A Thereotical combination for inhibition of warburg effect
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Exogenous pyruvate, oxaloacetate, and PQQ each influence lactate dehydrogenase A (LDHA) activity, primarily by modulating the pyruvate-to-lactate conversion in glycolysis.
Pyruvate effects
Exogenous Pyruvate Effects High millimolar concentrations of exogenous pyruvate cause substrate inhibition of LDHA, reducing its conversion of pyruvate to lactate in both enzymatic assays and live cells.PQQ Effects
Pyrroloquinoline quinone (PQQ) binds directly to LDH, inhibiting the forward reaction (pyruvate + NADH → lactate + NAD⁺) while enhancing the reverse (lactate → pyruvate). This occurs via PQQ's redox activity, oxidizing NADH to NAD⁺, which shifts LDH equilibrium toward pyruvate production and reduces cellular lactate release.Oxaloacetate effects
acts as a competitive inhibitor of lactate dehydrogenase A (LDHA), blocking pyruvate conversion to lactate and reducing glycolytic flux. This elevates the NAD+/NADH ratio, curbs lactate production, and promotes TCA cycle entry of pyruvateSynergistic Mechanisms
PQQ binds LDHA and oxidizes NADH to NAD⁺ through redox cycling, inhibiting the forward reaction (pyruvate → lactate) and strongly enhancing the reverse (lactate → pyruvate). Oxaloacetate competitively inhibits LDHA's forward activity, reducing lactate production and diverting pyruvate to the TCA cycle. High-dose exogenous pyruvate induces substrate inhibition of LDHA, further blocking lactate formation in an MCT1-dependent manner.Role of Exogenous NAD and nad precursors
Exogenous NAD⁺ boosts the NAD⁺/NADH ratio, amplifying PQQ's redox effect and LDH equilibrium shift toward pyruvate production. This combination elevates cytosolic NAD⁺, curbing Warburg glycolysis and promoting OXPHOS, as seen in reduced lactate release and higher ATP in cell models.Expected Outcomes Together, they lower pyruvate-to-lactate flux (via inhibition) and increase lactate-to-pyruvate (via enhanced reverse kinetics), normalizing metabolic ratios like lactate/pyruvate.
Obviously focus on the basics first
Thiamine,magnesium,calcium for pyruvate dehydrogenase activation. Another combo that could activate pdh and enhance glucose oxidation is actovegin + meldonium aswell as Cardihaler for enhanced bohr effect for better mitochondrial oxygenation to lower lactate and shift towards more efficient metabolism -
@user73636 said in A Thereotical combination for inhibition of warburg effect:
Pyrroloquinoline quinone
I quite like Pyrroloquinoline quinone, and it does make me ravenous.