Is pyrucet flawed?
-
I felt a little lazy asked ai about acac/bhb ratio. While raising it with exogenous acac (from pyrucet) can raise nad/nadh and it may still inhihit pdh apparently?
Exogenous AcAc raising the NAD⁺/NADH ratio could indirectly decrease PDH activity by favoring PDK-mediated phosphorylation, despite the more oxidized redox state.PDH/PDK RegulationPDH activity is inhibited when phosphorylated by PDK, which is activated by high acetyl-CoA/CoA and NADH/NAD⁺ ratios but suppressed by an oxidized state (high NAD⁺/NADH). � AcAc metabolism generates acetyl-CoA via conversion to Acetoacetyl-CoA and then acetyl-CoA, elevating this ratio and overriding the NAD⁺ benefit to activate PDK. �Ketone Effects on FluxStudies in muscle mitochondria show AcAc directly reduces PDH flux, dependent on TCA intermediates like 2-oxoglutarate, via feedback inhibition and lower active PDH content. � This aligns with ketone sparing glucose oxidation by suppressing PDH, even as NAD⁺ rises from BDH1 activity.Net ImpactOverall, PDH activity likely falls (PDH/Pdk ratio decreases), as acetyl-CoA elevation dominates in ketotic states, promoting mitochondrial fat oxidation over pyruvate entry. �
-
@user73636 if the study you mention is indeed true, it's not clear if it would still be valid for Pyrucet specifically because it includes the ethyl pyruvate to replenish the PDH that the EA would reportedly inhibit.
