Comprehensive Physiology Wiley Online Library

Lactate Transport and Exchange During Exercise

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Why Does [La] Increase During Exercise?
1.1 Muscle Hypoxia: The Traditional Hypothesis
1.2 Evidence Against Muscle Hypoxia
1.3 Multiple Factors
1.4 Criticism of Evidence Against O2‐limitation
1.5 Near‐Equilibrium Steady State: A Unifying Hypothesis?
1.6 Summary
2 The Lactate Shuttle
3 Carrier‐Mediated Lactate Transport
3.1 Lactate Transport in Sarcolemmal Vesicles
3.2 Lactate Transport in Isolated Cells
3.3 Reconstitution of the Lactate Carrier
3.4 Lactate Transport In Situ
3.5 Summary
4 Muscle as a Consumer of Lactate: Regulating Factors
4.1 Lactate Concentration
4.2 Metabolic Rate
4.3 Blood Flow
4.4 Hydrogen Ion Concentration
4.5 Muscle Fiber Type
4.6 Exercise Training
4.7 Summary
5 Blood Transport of Lactate
5.1 Lactate Distribution between Plasma and RBCs
5.2 Comparative Aspects of Lactate Transport in RBCs
6 Altitude
6.1 The Lactate Paradox
6.2 Explanations for the Lactate Paradox
6.3 Summary
Figure 1. Figure 1.

Relationship between oxygen consumption and partial pressure of oxygen in mitochondria isolated from rat heart. Note that oxygen consumption is maximal down to very low partial pressures. Other techniques have shown that mitochondrial oxygen consumption is independent of oxygen partial pressure down to ∼0.5 mm Hg. See text for details.

Redrawn with permission from Rumsey, W. L., C. Schlosser, E. M. Nuutinen, M. Robiolio, and D. F. Wilson. Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat. J. Biol. Chem. 265: 15392–15399, 1990
Figure 2. Figure 2.

Schematic illustration of relationship between lactate rate of appearance, lactate rate of disappearance, and resulting blood [La] during progressive, incremental exercise.

Redrawn with permission from Brooks, G. A. Anaerobic threshold: review of the concept and directions for future research. Med. Sci. Sports Exerc. 17: 22–31, 1985
Figure 3. Figure 3.

Predicted dependence of mitochondrial oxygen consumption on partial pressure of oxygen at high‐ and low‐energy states with constant [NAD+]/[NADH] of 1.0. Note that oxygen independence is preserved to low partial pressures when energy state is low.

Based on mathematical models of, and redrawn with permission from, Wilson, D. F., C. S. Owen, and M. Erecinska. Quantitative dependence of mitochondrial oxidative phosphorylation on oxygen concentration: a mathematical model. Arch. Biochem. Biophys. 195: 494–504, 1979
Figure 4. Figure 4.

Predicted dependence of mitochondrial oxygen consumption on partial pressure of oxygen at high and low [NAD+]/[NADH] with constant [ATP]/[ADP][Pi] of 500 · M−1. Note that oxygen independence is preserved to low partial pressures when [NAD+]/[NADH] is low.

Based on mathematical models of, and redrawn with permission from, Wilson, D. F., C. S. Owen, and M. Erecinska. Quantitative dependence of mitochondrial oxidative phosphorylation on oxygen concentration: a mathematical model. Arch. Biochem. Biophys. 195: 494–504, 1979
Figure 5. Figure 5.

Relationship between energy state and oxygen uptake in dog gastrocnemius muscle in situ at rest and two stimulation rates for normoxemia, moderate hypoxemia, and severe hypoxemia. The important point is that a greater decrease in energy state is required in order to stimulate a given oxygen uptake when the oxygen delivery is low. Note especially the two points indicated by arrows. The oxygen uptake is approximately the same, but a much lower energy state is required with moderate hypoxemia in comparison to normoxemia.

Redrawn with permission from Hogan, M. C., P. G. Arthur, D. E. Bebout, P. W. Hochachka, and P. D. Wagner. Role of O2 in regulating tissue respiration in dog muscle working in situ. J. Appl. Physiol. 73: 728–736, 1992
Figure 6. Figure 6.

