Is pyrucet flawed?
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I felt a little lazy asked ai about acac/bhb ratio. While raising it with exogenous acac (from pyrucet) can raise nad/nadh 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. �