Ribose Metabolism main co-factor is NAD+ / Niacinamide...
Several metabolic routes allow NAD+ synthesis from four different precursors (blue box). In the de novo pathway, NAD+ is synthesized from L-tryptophan, which is converted to quinolinic acid (not shown) and then to nicotinic acid mononucleotide (NaMN). An import pathway originates with nicotinic acid (Na), which is converted to NaMN (through the Preiss–Handler pathway), nicotinic acid adenine dinucleotide and then NAD+. A salvage pathway uses nicotinamide (Nam) to regenerate NAD+(Refs
1,
2). Na and Nam are collectively referred to as niacin, or vitamin B3. A fourth, recently discovered route incorporates nicotinamide riboside in the salvage pathway
106. NAD+ and its phosphorylated relative NADP (not shown) are used as cofactors in several different redox reactions that are catalysed by NAD+ dehydrogenases (yellow box). These reactions are not accompanied by any net consumption of the nucleotides. Conversely, a net loss of NAD+ is associated with ADP-ribose-transfer reactions that take place during ADP-ribose cyclization (orange box), mono- or poly(ADP-ribosyl)ation and the deacetylation of proteins (green boxes). All these ADP-ribose-transfer reactions link NAD+ metabolism and the energy status of the cell to various aspects of cellular signalling for different cellular functions. Free ADP-ribose or derivative molecules can result from poly(ADP-ribose) degradation, which is catalysed by PARG isoforms and hydrolases (ARHs; ADP-ribosylarginine hydrolases), or from O-acetyl-ADP-ribose hydrolysis by Nudix O-acetyl-ADP-ribose hydrolase. These molecules might participate in the activation of TRPM2 channels (which are involved in calcium entry)
107 and might react with proteins (resulting in glycation), which can lead to severe endothelial dysfunction, as in the case of diabetes-mellitus-associated atherosclerosis and other cardiovascular diseases.
NaDS, NAD+ synthase; NaMNAT, nicotinic acid mononucleotide adenylyltransferase; Nampt, nicotinamide phosphoribosyl transferase; NaPRTase, nicotinic acid phosphoribosyltranferase; NMNAT, nicotinamide mononucleotide adenylyltransferase; Nrk1, nicotinamide riboside kinase-1; PARG, poly(ADP-ribose) glycohydrolase; PARP, poly(ADP-ribose) polymerase.