Illustration of a hypothetical intracellular lactate shuttle. Lactate produced in the cytosol might diffuse to mitochondria where the [La] is lower because of lactate consumption. At the mitochondria, the LDH reaction would operate to produce pyruvate and NADH from lactate and NAD+. Due to the higher concentration of lactate in comparison to pyruvate and NADH, such a shuttle might enhance the delivery of pyruvate and reducing equivalents to the mitochondria, particularly during exercise.

Figure 7. Figure 7.

L(+)‐lactate influx into sarcolemmal vesicles. Curve is best fit to Michaelis‐Menten hyperbolic function. Vmax = 139.4 nmol · mg−1 · min−1; Km = 40.1 mM.

Redrawn with permission from Roth, D. A., and G. A. Brooks. Lactate transport is mediated by a membrane‐bound carrier in rat skeletal muscle sarcolemmal vesicles. Arch. Biochem. Biophys. 279: 377–385, 1990
Figure 8. Figure 8.

Schematic of proposed model for the monocarboxylate carrier of lactate transport in red blood cells . Lactate transport in sarcolemmal vesicles has been proposed to be qualitatively similar . The various K's represent binding rates while the k's represent translocation rates. It is postulated that the carrier first binds H+ and then lactate. The carrier with only H+ bound is believed to be either immobile or else translocates only very slowly. See text for additional details.

Redrawn with permission from Poole, R. C., and A. P. Halestrap. Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am. J. Physiol. 264 (Cell Physiol. 33): C761–C782, 1993
Figure 9. Figure 9.

Net lactate uptake by canine gastrocnemius in situ at rest and during contractions (twitches at 4 Hz) at a high metabolic rate with increasing plasma [La]. Two points are important: (1) with increasing [La], net lactate uptake approaches a plateau; and (2) net lactate uptake is higher with the higher metabolic rate of contractions.

Redrawn with permission from Gladden, L. B., R. E. Crawford, and M. J. Webster. Effect of lactate concentration and metabolic rate on net lactate uptake by canine skeletal muscle. Am. J. Physiol. 266 (Regulatory Integrative Comp. Physiol. 35): R1095–R1101, 1994
Figure 10. Figure 10.

Total lactate influx via all three parallel pathways of lactate transport in the RBCs of “athletic” (equine and canine) and “nonathletic” (bovine and caprine) species. Lactate influx was much more rapid in the RBCs of the “athletic” species.

Redrawn with permission from Skelton, M. S., D. E. Kremer, E. W. Smith, and L. B. Gladden. Lactate influx into red blood cells of “athletic” and “nonathletic” species. Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R1121–R1128, 1995
Figure 11. Figure 11.

Blood [La] responses to exercise at high altitude in unacclimatized (acute hypoxia) and acclimatized subjects (chronic hypoxia) exposed to altitudes (429 mm Hg, unacclimatized; 347 mm Hg, acclimatized) resulting in the same arterial O2 pressure in both groups (33–35 mm Hg).

Based on data from Wagner et al. and Sutton et al. and redrawn with permission from Reeves, J. X, E. E. Wolfel, H. J. Green, R. S. Mazzeo, A. J. Young, J. R. Sutton, and G. A. Brooks. Oxygen transport during exercise at altitude and the lactate paradox: lessons from Operation Everest II and Pikes Peak. Exerc. Sport Sci. Rev. 20: 275–296, 1992
Figure 12. Figure 12.

Maximal blood [La] following exhaustive exercise in high‐altitude natives and acclimatized sea level natives (data combined). Note that maximal blood [La] declines as altitude increases.

Data are from Cerretelli et al. and West et al. and are redrawn with permission from West, J. B. Acid–base status and blood lactate at extreme altitude. In: Hypoxia, Metabolic Acidosis, and the Circulation, edited by A. I. Arieff. New York: Oxford University Press, 1992, p. 33–44
Figure 13. Figure 13.

