So i have noticed haidut sees sirtuins as unfavorable but sirt3 specifically seems favorable does it not?
SIRT3 (Sirtuin 3) is the primary mitochondrial deacetylase that increases Pyruvate Dehydrogenase (PDH) activity over Pyruvate Dehydrogenase Kinase (PDK).
It does this through the following mechanisms:
Deacetylation of PDHA1: SIRT3 interacts with and deacetylates the E1 alpha subunit of PDH (PDHA1) at specific lysine residues (such as K321 in cancer cells, K336 in skeletal muscle, or K83 in other tissues), which directly increases PDH enzymatic activity.
Reversing the Warburg Effect: SIRT3 acts as a tumor suppressor in several cancers by promoting the shift from glycolysis to oxidative phosphorylation, which reduces lactate production.
Conversely, a lack of SIRT3 (SIRT3 deletion) leads to hyperacetylation of PDHA1, increased PDK activity, and decreased PDH activity, which promotes a metabolic shift towards glycolysis.
a lack of SIRT3 (SIRT3 deletion or knockdown) leads to the hyperacetylation of mitochondrial proteins, specifically the pyruvate dehydrogenase E1α subunit (PDHA1). This hyperacetylation, often occurring at residues such as K321 or K83, leads to reduced activity of the pyruvate dehydrogenase complex (PDH) and increased activity of pyruvate dehydrogenase kinase (PDK), which further inactivates PDH.
Consequently, this inhibition of PDH restricts the entry of pyruvate into the tricarboxylic acid (TCA) cycle, prompting a metabolic shift towards glycolysis and increased lactate production (often called the Warburg effect).
SIRT3 is pro-NAD+, favoring an elevated NAD+/NADH ratio through its enzymatic activity.
@haidut
