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. 2016 Aug 18;2:16017. doi: 10.1038/npjamd.2016.17

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Copyright © 2016 Published in partnership with the Japanese Society of Anti-Aging Medicine

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Comparison of NAD⁺ biosynthetic pathways between yeast/invertebrates and mammals. Left panel: NAD⁺ biosynthetic pathways in the budding yeast Saccharomyces cerevisiae and invertebrates. The pathways from NIC, NA, and NR and the de novo pathway from tryptophan are shown. Right panel: NAD⁺ biosynthetic pathways in mammals. In mammals, NIC is a predominant NAD⁺ precursor. NA, NR, and tryptophan can also be utilized to synthesize NAD⁺. The de novo pathway and the NAD⁺ biosynthetic pathway from NA are evolutionarily conserved, whereas the NAD⁺ biosynthetic pathway from NIC is mediated by NAMPT. In this figure, only sirtuins are shown among multiple NAD⁺-consuming enzymes that break NAD⁺ into nicotinamide and ADP-ribose. Mammals have two NR kinases (Nrk1 and 2) and ecto-5′-nucleotidase CD73 to produce NMN and NR, respectively. NA, nicotinic acid; NAD+, nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyltransferase; NIC, nicotinamide; NR, nicotinamide riboside; Nrk1, nicotinamide ribose kinase 1; Npt1, nicotinic acid phosphoribosyltransferase; Nma1, 2, nicotinic acid mononucleotide adenylyltransferase 1, 2; Nnt1, nicotinamide-N-methyltransferase; Npt, nicotinic acid phosphoribosyltransferase; NMNAT, NMN adenylyltransferase; NNMT, nicotinamide-N-methyltransferase; NaMN, nicotinic acid mononucleotide; NMN, nicotinamide mononucleotide; Pho5, 8, phosphatase 5, 8; Pnp1, purine nucleoside phosphorylase; Pnc1, nicotinamidase; Qpt, quinolinic acid phosphoribosyltransferase; Qns1, NAD synthetase; Qpt1, quinolinic acid phosphoribosyltransfease; Urh1, uridine hydrolase.