Figure 1.

The de novo pathway for the semi-vitamin nicotinamide is also the immune tolerance pathway, and is closely connected to serotonin synthesis and social signaling. This may be a homeostatic circuit that supports energy and nicotinamide/tryptophan acquisition, and responsive internal solutions such as autophagy and symbionts that supply nicotinamide and NAD(H), or, pseudo-symbionts such as cancer that sink nicotinamide excesses, as do metabolic and inflammatory syndromes, but they lead to longer term toxicity.

Abbreviations: SIRTs, sirtuins; PARPs, poly(ADP ribose polymerase); cADP, cyclic adenosine diphosphate; ARTs, T-cell ADP ribosyl-transferase; NNMT, nicotinamide-N-methyl-transferase.