Figure 1





Figure 1 : 

Multiple roles of oxidized nicotinamide adenine dinucleotide (NAD+) in energy metabolism and cell signalling. A. Skeletal formula of NAD+ showing the site of reduction that gives rise to the reduced form (NADH) in oxidoreduction reactions. The boxes indicate the nicotinamide (NAM) and adenosine diphosphate-ribose (ADPR) moieties that are released after cleavage by NAD+-consuming enzymes. B. NAD+ and its vitamin B3 precursors NAM and nicotinamide riboside (NR) can be found in the extracellular compartment. NAD+ synthetic pathways are highlighted in green and consuming pathways are highlighted in red. NAD+ present in food is broken down into nicotinamide mononucleotide (NMN), NAM or NR components. NMN is converted to NR by CD73 5′-ectonucleotidase. NR can enter the cells through nucleoside transporters. The NAD+ biosynthetic pathways are initiated by the nicotinamide phosphoribosyl transferase (Nampt) and nicotinamide riboside kinase (Nmrk) enzymes forming NMN, followed by the nicotinamide mononucleotide adenylyl transferase (Nmnat) enzymes fusing an NMN to an ADP moiety to form NAD+. The NAD+ coenzyme is reduced to NADH during glycolysis, fatty acid β-oxidation (FAO) and mitochondrial oxidative phosphorylation, and is the precursor of oxidized/reduced NAD phosphate (NADP+/NADPH) in the cytosol and mitochondria. NAD+ is cleaved by enzymes, such as sirtuins (SIRT) and poly(ADPR) polymerases (PARP), involved in gene regulation for oxidative stress resistance and mitochondrial biogenesis. NAD is also used by ADP-ribosylases, such as ADP-ribosyl transferase C1 (ART1), located at the membrane. CD38 cleaves NAD+ to generate cyclic ADPR (cADPR) and ADPR second messengers or nicotinic acid adenine dinucleotide phosphate (NAADP) from NADP. The second messengers are involved in calcium (Ca2+) mobilization from the extracellular compartment (Trpm2) and intracellular stores, notably the sarcoplasmic reticulum, through the activation of the ryanodin receptor (RyR) or the lysosomal stores. Ac: acetyl; ATP: adenosine triphosphate; CoA: coenzyme A; ETC: electron transport chain; FoxO: forkhead box O; GSH: glutathione; Idh2: isocitrate dehydrogenase 2; NADK: NAD kinase; Nnt: nicotinamide nucleotide transhydrogenase; NOX: NADPH oxidase; Nrt1: nitrate transporter 1; PGC: peroxisome proliferator-activated receptor gamma coactivator; ROS: reactive oxygen species; Trpm2: transient receptor potential cation channel, subfamily M, member 2; TXN: thioredoxin.