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Advances in Food and Nutrition Research 2018Nicotinic acid and nicotinamide, collectively referred to as niacin, are nutritional precursors of the bioactive molecules nicotinamide adenine dinucleotide (NAD) and...
Nicotinic acid and nicotinamide, collectively referred to as niacin, are nutritional precursors of the bioactive molecules nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). NAD and NADP are important cofactors for most cellular redox reactions, and as such are essential to maintain cellular metabolism and respiration. NAD also serves as a cosubstrate for a large number of ADP-ribosylation enzymes with varied functions. Among the NAD-consuming enzymes identified to date are important genetic and epigenetic regulators, e.g., poly(ADP-ribose)polymerases and sirtuins. There is rapidly growing knowledge of the close connection between dietary niacin intake, NAD(P) availability, and the activity of NAD(P)-dependent epigenetic regulator enzymes. It points to an exciting role of dietary niacin intake as a central regulator of physiological processes, e.g., maintenance of genetic stability, and of epigenetic control mechanisms modulating metabolism and aging. Insight into the role of niacin and various NAD-related diseases ranging from cancer, aging, and metabolic diseases to cardiovascular problems has shifted our view of niacin as a vitamin to current views that explore its potential as a therapeutic.
Topics: Aging; Humans; Neoplasms; Niacin; Pellagra; Risk Factors; Vitamins
PubMed: 29477227
DOI: 10.1016/bs.afnr.2017.11.003 -
Frontiers in Molecular Biosciences 2022Tryptophan is an essential amino acid, which is not only a building block for protein synthesis, but also a precursor for the biosynthesis of co-enzymes and... (Review)
Review
Tryptophan is an essential amino acid, which is not only a building block for protein synthesis, but also a precursor for the biosynthesis of co-enzymes and neuromodulators, such as NAD/NADP(H), kynurenic acid, melatonin and serotonin. It also plays a role in immune homeostasis, as local tryptophan catabolism impairs T-lymphocyte mediated immunity. Therefore, tryptophan plasmatic concentration needs to be stable, in spite of large variations in dietary supply. Here, we review the main checkpoints accounting for tryptophan homeostasis, including absorption, transport, metabolism and elimination, and we discuss the physiopathology of disorders associated with their dysfunction. Tryptophan is catabolized along the kynurenine pathway through the action of two enzymes that mediate the first and rate-limiting step of the pathway: indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). While IDO1 expression is restricted to peripheral sites of immune modulation, TDO is massively expressed in the liver and accounts for 90% of tryptophan catabolism. Recent data indicated that the stability of the TDO protein is regulated by tryptophan and that this regulation allows a tight control of tryptophanemia. TDO is stabilized when tryptophan is abundant in the plasma, resulting in rapid degradation of dietary tryptophan. In contrast, when tryptophan is scarce, TDO is degraded by the proteasome to avoid excessive tryptophan catabolism. This is triggered by the unmasking of a degron in a non-catalytic tryptophan-binding site, resulting in TDO ubiquitination by E3 ligase SKP1-CUL1-F-box. Deficiency in TDO or in the hepatic aromatic transporter SLC16A10 leads to severe hypertryptophanemia, which can disturb immune and neurological homeostasis.
PubMed: 36188218
DOI: 10.3389/fmolb.2022.897929 -
The New England Journal of Medicine Mar 2022
Topics: Diarrhea; Exanthema; Female; Humans; Middle Aged; Neck; Pellagra; Skin
PubMed: 35263522
DOI: 10.1056/NEJMicm2114098 -
JAMA May 2020
Topics: Diet; History, 20th Century; Humans; Malnutrition; Pellagra
PubMed: 32453356
DOI: 10.1001/jama.2019.13455 -
JAMA Feb 2024
Topics: Humans; Pellagra; Medicine in the Arts; Portraits as Topic; History, 20th Century; Paintings
PubMed: 38214915
DOI: 10.1001/jama.2023.27716 -
The Journal of Emergency Medicine Feb 2018
Topics: Alcoholism; Diarrhea; Exudates and Transudates; HIV Infections; Ill-Housed Persons; Humans; Male; Middle Aged; Nausea; Niacin; Nutrition Assessment; Pellagra
PubMed: 29174751
DOI: 10.1016/j.jemermed.2017.10.010 -
Mayo Clinic Proceedings Mar 2022
Topics: Humans; Pellagra
PubMed: 35246285
DOI: 10.1016/j.mayocp.2021.12.007