06/20/2016 - RGD publishes three interactive pathway diagram pages for nicotinamide adenine dinucleotide biosynthesis, utilization and metabolism

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme of enzyme-catalyzed reduction-oxidation (redox) reactions. NAD+ and its reduced form NADH, and the phosphorylated NADP/NADPH forms, serve as hydride acceptors or donors in over 2,000 redox reactions. In addition to its known role as a cofactor in redox reactions, NAD+ serves as a substrate for several classes of enzymes that include the sirtuin deacetylases, the adenosine diphosphate (ADP)-ribose transferases/poly(ADP-ribose) polymerases, and the cyclic ADP-ribose (cADPR) synthases, in three distinct utilization pathways. The ensuing protein modification and messenger generation play a spectrum of roles in gene regulatory, signaling, metabolic and cellular homeostasis pathways, and also in aging and diseases. Unlike the reversible shuttling between oxidized and reduced forms, which does not change overall coenzyme concentration, the activity of NAD-consuming enzymes requires the replenishing of the NAD pool. This heightens the importance of NAD biosynthesis and of its regulation. Several routes exist to synthesize NAD from various dietary sources.
Nicotinamide adenine dinucleotide biosynthetic pathway

Nicotinamide adenine dinucleotide utilization pathway

Nicotinamide adenine dinucleotide metabolic pathway

NAD can be synthesized de novo, downstream of kynurenine metabolism or tryptophan degradation, or via several salvage pathways. Click here to investigate this important aspect of NAD metabolism. In addition to its known role as a cofactor in redox reactions, NAD serves as a substrate for several classes of enzymes. There are three pathways of NAD utilization: the sirtuin-mediated pathway and the ADP ribosylation pathways: mono and poly-ribosylation, and cyclic ribosylation. Click here to explore the details. NAD+ and its reduced form NADH, and the phosphorylated NADP/NADPH forms, serve as hydride acceptors or donors in over 2,000 redox reactions. In addition, NAD+ serves as a substrate for several classes of enzymes. There are several ways to form NADP and NADPH and interconvert between the various forms of NAD. Click here to see an overview of NAD metabolism.