The NAD biosynthesis begins with L-tryptophan interacting with oxygen through an indeleoamine 2,3-dioxygenase resulting in the release of N-formylkynurenine. This compound reacts with water through a kynurenine formamidase resulting in the release of formic acid, a hydrogen ion andL-kynurenine. The latter compound reacts with oxygen, hydrogen ion, NADPH through a kynurenine 3-monoxygenase resulting in the release of water, NADP and 3-hydroxy-L-kynurenine. The latter compound reacts with water through a kynureninase resulting in the release of L-alanine, hydrogen ion and 3-hydroxyanthranillic acid. The latter compound reacts with oxygen through a 3-hydroxyanthranilate 3,4-dioxygenase resulting in the release of hydrogen ion and 3-amino-3-carboxymuconic acid semialdehyde. The latter compound then spontaneously releases water and quinolinic acid. Quinolinic acid reacts with PRPP and hydrogen ion through a nicotinate-nucleotide pyrophosphorylase resulting in the release of carbon dioxide, pyrophosphate and nicotinate beta-D-ribonucleotide. Nicotinate beta-D-ribonucleotide can also result from two other set of reactions: a) Nicotinate D-ribonucleoside being phosphorylated through an ATP dependent nicotinamide riboside kinase resulting in the release of ADP, hydrogen ion and nicotinate beta-D-ribonucleotide. b) nicotinamide riboside react with water through uridine nucleosidase resulting in the release of D-Ribose, hydrogen ion and niacinamide. Niacinamide react with water through nicotinamidase resulting in the release of ammonium and nicotinic acid. Nicotinic acid reacts with PRPP , water and ATP through a nicotinate phosphoribosyltransferase resulting in the release of pyrophosphate, ADP, phosphaste and nicotinate beta-D-ribonucleotide. Nicotinate beta-D-ribonucleotide reacts with ATP and hydrogen ion through a nicotinamide/nicotinic acid mononucleotide adenylyltransferase resulting in the release of pyrophosphate and nicotinic acid adenine dinucleotide. The latter compound reacts with glutamine, water, and ATP through a glutamine dependent NAD synthetase resulting in the release of pyrophosphate, AMP, hydrogen ion, glutamic acid and NAD. NAD can also be biosynthesized through a nicotinamide riboside being phosphorylated through an ATP driven nicotinamide riboside kinase resulting in the release of ADP, hydrogen ion and nicotinamide ribotide. The latter compound reacts with ATP and a hydrogen ion through a nicotinamid acid mononucleotide adenylyltransferase resulting in the release of a pyrophosphate and NAD. NAD is degraded through a NAD dependent histone deacetylase resulting in SIR2 resulting in the release of 3-O acetyl ADP-ribose and niacinamide which can be incorporated into the pathway.

NAD Metabolism References