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πŸ“ Lactate Is Always The End Product Of Glycolysis

Through much of the history of metabolism, lactate (Laβˆ’) has been considered merely a dead-end waste product during periods of dysoxia. Congruently, the end product of glycolysis has been viewed dichotomously: pyruvate in the presence of adequate oxygenation, Laβˆ’ in the absence of adequate oxygenation. In contrast, given the near-equilibrium nature of the lactate dehydrogenase (LDH) reaction and that LDH has a much higher activity than the putative regulatory enzymes of the glycolytic and oxidative pathways, we contend that Laβˆ’ is always the end product of glycolysis. Cellular Laβˆ’ accumulation, as opposed to flux, is dependent on (1) the rate of glycolysis, (2) oxidative enzyme activity, (3) cellular O2 level, and (4) the net rate of Laβˆ’ transport into (influx) or out of (efflux) the cell. For intracellular metabolism, we reintroduce the Cytosol-to-Mitochondria Lactate Shuttle. Our proposition, analogous to the phosphocreatine shuttle, purports that pyruvate, NAD+, NADH, and Laβˆ’ are held uniformly near equilibrium throughout the cell cytosol due to the high activity of LDH. Laβˆ’ is always the end product of glycolysis and represents the primary diffusing species capable of spatially linking glycolysis to oxidative phosphorylation.

Updated on June 7, 2020

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