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.
