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The chemistry of the vitamin B3 metabolome.

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.

SUBMITTER: Makarov MV

PROVIDER: S-EPMC6411094 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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The chemistry of the vitamin B3 metabolome.

Makarov Mikhail V MV Trammell Samuel A J SAJ Migaud Marie E ME

Biochemical Society transactions 20181217 1

The functional cofactors derived from vitamin B3 are nicotinamide adenine dinucleotide (NAD<sup>+</sup>), its phosphorylated form, nicotinamide adenine dinucleotide phosphate (NADP<sup>+</sup>) 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 generatio ...[more]

PMID: 30559273

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Project description:BackgroundMetabolic homeostasis is substantially disrupted in critical illness. Given the pleiotropic effects of vitamin D, we hypothesized that metabolic profiles differ between critically ill patients relative to their vitamin D status.MethodsWe performed a metabolomics study on biorepository samples collected from a single academic medical center on 65 adults with systemic inflammatory response syndrome or sepsis treated in a 20-bed medical ICU between 2008 and 2010. To identify key metabolites and metabolic pathways related to vitamin D status in critical illness, we first generated metabolomic data using gas and liquid chromatography mass spectroscopy. We followed this by partial least squares-discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis to identify groups of metabolites and pathways that were differentiates of vitamin D status. Finally we performed logistic regression to construct a network model of chemical-protein target interactions important in vitamin D status.ResultsMetabolomic profiles significantly differed in critically ill patients with 25(OH)D ≤ 15 ng/ml relative to those with levels >15 ng/ml. In particular, increased 1,5-anhydroglucitol, tryptophan betaine, and 3-hydroxyoctanoate as well as decreased 2-arachidonoyl-glycerophosphocholine and N-6-trimethyllysine were strong predictors of 25(OH)D >15 ng/ml. The combination of these five metabolites led to an area under the curve for discrimination for 25(OH)D > 15 ng/ml of 0.82 (95% CI 0.71-0.93). The metabolite pathways related to glutathione metabolism and glutamate metabolism are significantly enriched with regard to vitamin D status.ConclusionVitamin D status is associated with differential metabolic profiles during critical illness. Glutathione and glutamate pathway metabolism, which play principal roles in redox regulation and immunomodulation, respectively, were significantly altered with vitamin D status.

Dataset Information

The chemistry of the vitamin B3 metabolome.

Publications

The chemistry of the vitamin B3 metabolome.

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