Author: Gianpiero Pescarmona
Redox mechanisms in hepatic chronic wound healing and fibrogenesis 2008 PDF
Enzymology of mammalian NAD metabolism in health and disease 2008
Therapeutic potential of SIRT1 and NAMPT-mediated NAD biosynthesis in type 2 diabetes 2009
NAD has various essential roles in metabolism:
1. Cofactor in redox reactions
2. Donor of ADP-ribose moieties in ADP-ribosylation reactions
3. Precursor of the second messenger molecule cyclic ADP-ribose
4. As Adenine Dinucleotide, it has important extracellular roles (Release of beta-nicotinamide adenine dinucleotide upon stimulation of postganglionic nerve terminals in blood vessels and urinary bladder, 2004)
These roles are involved in energy metabolism, mitochondrial functions, calcium homeostasis, generation of oxidative stress, gene expression, immunological functions, aging, and cell death (NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences, 2008).
NAD is also related to bone marrow's health and cancer progression (Niacin deficiency decreases bone marrow poly(ADP-ribose) and the latency of ethylnitrosourea-induced carcinogenesis in rats, 2002), and has a benefical role in preventing neurological degeneration (Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition, 2008).
NAD and Niacin deficiency induce the enzyme Nicotinamide-N-Methyltransferase. High activity of this enzyme is related to Parkinson's Disease and cancer (Nicotinamide, NAD(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra).
NAD, and mostly NAM (Nicotinamide), have a particular role in regulation of mesenchimal stem cells. NAM is converted in NAD by the enzyme Nicotinamide phosphoribosyltransferase (Nampt). The activity of this enzyme determines the NAD/NAM ratio.
A good NAD supply increases bone mineralization and stimulates osteocyte proliferation.
A bad NAD supply, represented by an high concentration of NAM, induces adipocyte proliferation and blocks osteocyte growth, potentially leading to osteoporosis (Nicotinamide phosphoribosyltransferase (Nampt) affects the lineage fate determination of mesenchymal stem cells: a possible cause for reduced osteogenesis and increased adipogenesis in older individuals, 2011)
A NAD deficiency can then cause:
1. Deceleration of glycoliosis, Kreb's cycle and most of all electron transport chain
2. An increased susceptibility to ROS damage
3. Bone marrow and brain sufference
4. An increased adipocyte proliferation
5. An increased risk of osteoporosis
NADP has various roles in metabolism:
1. Coenzyme in anabolic reactions
2. Regenerator of reduced glutathione (GSH)
3. Source of reducing equivalents for Cytocrome P450 hydroxilations
NADP deficiency leads to higher sensibility to oxydative damage (NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences, 2008), and higher sensibility to the toxic substrates of Cytocrome P450 (about 75% of drugs, ethanol).
Use of proton pump inhibitors related to vitamin B3 deficiency