TY - JOUR
T1 - Lactate is always the end product of glycolysis
AU - Rogatzki, Matthew J.
AU - Ferguson, Brian S.
AU - Goodwin, Matthew L.
AU - Gladden, L. Bruce
N1 - Publisher Copyright:
© 2015 Rogatzki, Ferguson, Goodwin and Gladden.
PY - 2015
Y1 - 2015
N2 - Through much of the history of metabolism, lactate (La-) 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, La- 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 La- is always the end product of glycolysis. Cellular La- 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 La- 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 La- are held uniformly near equilibrium throughout the cell cytosol due to the high activity of LDH. La- is always the end product of glycolysis and represents the primary diffusing species capable of spatially linking glycolysis to oxidative phosphorylation.
AB - Through much of the history of metabolism, lactate (La-) 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, La- 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 La- is always the end product of glycolysis. Cellular La- 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 La- 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 La- are held uniformly near equilibrium throughout the cell cytosol due to the high activity of LDH. La- is always the end product of glycolysis and represents the primary diffusing species capable of spatially linking glycolysis to oxidative phosphorylation.
KW - Aerobic
KW - Anaerobic
KW - Cytosolic lactate shuttle
KW - Lactate dehydrogenase
KW - Mitochondria
KW - NADH
KW - Pyruvate
UR - http://www.scopus.com/inward/record.url?scp=84949116564&partnerID=8YFLogxK
U2 - 10.3389/fnins.2015.00022
DO - 10.3389/fnins.2015.00022
M3 - Article
C2 - 25774123
AN - SCOPUS:84949116564
SN - 1662-4548
VL - 9
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
IS - FEB
M1 - 22
ER -