Fig. 1.

Cellular functions of NAD⁺. (A) A schematic representation of the NAD⁺ synthetic pathways. NAD⁺ is synthesized from tryptophan via the de novo pathway, nicotinic acid via the Preuss-Handler pathway, or nicotinamide and ADP-ribose via the salvage pathway. Abbreviated metabolites and enzymes are as follows. L-Kyn: l-kynurenine, 3-HK: 3-hydroxykynurenine, 3-HAA: 3-hydroxyanthranilic acid, ACMS: 2-amino-3-carboxymuconic semialdehyde, NAMN: nicotinic acid mononucleotide, NAAD: nicotinic acid adenine dinucleotide, NMN: nicotinamide mononucleotide, NR: nicotinamide ribose, NA: nicotinic acid, R5P: ribose 5 phosphate, PRPP: 5-phosphoribosyl-1-pyrophosphate, TDO: tryptophan 2,3-dioxygenase, AFMID: arylformamidase, KMO: Kynurenine 3-monooxygenase, KYNU: Kynureinase, HAAO: 3-hydroxyanthranilate 3,4-dioxygenase, Qprt: quinolinate phosphoribosyl transferase, Naprt: nicotinate phosphoribosyltransferase, Nmnat: nicotinamide nucleotide adenylyltransferase, NADS: NAD⁺ synthase, Nampt: nicotinamide phosphoribosyltransferase, Parp: poly ADP ribose polymerase, Arpp: ADP-ribose pyrophosphatase, Rppk: ribose phosphate pyrophosphokinase and NRK: nicotinamide ribose kinase. (B) Cell protective and adaptive effects of NAD⁺. NAD(H) functions as an electron carrier that contributes to metabolic processes, including mitochondrial energy metabolism. NAD⁺ also functions as a co-substrate of NAD⁺-consuming enzymes, including sirtuins and Parps. Sirtuins mediate beneficial effects of NAD⁺ in aging and disease conditions. Although NAD⁺ is a precursor of NADP, which plays an essential role in cellular redox homeostasis and metabolic processes, the extent to which NADK-induced NADP production contributes to the salutary effects of NAD⁺ is not fully understood.