Arterial blood [La] values at rest and during 45 min of submaximal exercise in control and β‐blocked subjects at sea level, acute, and chronic altitude exposure at 4300 m. Note that β‐blockade caused a reduction in [La] under all conditions including acute exposure. Also, note that acclimatization (chronic altitude) resulted in a decrease in [La] in both control and β‐blockade groups.

Redrawn with permission from Mazzeo, R. S., G. A. Brooks, G. E. Butterfield, A. Cymerman, A. C. Roberts, M. Selland, E. E. Wolfel, and J. T. Reeves. β‐Adrenergic blockade does not prevent the lactate response to exercise after acclimatization to high altitude. J. Appl. Physiol. 76: 610–615, 1994


Figure 1.

Relationship between oxygen consumption and partial pressure of oxygen in mitochondria isolated from rat heart. Note that oxygen consumption is maximal down to very low partial pressures. Other techniques have shown that mitochondrial oxygen consumption is independent of oxygen partial pressure down to ∼0.5 mm Hg. See text for details.

Redrawn with permission from Rumsey, W. L., C. Schlosser, E. M. Nuutinen, M. Robiolio, and D. F. Wilson. Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat. J. Biol. Chem. 265: 15392–15399, 1990


Figure 2.

Schematic illustration of relationship between lactate rate of appearance, lactate rate of disappearance, and resulting blood [La] during progressive, incremental exercise.

Redrawn with permission from Brooks, G. A. Anaerobic threshold: review of the concept and directions for future research. Med. Sci. Sports Exerc. 17: 22–31, 1985


Figure 3.

Predicted dependence of mitochondrial oxygen consumption on partial pressure of oxygen at high‐ and low‐energy states with constant [NAD+]/[NADH] of 1.0. Note that oxygen independence is preserved to low partial pressures when energy state is low.

Based on mathematical models of, and redrawn with permission from, Wilson, D. F., C. S. Owen, and M. Erecinska. Quantitative dependence of mitochondrial oxidative phosphorylation on oxygen concentration: a mathematical model. Arch. Biochem. Biophys. 195: 494–504, 1979


Figure 4.

Predicted dependence of mitochondrial oxygen consumption on partial pressure of oxygen at high and low [NAD+]/[NADH] with constant [ATP]/[ADP][Pi] of 500 · M−1. Note that oxygen independence is preserved to low partial pressures when [NAD+]/[NADH] is low.

Based on mathematical models of, and redrawn with permission from, Wilson, D. F., C. S. Owen, and M. Erecinska. Quantitative dependence of mitochondrial oxidative phosphorylation on oxygen concentration: a mathematical model. Arch. Biochem. Biophys. 195: 494–504, 1979


Figure 5.

Relationship between energy state and oxygen uptake in dog gastrocnemius muscle in situ at rest and two stimulation rates for normoxemia, moderate hypoxemia, and severe hypoxemia. The important point is that a greater decrease in energy state is required in order to stimulate a given oxygen uptake when the oxygen delivery is low. Note especially the two points indicated by arrows. The oxygen uptake is approximately the same, but a much lower energy state is required with moderate hypoxemia in comparison to normoxemia.

Redrawn with permission from Hogan, M. C., P. G. Arthur, D. E. Bebout, P. W. Hochachka, and P. D. Wagner. Role of O2 in regulating tissue respiration in dog muscle working in situ. J. Appl. Physiol. 73: 728–736, 1992


Figure 6.

Illustration of a hypothetical intracellular lactate shuttle. Lactate produced in the cytosol might diffuse to mitochondria where the [La] is lower because of lactate consumption. At the mitochondria, the LDH reaction would operate to produce pyruvate and NADH from lactate and NAD+. Due to the higher concentration of lactate in comparison to pyruvate and NADH, such a shuttle might enhance the delivery of pyruvate and reducing equivalents to the mitochondria, particularly during exercise.



Figure 7.

L(+)‐lactate influx into sarcolemmal vesicles. Curve is best fit to Michaelis‐Menten hyperbolic function. Vmax = 139.4 nmol · mg−1 · min−1; Km = 40.1 mM.

