Abstract
NAD plays a major role in all cells as substrate for signal transduction and as cofactor in metabolic redox reactions. Since NAD-dependent signaling involves degradation of the nucleotide, continuous restoration of cellular NAD pools is essential. Moreover, NAD-dependent signaling reactions, which include ADP-ribosylation, protein deacetylation by sirtuins and calcium messenger synthesis, are regulated by NAD availability. Consequently, perturbations of NAD supply can have severe consequences and, in fact, have been associated with major human diseases such as age- and dietinduced disorders, neurodegenerative diseases and cancer. Given the increasing awareness of the biological roles of NAD, the routes, molecular mechanisms and regulation of NAD biosynthesis have been the subject of intense research over the last decade. Impressive progress has been made regarding the molecular identification, functional and structural characterization as well as regulation of the human NAD biosynthetic enzymes. Exciting therapeutic concepts have emerged, which aim at modulation of NAD availability by interfering with the biosynthetic network to prevent, reduce or reverse pathological conditions. Since there are several entry points into NAD synthesis, including the known vitamin B3 precursors nicotinamide and nicotinic acid, targeted nutritional supplementation is likely to have beneficial effects in various diseases. On the other hand, inhibition of NAD synthesis promotes cell death and has emerged as a therapeutic concept for cancer treatment.
Keywords: Cancer, compartmentation, metabolism, niacin, signaling, sirtuins, vitamin B3.
Current Topics in Medicinal Chemistry
Title:NAD Biosynthesis in Humans - Enzymes, Metabolites and Therapeutic Aspects
Volume: 13 Issue: 23
Author(s): Christian Dölle, Renate Hvidsten Skoge, Magali R. VanLinden and Mathias Ziegler
Affiliation:
Keywords: Cancer, compartmentation, metabolism, niacin, signaling, sirtuins, vitamin B3.
Abstract: NAD plays a major role in all cells as substrate for signal transduction and as cofactor in metabolic redox reactions. Since NAD-dependent signaling involves degradation of the nucleotide, continuous restoration of cellular NAD pools is essential. Moreover, NAD-dependent signaling reactions, which include ADP-ribosylation, protein deacetylation by sirtuins and calcium messenger synthesis, are regulated by NAD availability. Consequently, perturbations of NAD supply can have severe consequences and, in fact, have been associated with major human diseases such as age- and dietinduced disorders, neurodegenerative diseases and cancer. Given the increasing awareness of the biological roles of NAD, the routes, molecular mechanisms and regulation of NAD biosynthesis have been the subject of intense research over the last decade. Impressive progress has been made regarding the molecular identification, functional and structural characterization as well as regulation of the human NAD biosynthetic enzymes. Exciting therapeutic concepts have emerged, which aim at modulation of NAD availability by interfering with the biosynthetic network to prevent, reduce or reverse pathological conditions. Since there are several entry points into NAD synthesis, including the known vitamin B3 precursors nicotinamide and nicotinic acid, targeted nutritional supplementation is likely to have beneficial effects in various diseases. On the other hand, inhibition of NAD synthesis promotes cell death and has emerged as a therapeutic concept for cancer treatment.
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Cite this article as:
Dölle Christian, Skoge Hvidsten Renate, VanLinden R. Magali and Ziegler Mathias, NAD Biosynthesis in Humans - Enzymes, Metabolites and Therapeutic Aspects, Current Topics in Medicinal Chemistry 2013; 13 (23) . https://dx.doi.org/10.2174/15680266113136660206
DOI https://dx.doi.org/10.2174/15680266113136660206 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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