From Waste to Fuel.
New insights into the function of lactate in physiology

 

Feature by

CDeuker

 

 

1       Content

1      Content

2      Abstract

3      References

4      End of Pipe – the former explanation

5      The Lactate Shuttle Revolution

2       Abstract

Lately I read a paper about new insights into the function of lactate that really thrilled me [Wahl, P.; 2009]. In this paper, everything I learned at University about energy physiology in muscles was upside down and together with this new paradigm, some problems between theory and practical experiences we used to discuss vanished instantly.

This S2n – Feature describes the new Lactate Shuttle physiology [s. Brooks, G. A.; 1985b] in contrast to the former theory of muscle energy metabolisms. Beginning with a short review to the old theory of muscle physiology, the radical change to these findings of lactate shuttle illustrate the new paradigm. The aim of this feature is not to recapitulate all details of contemporary research in physiology, but to point out the fundamental effects of the lactate shuttle to physiology with regard to energy consumption.

3       References

Brooks, G. A.; 1985a; “Anaerobic threshold: review of the concept and directions for future research”; 22-31; Medicine & Science in Sports & Exercise; 0195-9131; 17/1; http://journals.lww.com/acsm-msse/Fulltext/1985/02000/Anaerobic_threshold__review_of_the_concept_and.5.aspx

Brooks, G. A.; 1985b; “Lactate:Glycolytic End Product and Oxidative Substrate During Sustained Exercise in Mammals — The “Lactate Shuttle””; 208-218; In: Gilles, R.;”Circulation, Respiration, and Metabolism: Current Comparative Approaches”; Berlin, Heidelberg; Springer Berlin Heidelberg

Brooks, G. A.; 2002; “Lactate shuttles in nature”; 258-264; Biochemical Society Transactions; 0300-5127 (Print); 30/part 2;

Brooks, G. A.; 2007; “Lactate. Link Between Glycolytic and Oxidative Metabolism”; 341-343; Sports Medicine; 1179-2035; 37/4; http://dx.doi.org/10.2165/00007256-200737040-00017

Cruz, R. S. d. O.; de Aguiar, R. A.; Turnes, T.; Penteado Dos Santos, R.; Fernandes Mendes de Oliveira, M.; Caputo, F.; 2012; “Intracellular Shuttle: The Lactate Aerobic Metabolism”; 420984; The Scientific World Journal; 1537-744X; 2012/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345575/

de Marées, H.; 1992; “Sportphysiologie”; Köln-Mülheim; Tropon-Werke;

Gladden, L. B.; 2004; “Lactate metabolism: a new paradigm for the third millennium”; 5-30; The Journal of Physiology; 1469-7793; 558/1; http://dx.doi.org/10.1113/jphysiol.2003.058701

Holfelder, B.; Bubeck, D.; 2012; “Theoretische Betrachtungen über die Trainingssteuerung anhand des Laktatstoffwechsels und der Muskelfasertypisierung”; 32-39; Schweizerische Zeitschrift für «Sportmedizin und Sporttraumatologie»; 1022-6699, online 1422-0644; 60/1;

Knechtle, B.; 2002; “Sportphysiologie: Leistung und Ernährung im Sport”; Basel, Freiburg, Paris, London, New York, New Delhi, Bankok, Singapore, Tokyo, Sydney; Karger; 3-8055-7457-6

Küster, L.; 2009; “Leistungsdiagnostik in Sportmedizin und Sportwissenschaft”; Saabrücken; VDM Verlag Dr. Müller; 978-3-639-17437-3

Laube, W.; 2009a; “Diagnostik der Leistungen des sensomotorischen Systems: Koordination – ausdauer – Kraft”; 228-274; In: Laube, W.;”Sensomotorisches System”; Stuttgart; Thieme Verlag

Laube, W.; 2009b; “Logistiksysteme des sensomotorischen Systems: die funktionelle Kette der aeroben Energieversorgung – Regulationssysteme der Homöoestase und der Koordination der Organfunktionen”; 118-164; In: Laube, W.;”Sensomotorisches System”; Stuttgart; Thieme Verlag

Tomasits, J.; Haber, P.; 2011; “Leistungsphysiologie. Grundlagen für Trainer, Physiotherapeuten und Masseure”; Wien; SpringerWienNewYork; 978-3-7091-0436-1

