Fig. 1: The synthesis and consumption pathways of NAD⁺ in mammals and intestinal flora.

Two main pathways involved in mammalian NAD synthesis: de novo and salvage pathway. The former pathway converts Trp to QA through the kynurenine pathway and synthesizes NAD⁺. The main precursors of NAD⁺ are NAM, NA, NR, and NMN. NAD⁺-consuming enzymes mainly include SIRTs, PARPs, and CD38, and the metabolites after they use up NAD all contain NAM. In the intestinal flora, the de novo synthesis of NAD⁺ mainly depends on Asp rather than Trp. Although different in the de novo pathway, they share the same precursors for NAD⁺ synthesis. Dependence on the same precursors must lead to competition or cooperation in NAD⁺ metabolism between mammals and their microbiota. The synthetic pathway marked by the red line is specific to gut flora. Trp tryptophan, ACMS α-amino-β-carboxymuconate-ε-semialdehyde, QA quinolinic acid, AMS α-amino-β-muconate-ε-semialdehyde, NaAD nicotinic acid adenine dinucleotide, MNAM methylation of NAM, Asp aspartic acid, ImminoAsp immino-aspartate, QPRT nicotinate-nucleotide pyrophosphorylase, NMNAT Nicotinamide/nicotinic acid mononucleotide adenylyltransferase, NADS glutamine-dependent NAD⁺ synthetase, NNMT nicotinamide N-methyltransferase, NRK nicotinamide riboside kinase, NADP nicotinamide adenine dinucleotide phosphate. Figure 1 was created by Adobe Illustrator.