Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)


Medical Sciences


Dr. G.J.F. Heigenhauser


Moderate to high intensity exercise generates lactate and hydrogen ions which accumulate in both blood and muscle and are thought to contribute to the development of fatigue. Alteration in the extracellular pH has been shown to influence the appearance of lactate in plasma, acidosis decreasing and alkalosis increasing blood lactate concentration. The present research was designed to explore the potential mechanisms by which acid-base alterations influence lactate production and the associated metabolic changes in exercise. Normal subjects took part in two studies. Acidosis induced by ingestion of ammonium chloride and alkalosis via ingestion of sodium bicarbonate were compared to control during rest and exercise. Needle biopsies of the vastus lateralis muscle, blood flow and arterial and femoral venous blood samples were taken. Acidosis resulted in decreased lactate production and efflux, secondary to decreased glycogenolysis from reduced transformation of glycogen phosphorylase to its active form and the lack of accumulation of positive allosteric modulators. Lower glycogen utilization resulted and was associated with an increase in free fatty acid (FFA) utilization from intramuscular stores. Pyruvate dehydrogenase activity was lower. Alkalosis had opposite effects: greater lactate production, efflux, glycogenolysis, pyruvate dehydrogenase activity and glycogen utilization, with lower FFA utilization. However, the increased glycogenolysis resulted from allosteric activation of glycogen phosphorylase through increases in the concentration of its positive modulators adenosine monophosphate and substrate free inorganic phosphate. These studies conclude that alterations in lactate production result entirely from a mismatch in the catalytic rates of glycogen phosphorylase and pyruvate dehydrogenase. Additionally, these studies identified for the first time the mechanisms responsible for the complex interplay of regulatory enzyme activity, fuel utilization and the importance of acid-base homeostasis in its control.

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