Oxaloacetate and PQQ as potent anti lactate agents
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Oxaloacetate (OAA) inhibits lactate dehydrogenase (LDH), lowering lactate by blocking pyruvate conversion to lactate. This spares NADH for oxidation back to NAD+ in mitochondria via shuttles.
OAA also directly oxidizes NADH to NAD+ through malate dehydrogenase (OAA to malate). Additionally, elevated OAA pulls acetyl-CoA into the TCA cycle via citrate synthase, lowering free acetyl-CoA—which reduces PDH inhibition (by product inhibition and PDK activation), thereby activating PDH—while raising free CoA.
Effects on Warburg Effect
OAA counters the Warburg effect by inhibiting LDH to cut lactate production, shifting metabolism from aerobic glycolysis toward oxidative phosphorylation.
NAD+/NADH Boost
OAA is converted to malate in the cytoplasm by malate dehydrogenase, consuming NADH to generate NAD+ and boosting the NAD+/NADH ratio by up to 900%, favoring pyruvate over lactate formation.
Reverses Metabolic Shifts In high-glycolysis states like cancer or chronic fatigue syndrome, OAA reduces excess lactic acid and lowers the lactate-to-pyruvate ratio, restoring oxidative metabolism.
Liver Injury Benefits
In liver damage models, OAA decreases lactic acid production to 53–85% of control levels, supporting metabolic recovery.PQQ counteracts lactate accumulation, Warburg metabolism, and reductive stress primarily by binding to lactate dehydrogenase (LDH) and shifting its equilibrium toward pyruvate production over lactate. This mechanism favors oxidative metabolism, reduces glycolytic reliance, and supports a more oxidized cellular state.
Anti-Lactate Action
PQQ oxidizes NADH to NAD+, inhibiting LDH's forward reaction (pyruvate → lactate) while enhancing the reverse (lactate → pyruvate). In cell studies, 50 nM PQQ cut lactate release by ~85% in fibroblasts, lowering lactate/pyruvate ratios and boosting ATP via TCA cycle entry.