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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on December 28, 2007; DOI: 10.1124/jpet.107.120758

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Received for publication June 14, 2007.
Revised December 21, 2007.
Accepted for publication December 27, 2007.

NAD+ and Vitamin B3: From metabolism to therapies

Anthony A. Sauve 1*

1 Weill Medical College Cornell University

* Address correspondence to: E-mail: aas2004{at}med.cornell.edu

Abstract

The role of NAD+ metabolism in health and disease is of increased interest as the use of niacin (nicotinic acid) has emerged as a major therapy for treatment of hyperlipidemias and with the recognition that nicotinamide can protect tissues and NAD+ metabolism in a variety of disease states including ischemia/reperfusion. In addition, a growing body of evidence supports the view that NAD+ metabolism regulates important biological effects including lifespan. NAD+ exerts potent effects through the poly-ADP-ribosyl polymerases (PARPs), mono-ADP-ribosyltransferases (ARTs) and the recently characterized sirtuin enzymes. These enzymes catalyze protein modifications such as ADP-ribosylation and deacetylation, leading to changes in protein function. These enzymes regulate apoptosis, DNA repair, stress resistance, metabolism and endocrine signaling suggesting that these enzymes and/or NAD+ metabolism could be targeted for therapeutic benefit. This review considers current knowledge of NAD+ metabolism in humans and microbes, including new insights into mechanisms that regulate NAD+ biosynthetic pathways, current use of nicotinamide and nicotinic acid as pharmacological agents and opportunities for drug design that are directed at modulation of NAD+ biosynthesis for treatment of human disorders and infections.


Key words: NAD, metabolism, nicotinamide, nicotinic acid, sirtuins, vitamin


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