I know that fasting leads to increased level of intracellular NAD and activation of SIRT1. But does anyone know the underlying mechanism relating fasting to NAD?
NADH production from NAD is basic to ATP synthesis in mitochondria. Fasting depletes the NADH production since ATP is still used. Thus fasting induces increased NAD cellular levels.
Yeah, Interesting! Fasting of cells leads to reduction of ATP. There are two typical ways in which ATP could be produced. It could be through (1) Substrate Level Phosphorylation (2) Oxidative phosphorylation. Now, Relating this two perspectives of ATP synthesis to your question, NAD would only produce ATP if converted to NADH + H+ through the Complexes of the ETC and then Chemiosmotic process driven by FoF1ATPase to yield 3 molecules of ATP (Oxidative phosphorylation). To hit the point, NADH would yield 3ATP.
In intermediary metabolism, NAD is involved in glycolysis, TCA cycle and beta-oxidation. During fasting, insulin level falls which implies the unavailability of blood glucose while glucagon level rises. The unavailability of blood glucose level implies the reduced activity of hexokinase and therefore inhibiting the downstream NAD which is the coenzyme for Glyceraldehyde III Phosphate Dehydrogenase (GAPDH). This implies the reduction in the production of ATP through oxidative phosphorylation reaction because there wont be electron transfer through NADH to Complex 1 of ETC and there wont be Gibbs free energy production to drive the reaction for the 3ATP production from one molecule of NADH. So, in a nutshell, during fasting condition, we have reduction in NADH and increase in NAD level which leaves Electron Transport Chain with less or no electrons to transfer thereby, leading to reduction in FoF1 ATPase activity for the production of ATP.
Thank you.
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