Wahl, P.; 2009; “Moderne Betrachtungsweisen des Laktats : Laktat ein überschätztes und zugleich unterschätztes Molekül”; 100-107; Schweizerische Zeitschrift für «Sportmedizin und Sporttraumatologie»; 1022-6699, online 1422-0644; 57/3; http://www.sgsm.ch/publikationen/swiss-sports-exercise-medicine/

 

4       End of Pipe – the former explanation

The fitness hype got a tremendous push recently by wearables like fitness trackers. For athletes all these are only additionally information, nice to have, but dominated by one variable – the heart rate. One reason is that the heart rate is easy to measure even in action. More significant, beyond all this information to movement and acceleration, the heart rate is directly connected to performance capabilities of the body. And the idea of training is to push up exercise performance to an higher level. The question is how to do this efficiently with regard to exhaustion and energy resources. Out of experience in sports as well as the classification of different competitions, it is obvious that there are two realms – sprint and endurance. That is exactly what muscle physiology tells with fast and slow switching muscle fibers and many mixtures of these structures. The fast switching fibers can quickly contract and produce powerful forces with a high exhaustion rate and vice versa the slow switching fibers. Because this feature focuses on energy metabolisms and not anatomic specification of muscles, no further explanations to this vast and interesting field follows.

Similarly to the muscle anatomy, the metabolisms of energy are divided in two different realms: aerobic and anaerobic which describe the way of phosphate recycling. In muscles, as in every cell, energy is used in forms of phosphate like ATP (Adenosine triphosphate). In contrast to modern agriculture, the evolution discovered that phosphate is limited and scares in nature and developed extremely effective processes in phosphate recycling. Our energy resources of carbs, fat or proteins are used for this phosphate recycling in the Krebs-Cycle and the respiration chain [s. Laube, W.; 2009b; 141].

Lactate is connected to phosphate recycling through glycolysis, which plays a prominent role because it can be aerobic as well as anaerobic [s. Tomasits, J.; Haber, P.; 2011; 18-19]. Only in the anaerobic situation lactate is built up from pyruvate that is the product of glycolysis [s. de Marées, H.; 1992; 411]. With aerobic conditions pyruvate is activated to Acetyl Coenzyme A (acetyl-CoA) with an oxidative decarboxylation and transferred to the Krebs-Cycle [s. Laube, W.; 2009b; 142].

In the former explanation, initiated by Louis Pasteur, lactate appearance was caused by the lack of oxygen during contraction and is followed by fatigue and damage to muscle tissues [s. Brooks, G. A.; 2007; 341 / Wahl, P.; 2009; 101]. Only few authors today mention that lactate is built up because of an oxygen deficit [s. Knechtle, B.; 2002; 131]. The main aspect of anaerobic glycolysis in newer publications is a faster phosphate recycling because of fewer process steps [s. de Marées, H.; 1992; 410] and a location inside the plasma of energy consuming muscle cells [s. de Marées, H.; 1992; 412]. Some authors mention lactate as an energy source for skeletal muscles [s. de Marées, H.; 1992; 409 / Küster, L.; 2009; 68 / Laube, W.; 2009a; 250 / Tomasits, J.; Haber, P.; 2011; 31], but this topic is not discussed or considered in energy calculations.

The common description of lactate is that of a dead end waste metabolite of glycolysis [s. de Marées, H.; 1992; 409 / Knechtle, B.; 2002; 30 / Laube, W.; 2009b; 144 / Tomasits, J.; Haber, P.; 2011; 49] causing acidosis. It is mentioned that lactate is utilized in recovery periods [s. Knechtle, B.; 2002; 30-31] from liver, heart or kidney [s. Tomasits, J.; Haber, P.; 2011; 15]. Although some authors mention the capability of lactate usage in other tissues and even in skeletal muscles, it is not illustrated as internal energy resource.

5       The Lactate Shuttle Revolution

The Lactate Shuttle Revolution started with findings through new analysis methods in physiology, showing that lactate is built up in rest as well as under exercise conditions in muscles [s. Brooks, G. A.; 1985b; 208]. Out of the former perspective to muscle physiology, in resting situations the more effective aerobe energy process should occur. Lactate production in rest is not compatible with the idea of a highly efficient aerobe energy metabolism without lactate in contrast to a less efficient, but fast anaerobic process in muscles.