Redrawn with permission from Roth, D. A., and G. A. Brooks. Lactate transport is mediated by a membrane‐bound carrier in rat skeletal muscle sarcolemmal vesicles. Arch. Biochem. Biophys. 279: 377–385, 1990


Figure 8.

Schematic of proposed model for the monocarboxylate carrier of lactate transport in red blood cells . Lactate transport in sarcolemmal vesicles has been proposed to be qualitatively similar . The various K's represent binding rates while the k's represent translocation rates. It is postulated that the carrier first binds H+ and then lactate. The carrier with only H+ bound is believed to be either immobile or else translocates only very slowly. See text for additional details.

Redrawn with permission from Poole, R. C., and A. P. Halestrap. Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am. J. Physiol. 264 (Cell Physiol. 33): C761–C782, 1993


Figure 9.

Net lactate uptake by canine gastrocnemius in situ at rest and during contractions (twitches at 4 Hz) at a high metabolic rate with increasing plasma [La]. Two points are important: (1) with increasing [La], net lactate uptake approaches a plateau; and (2) net lactate uptake is higher with the higher metabolic rate of contractions.

Redrawn with permission from Gladden, L. B., R. E. Crawford, and M. J. Webster. Effect of lactate concentration and metabolic rate on net lactate uptake by canine skeletal muscle. Am. J. Physiol. 266 (Regulatory Integrative Comp. Physiol. 35): R1095–R1101, 1994


Figure 10.

Total lactate influx via all three parallel pathways of lactate transport in the RBCs of “athletic” (equine and canine) and “nonathletic” (bovine and caprine) species. Lactate influx was much more rapid in the RBCs of the “athletic” species.

Redrawn with permission from Skelton, M. S., D. E. Kremer, E. W. Smith, and L. B. Gladden. Lactate influx into red blood cells of “athletic” and “nonathletic” species. Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R1121–R1128, 1995


Figure 11.

Blood [La] responses to exercise at high altitude in unacclimatized (acute hypoxia) and acclimatized subjects (chronic hypoxia) exposed to altitudes (429 mm Hg, unacclimatized; 347 mm Hg, acclimatized) resulting in the same arterial O2 pressure in both groups (33–35 mm Hg).

Based on data from Wagner et al. and Sutton et al. and redrawn with permission from Reeves, J. X, E. E. Wolfel, H. J. Green, R. S. Mazzeo, A. J. Young, J. R. Sutton, and G. A. Brooks. Oxygen transport during exercise at altitude and the lactate paradox: lessons from Operation Everest II and Pikes Peak. Exerc. Sport Sci. Rev. 20: 275–296, 1992


Figure 12.

Maximal blood [La] following exhaustive exercise in high‐altitude natives and acclimatized sea level natives (data combined). Note that maximal blood [La] declines as altitude increases.

Data are from Cerretelli et al. and West et al. and are redrawn with permission from West, J. B. Acid–base status and blood lactate at extreme altitude. In: Hypoxia, Metabolic Acidosis, and the Circulation, edited by A. I. Arieff. New York: Oxford University Press, 1992, p. 33–44


Figure 13.

Arterial blood [La] values at rest and during 45 min of submaximal exercise in control and β‐blocked subjects at sea level, acute, and chronic altitude exposure at 4300 m. Note that β‐blockade caused a reduction in [La] under all conditions including acute exposure. Also, note that acclimatization (chronic altitude) resulted in a decrease in [La] in both control and β‐blockade groups.

Redrawn with permission from Mazzeo, R. S., G. A. Brooks, G. E. Butterfield, A. Cymerman, A. C. Roberts, M. Selland, E. E. Wolfel, and J. T. Reeves. β‐Adrenergic blockade does not prevent the lactate response to exercise after acclimatization to high altitude. J. Appl. Physiol. 76: 610–615, 1994
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L. Bruce Gladden. Lactate Transport and Exchange During Exercise. Compr Physiol 2011, Supplement 29: Handbook of Physiology, Exercise: Regulation and Integration of Multiple Systems: 614-648. First published in print 1996. doi: 10.1002/cphy.cp120114