structure of Scientific Revolutions, 10

10.1023/A:1020761831295

10.1046/j.1471-4159.1995.64041734.x

10.1073/pnas.73.6.2043

10.1097/01.WCB.0000080650.64357.8F

10.1113/jphysiol.2003.042812

10.1152/ajpregu.1992.262.1.R126

10.1152/jappl.1995.78.3.765

10.1152/ajpheart.01117.2002

10.1523/JNEUROSCI.23-19-07337.2003

10.1097/00005373-200203000-00001

10.1016/S0197-0186(03)00016-0

10.1006/jsre.2001.6175

10.1016/S0006-291X(03)00550-3

10.1016/0003-9861(74)90251-3

10.1152/physrev.1956.36.3.355

10.1098/rstb.1999.0471

10.1126/science.283.5401.496

10.1016/S0306-4522(02)00792-3

10.1002/jnr.10531

Margaria R, 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, 10.1152/ajplegacy.1933.106.3.689

Mathews CK, 2000, Biochemistry, 648

10.1152/jappl.1986.60.1.232

10.1016/S0896-6273(03)00027-8

10.1007/BF01723747

10.1016/0003-9861(77)90505-7

10.1113/jphysiol.2002.027128

10.1152/ajpendo.00266.2002

10.1097/00003246-199201000-00020

10.1006/jmcc.1997.0598

10.1016/0006-3002(50)90015-1

10.1001/archneur.1977.00500140019003

10.1152/ajpendo.1984.247.2.E234

10.1159/000074361

Nielsen OB, 2000, The Na+/K+‐pump protects muscle excitability and contractility during exercise, Exerc Sport Sci Rev, 28, 159

10.1152/japplphysiol.00028.2001

10.1111/j.1469-7793.2001.t01-1-00161.x

10.1016/0020-711X(82)90074-X

10.1042/bst0220436

10.1016/0005-2728(96)00062-X

10.1085/jgp.50.4.893

10.1152/ajpendo.1999.277.5.E890

10.1096/fasebj.3.11.2528493

10.1016/S0006-8993(03)02276-5

10.1016/S0197-0186(03)00020-2

10.1073/pnas.91.22.10625

10.1046/j.1471-4159.1997.69052132.x

10.1113/jphysiol.2002.035105

10.1159/000017324

Peters A, 1991, The Fine Structure of the Nervous System: Neurons and Their Supporting Cells

10.1523/JNEUROSCI.15-07-05179.1995

Popinigis J, 1991, Human skeletal muscle: participation of different metabolic activities in oxidation of L‐lactate, Acta Biochim Pol, 38, 169

10.1007/s004240100528

10.1159/000017472

10.1113/jphysiol.2002.019216

10.1152/jappl.1998.85.2.627

10.1152/ajpendo.1988.254.5.E555

10.1016/S1054-3589(08)60948-5

10.1152/ajpendo.00425.2002

10.1007/978-3-662-21935-5_10

10.1016/0003-9861(90)90505-S

10.1016/0003-9861(90)90506-T

10.1152/jappl.2001.91.5.2071

10.2165/00007256-199213020-00005

10.1113/jphysiol.2002.016683

10.1007/BF00585150

Salway JG, 1999, Metabolism at a Glance, 21

10.1152/ajpheart.1999.276.1.H3

10.1016/S0197-0186(03)00017-2

10.1002/(SICI)1098-1136(199709)21:1<99::AID-GLIA11>3.0.CO;2-W

Schurr A, 2002, Lactate, glucose and energy metabolism in the ischemic brain (Review), Int J Mol Med, 10, 131

10.1016/0006-8993(88)91354-6

10.1016/S0006-8993(01)02082-0

10.1159/000017330

10.1016/0006-8993(87)91283-2

10.1001/archsurg.135.11.1293

10.1073/pnas.95.1.316

10.1038/jcbfm.1981.18

Skelton MS, 1995, Lactate influx into red blood cells of athletic and nonathletic species, Am J Physiol, 268, R1121

10.1097/00005768-199804000-00011

10.1097/01.WCB.0000063991.19746.11

10.1097/00005768-199705000-00011

10.1249/00005768-199809000-00012

Spangenburg EE, 1998, Effects of lactate on force production by mouse EDL muscle: Implications for the development of fatigue, Can J Physiol Pharmacol, 76, 642, 10.1139/y98-061

10.1139/y91-046

10.1139/y92-023

10.1249/00003677-199001000-00005

10.1152/ajplegacy.1966.211.1.177

10.1249/00005768-199108000-00006

10.1152/jappl.1986.60.4.1116

Stewart PA, 1981, How to Understand Acid‐Base: A Quantitative Acid‐Base Primer for Biology and Medicine

Storey BT, 1977, Energy metabolism of spermatozoa. VI. Direct intramitochondrial lactate oxidation by rabbit sperm mitochondria, Biol Reprod, 16, 549

10.1042/bj20031105

10.1016/0020-711X(90)90038-5

10.1046/j.1432-1327.1998.2580956.x

10.1046/j.1524-475X.2003.11621.x

10.1152/ajpendo.00134.2001

10.1002/j.1460-2075.1995.tb07354.x

10.1046/j.1471-4159.1998.71010330.x

10.1016/S0896-6273(02)01170-4

10.1046/j.1471-4159.2000.0750471.x

10.1164/arrd.1984.129.2P2.S35

Westerblad H, 2002, Muscle fatigue: Lactic acid or inorganic phosphate the major cause, News Physiol Sci, 17, 17

10.1161/01.RES.77.1.88

10.1002/1098-1136(200012)32:3<286::AID-GLIA80>3.0.CO;2-P