Substrate-Dependent Sensitivity of SIRT1 to Nicotinamide Inhibition.

ABSTRACT: SIRT1 is the most extensively studied human sirtuin with a broad spectrum of endogenous targets. It has been implicated in the regulation of a myriad of cellular events, such as gene transcription, mitochondria biogenesis, insulin secretion as well as glucose and lipid metabolism. From a mechanistic perspective, nicotinamide (NAM), a byproduct of a sirtuin-catalyzed reaction, reverses a reaction intermediate to regenerate NAD⁺ through "base exchange", leading to the inhibition of the forward deacetylation. NAM has been suggested as a universal sirtuin negative regulator. Sirtuins have evolved different strategies in response to NAM regulation. Here, we report the detailed kinetic analysis of SIRT1-catalyzed reactions using endogenous substrate-based synthetic peptides. A novel s

SUBMITTER: Rymarchyk S 

PROVIDER: S-EPMC7922766 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature