Table 1.
Key Enzymes in the NAD+ Biosynthetic Pathways
| Enzyme | Activity | Pathway(s) |
|---|---|---|
| Quinolinate phosphoribosyl transferase (QPRT) | Catalyzes the formation of nicotinic acid mononucleotide (NAMN) from quinolinic acid (QA)a | De novo pathway |
| NAD+ synthetase (NADS) | Catalyzes the amidation of NAAD, leading to the production of NAD+ | De novo pathway |
| Nicotinic acid phosphoribosyl transferase (NAPRT) | Catalyzes the formation of NAMN from nicotinic acid (NA); rate-limiting step [125] | NA (‘Preiss–Handler’) salvage pathway |
| Nicotinamide phosphoribosyl transferase (NAMPT) | Catalyzes the production of nicotinamide mononucleotide (NMN) from NA; rate-limiting step [126] | NMN salvage pathway |
| Nicotinamide riboside kinase (NMRK) | Catalyzes the production of NMN from NR; rate-limiting step [87,127] | NR pathway |
| Nicotinamide mononucleotide adenylyltransferase (NMNAT) | Catalyzes the formation of nicotinic acid adenine dinucleotide (NAAD) from NAMN, or of NAD+ from NMN | De novo and salvage pathways |
a
The de novo NAD+ synthesis pathway originates with tryptophan, and through the kynurenine (Kyn) pathway converges with dedicated NAD+ synthesis pathways via quinolinic acid (QA). The Kyn pathway also feeds other metabolic pathways. Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) catalyze the first and rate-limiting step of the Kyn pathway. QPRT is positioned to catalyze the rate-limiting step of the specific de novo NAD+ biosynthesis portion of the pathway, but whether it does so is debated in the literature and may be context-specific [125,128–130].