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[100YearsToGo]

FYI.
Interesting study:

http://www.ncbi.nlm....2?dopt=Abstract

Particularly this part is interesting:

"Finally, a sirtuin-specific approach is considered that is called nicotinamide derepression. This approach is designed to antagonize physiologic nicotinamide inhibition of sirtuins as a means to upregulate sirtuin function."

Have your cake and...

Wonder how they will fool the enzyme (sirts)

Lets wait till the text is available.

[maxwatt]

FYI.
Interesting study:

http://www.ncbi.nlm....2?dopt=Abstract

Particularly this part is interesting:

"Finally, a sirtuin-specific approach is considered that is called nicotinamide derepression. This approach is designed to antagonize physiologic nicotinamide inhibition of sirtuins as a means to upregulate sirtuin function."

Have your cake and...

Wonder how they will fool the enzyme (sirts)

Lets wait till the text is available.

Look here for a related article: Structural Basis for Nicotinamide Inhibition and Base Exchange in Sir2 Enzymes

Brandi D. Sanders1, 2, Kehao Zhao1, James T. Slama3 and Ronen Marmorstein1, 2, ,

1The Wistar Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA

2Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA

3Department of Medicinal and Biological Chemistry, College of Pharmacy, University of Toledo, OH 43606, USA


Received 14 June 2006; revised 13 October 2006; accepted 27 December 2006. Published: February 8, 2007. Available online 8 February 2007.

Summary

The Sir2 family of proteins consists of broadly conserved NAD+-dependent deacetylases that are implicated in diverse biological processes, including DNA regulation, metabolism, and longevity. Sir2 proteins are regulated in part by the cellular concentrations of a noncompetitive inhibitor, nicotinamide, that reacts with a Sir2 reaction intermediate via a base-exchange reaction to reform NAD+ at the expense of deacetylation. To gain a mechanistic understanding of nicotinamide inhibition in Sir2 enzymes, we captured the structure of nicotinamide bound to a Sir2 homolog, yeast Hst2, in complex with its acetyl-lysine 16 histone H4 substrate and a reaction intermediate analog, ADP-HPD. Together with related biochemical studies and structures, we identify a nicotinamide inhibition and base-exchange site that is distinct from the so-called “C pocket” binding site for the nicotinamide group of NAD+. These results provide insights into the Sir2 mechanism of nicotinamide inhibition and have important implications for the development of Sir2-specific effectors.

Author Keywords: DNA; CELLCYCLE

Nampt agonists result in improved NAD+/NADH ration, associated with longevity. (resveratrol is one such agonist, according to a recent paper by Sinclair)
increased NAD+/NADH ratio results in Sirtuin activation. (One supplement, Benegene, is marketed to increase this ratio. There are other supplements that may do this.)

Niacinamide is a precursor to NAD+. It looks like if there is too little, the ratio is decreased, but too much, and Sirt1 is deactivated? Blocking the Niacinamide binding sight might make more niacinamide available for conversion to NAD+ ???

Things promise to get very interesting.