Another surprising result showed lactate production under fully oxidative conditions [s. Brooks, G. A.; 2007; 342] affecting the argumentation of anaerobic metabolisms for lactate formation. With these findings, a fundamental disjunction of aerobic and anaerobic metabolisms, even running simultaneously, were no longer obvious.

Lactate clearance in exercise and not only in rest was already mentioned before the lactate shuttle revolution, as described in the previous section, but this aspect was not taken into account to rethink the disjunctive energy metabolisms. The rebuilding of lactate to pyruvate through the Cori Cycle in the liver is only a minor fraction of approximately 10-25% [Brooks, G. A.; 2002; 261] in contrast to 75% of lactate oxidation in exercise [Brooks, G. A.; 2007; 342]. With these percentages, it is obvious, that lactate utilization is common and lactate levels are not an exception caused by a high workload.

This is the main aspect of the lactate shuttle revolution: lactate is commonly utilized as a fuel and is not a dead end waste product.

This lactate turnover to utilization has two different aspects of intra- and inter-cellular metabolisms that are called ‘shuttles’ [Brooks, G. A.; 2002; 259]. There are many different shuttles for lactate usage in liver, heart, brain, red blood cells and different skeletal muscles types and Gladden choose the right heading for it: “shuttles, shuttles, everywhere” [Gladden, L. B.; 2004; 8].

The utilization of lactate in skeletal muscles changes in oxidative red fibers as well as in glycolic white fibers to input for oxidation [s. Gladden, L. B.; 2004; 8]. This enhanced lactate usage takes place at 1-2 mmol/l in slow twitching fibers (ST) and at 3-4mmol/l in fast twitching fibers (FT) [s. Wahl, P.; 2009; 102]. Note here, that these concentrations are inside muscle cells and not blood lactate, which is the overall result of lactate usage and production. Classical lactate analysis in performance diagnostics measure only blood lactate as a sum of unknown production and utilization. The overall level of blood lactate is still increasing with higher workloads and through the size principle of motor pool neurons recruiting more FT fibers with higher frequencies [s. Brooks, G. A.; 1985a; 28].

The detailed metabolism process of intra-cellular lactate shuttle is still under scientific debate. Different steps for lactate usage are currently studied in scientific research: (1) direct uptake of lactate by mitochondria and oxidation; (2) oxidation of lactate by lactate dehydrogenase enzyme (LDH) in the intermembrane space of muscle cells and (3) the way lactate is transported through membranes by monocarboxylate transporters (MCT) [s. Gladden, L. B.; 2004; 10]. Latest research indicate a mitochondrial oxidation metabolism as a crucial energy source [s. Cruz, R. S. d. O., et al.; 2012; 6] which is straight forward with the fundamental idea of a intracellular lactate shuttle. This way of energy utilization seems to be a major channel in exercise, even for extreme endurance [s. Brooks, G. A.; 2007; 342]. For a classical skilled sports scientist like me, this sound revolutionary, turning all fundamental theories about muscle energy physiology upside down.

The other paradigmatic change with the lactate shuttle revolution is the recognition that lactate “… acts as a kind of ‘bargaining chip’ between tissues, a moving glycogen, which is able to provide raw material for ATP resynthesis in mitochondria of a wide variety of body cells” [Cruz, R. S. d. O., et al.; 2012; 6]. Out of a muscle physiological perspective, this connection of ST and FT fibers through energy transmission provides a new argumentation for training techniques such as high intensity training (HIT) [s. Holfelder, B.; Bubeck, D.; 2012; 34]. Consequences for training of the lactate shuttle revolution will be discussed in the next S2n-Feature coming soon. It is crucial to point out the paradigmatic change in the end of the separation of anaerobic and aerobic energy metabolism – either for intra- or inter-cellular shuttles.

The past discussions about the magnitude and analysis of an anaerobic threshold fades in the light of the lactate shuttle revolution. All argumentation about static or individual anaerobic thresholds, dominating the scientific discourse for a long time, are demonstrably false [s. Brooks, G. A.; 2002; 263] and converted into an continuous flux. Especially the strict distinction between sprint and endurance are weakened in analysis and performance [s. Gladden, L. B.; 2004; 23]. On the other hand, it is obvious that lactate is a crucial metabolite in muscle energy metabolisms, making it highly interesting for performance analysis.