NAD metabolite levels as a function of vitamins

NAD metabolite levels as a function of vitamins

Abstract
Background: NAD+ is a coenzyme for hydride transfer enzymes and a substrate for sirtuins and other NAD
+-dependent ADPribose transfer enzymes. In wild-type Saccharomyces cerevisiae, calorie restriction accomplished by
glucose limitation extends replicative lifespan in a manner that depends on Sir2 and the NAD+ salvage enzymes,
nicotinic acid phosphoribosyl transferase and nicotinamidase. Though alterations in the NAD+ to nicotinamide ratio
and the NAD+ to NADH ratio are anticipated by models to account for the effects of calorie restriction, the nature of
a putative change in NAD+ metabolism requires analytical definition and quantification of the key metabolites.
Results: Hydrophilic interaction chromatography followed by tandem electrospray mass spectrometry were used
to identify the 12 compounds that constitute the core NAD+ metabolome and 6 related nucleosides and
nucleotides. Whereas yeast extract and nicotinic acid increase net NAD+ synthesis in a manner that can account for
extended lifespan, glucose restriction does not alter NAD+ or nicotinamide levels in ways that would increase Sir2
activity.
Conclusions: The results constrain the possible mechanisms by which calorie restriction may regulate Sir2 and
suggest that provision of vitamins and calorie restriction extend lifespan by different mechanisms…

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