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. 2019 Feb 19;60(4):741–746. doi: 10.1194/jlr.S092007

Fig. 2.

Fig. 2.

Pathways modulating NAD+ levels in mammals. NAD+ can be synthesized either via salvage pathways from precursors such as niacin (nicotinic acid), nicotinamide (NAM), and nicotinamide riboside (NR) or de novo from tryptophan (Trp). In the first step of the Preiss-Handler pathway, niacin is converted into NA mononucleotide (NAMN) by nicotinate phosphoribosyltransferase (NAPRT). NAM mononucleotide adenylyltransferase (NMNAT) uses NAMN to generate NA adenine dinucleotide (NAAD), which gets converted into NAD+ by NAD synthetase (NADS). NAD+ synthesis from NAM and NR comprises their conversion into NAM mononucleotide (NMN) by NAM phosphoribosyltransferase (NAMPT) and NAM riboside kinase (NRK), respectively, and the subsequent conversion of NMN into NAD+ by NMNAT. NMN can also be recycled back into NR by CD73. The de novo NAD+ synthesis pathway from Trp consists of eight steps and merges with the Preiss-Handler pathway. Pathways that reduce NAD+ availability include the conversion of NAM into methylnicotinamide (MNA) by N-methyltransferase (NNMT) and NAD+ consumption by enzymes including the sirtuins, CD38, and PARP1.