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Review
. 2019 Feb 28;47(1):131-147.
doi: 10.1042/BST20180420. Epub 2018 Dec 17.

The Chemistry of the Vitamin B3 Metabolome

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Free PMC article
Review

The Chemistry of the Vitamin B3 Metabolome

Mikhail V Makarov et al. Biochem Soc Trans. .
Free PMC article

Abstract

The functional cofactors derived from vitamin B3 are nicotinamide adenine dinucleotide (NAD+), its phosphorylated form, nicotinamide adenine dinucleotide phosphate (NADP+) and their reduced forms (NAD(P)H). These cofactors, together referred as the NAD(P)(H) pool, are intimately implicated in all essential bioenergetics, anabolic and catabolic pathways in all forms of life. This pool also contributes to post-translational protein modifications and second messenger generation. Since NAD+ seats at the cross-road between cell metabolism and cell signaling, manipulation of NAD+ bioavailability through vitamin B3 supplementation has become a valuable nutritional and therapeutic avenue. Yet, much remains unexplored regarding vitamin B3 metabolism. The present review highlights the chemical diversity of the vitamin B3-derived anabolites and catabolites of NAD+ and offers a chemical perspective on the approaches adopted to identify, modulate and measure the contribution of various precursors to the NAD(P)(H) pool.

Keywords: chemical biology; metabolome; vitamin B3.

Conflict of interest statement

Competing Interests

The Authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1.
Figure 1.. Precursors to NAD+.
Blue box: PRPP-dependent NAD+ biosynthetic pathways; Green box: PRPP and vitamin B1, B2 and B6-independent pathways; PRPP, 5-phospho-1-pyrophosphoriboside; vitamin B1, thiamine; vitamin B2, riboflavin; vitamin B6, pyridoxine; NA, niacin/nicotinic acid; Nam, niacinamide/nicotinamide; NR, nicotinamide riboside; NAR, nicotinic acid riboside.
Figure 2.
Figure 2.
Synthetic routes to nicotinamide riboside (NR+X).
Figure 3.
Figure 3.
Reduction in derivatives of NR+X into corresponding NRH derivatives.
Figure 4.
Figure 4.
General representation of isotope-labeled NR derivative; illustrative labeled sites are shown by colored asterisks.
Scheme 1.
Scheme 1.. Detailed biosynthetic pathways to the NAD(P)(H) pool components.
trp, tryptophan; Gln, glutamine; PRPP, 5-phosphoriboside pyrophosphate; NAPRT, nicotinic acid phosphoribosyl transferase; NamPRT, nicotinamide phosphoribosyl transferase; NMNAT, nicotinamide mononucleotide adenylyl transferase; NRK, nicotinamide riboside kinase; NADS, nicotinamide adenine dinucleotide synthase; NADK, nicotinamide adenine dinucleotide kinase; NADHK, NADH kinase; NQO2: N-ribosyldihydronicotinamide : quinone reductase 2.
Scheme 2.
Scheme 2.
Synthetic sequence to 1-β-D-ribofuranoside nicotinamide chloride.
Scheme 3.
Scheme 3.
Synthesis of the reduced form of NR as a synthetic intermediate to NR.

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