Understanding the Biosynthesis of NAD+

NAD biosynthesis

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Discover More about NAD+ in Metabolism & Aging Process

The last few years have seen rapid increase in interest in NAD+; also known as nicotinamide adenine dinucleotide. This increased interest has been witnessed in numerous fields of biomedical studies, with a view to establishing the role of NAD+ in our bodies. Several recent studies continue to demonstrate the significance biosynthesis of NAD+ for the pathological and physiological processes of aging and age related diseases.

What does it do?

Nicotinamide adenine dinucleotide is an important element in cellular processes that are necessary for supporting a number of metabolic functions. The definitive function of NAD+ is a coenzyme that helps in catalyzing redox reactions in cells, where it is in turn reduced to NADH. This is often witnessed in various fundamental metabolic pathways.

Crucial Precursors and Intermediates to NAD+ Synthesis

There are five main intermediates and precursors to NAD+ synthesis as follows:

Nicotinamide
Nicotinamide Mononucleotide (NMN)
Nicotinamide Riboside (NR)
Trypophan
Nicotinic acid

The NAD+ Biosynthesis

In mammals, the salvage pathway from nicotinamide is the major process for NAD+ biosynthesis. During this process, nicotinamide is changed to nicotinamide mononucleotide, which is an important NAD+ intermediate. Conversion of Nicotinamide to nicotinamide mononucleotide involves nicotinamide phosphoribosyltransferase, abbreviated as NAMPT. This is the enzyme that limits rates in this pathway.

Once nicotinamide has been changed to MNM by NAMPT, a further conversion of NMN into NAD+ takes place by NMNATs. In other words, NAMPT plays an essential role in regulating the levels of NAD+ in cells.

NAD+ & Aging

The popular discussions on NAD+ have now reached a global consensus that nicotinamide adenine dinucleotide reduces at organismal, tissue/organ and cellular levels as one gets older. In other words, NAD+ levels will drop as you start aging. The decline starts in the cells, which make up tissues and organs, hence resulting in the whole body feeling this decline.

The activities of enzymes that consume nicotinamide adenine dinucleotide are affected by the NAD+ decline. This eventually contributes to the broad range of age-related pathophysiologies you are trying to run away from.

Sirtuins are also a family of enzymes that play significant roles in translating the changes of NAD+ to regulating numerous enzymes for metabolism, stress response, DNA repair, circadian rhythm, chromatin remodeling as well as other processes in the cells. In essence, NAD+ and sirtuins are highly interlinked in the regulation of most cellular processes in the body.

NAD+ will significantly decline with aging because the formation of NAD+ through NAMPTs also decreases substantially.