Lactate turnover in fast-moving vertebrates : the control of plasma metabolite fluxes
Creators: name: Weber, Jean-Michel
Publisher: name: University of British Columbia
Year: 2010

description: During sustained exercise, working muscles must be supplied with adequate kinds and amounts of exogenous fuels, and the delivery rates of oxygen and oxidizable substrates should be matched. The study of metabolite fluxes and their regulation is therefore critical to the understanding of exercise metabolism. Lactate has received renewed attention from physiologists and biochemists with the realization that it is not only an end product of glycolysis, but also an important fuel for aerobic work. As an oxidizable fuel, this substrate may provide some performance advantage over other fuels such as glucose and free fatty acids. The goals of this thesis were: 1) to determine whether endurance-adapted animals can support higher plasma lactate turnover rates than sedentary animals; and 2) to investigate the major factors involved in the regulation of plasma metabolite turnover at the whole-organism level - using lactate as a model. Lactate turnover rates were measured by bolus injection of [U-¹⁴C]lactate in skipjack tuna, Katsuwonus pelamis, and in thoroughbred racehorses, Equus caballus. In tuna, turnover rates ranged from 112 to 431 umol min⁻¹ kg⁻¹ and they were positively correlated with lactate concentration (slope = 15.1, r = 0.92). This teleost is able to support higher plasma lactate turnover rates than expected for a mammalian lower temperature, and lactate is probably an important oxidizable fuel in this species. For comparative purposes, resting turnover rates of lactate and glucose were plotted versus body mass on a log-log scale for a wide range of mammalian species. These plots were linear, and they showed the same slope as the classic body mass vs metabolic rate relationship. Thoroughbred horses are likely to have an aerobic scope of 40-fold or more. One of their main physiological adaptations to exercise is the ability to increase hematocrit by more than one and a half-fold in response to exercise. In the present study, this adjustment allowed them to reach an A-V difference in 0₂ content of more than 23 vol% during maximal exercise, a much higher value than other mammals. Their lactate turnover rate and cardiac output were measured at rest and two levels of submaximal exercise (45 and 55 V0₂ max) to investigate the relationship between cardiovascular adjustments on plasma lactate turnover rate. Cardiac output ranged from 106 to 571 ml min⁻¹ kg⁻¹, and mean lactate turnover rate from 9.3 at rest, to 75.9 umol min⁻¹ kg⁻¹ at 55% V0₂ max. In contrast with the situation found in tuna, the lactate turnover rates of thoroughbreds were not elevated compared with other mammals, showing that the metabolic adaptations of these outstanding athletes do not include the ability to sustain higher lactate fluxes than sedentary animals. In horses, the contribution of plasma lactate oxidation to V0₂ is minimal, and this substrate is not an important oxidative fuel; lipid oxidation may represent their major pathway for aerobic energy production during exercise. The ability to oxidize plasma lactate at high rates is therefore not necessarily required for the "elite" performance of endurance exercise. This study also shows that both, plasma lactate concentration and cardiac output are positively correlated with turnover rate. The correlation between cardiac output and lactate turnover rate is independent of the relationship between plasma lactate concentration and turnover rate. Plasma metabolite concentration and cardiac output can be regulators of plasma metabolite turnover rate. It is proposed that these two variables are, respectively, the fine and coarse controls for flux rate adjustments during exercise.