General Background Nicotinamide adenine dinucleotide (NAD) and its phosphorylated derivative, nicotinamide adenine dinucleotidephosphate (NADP) are two of the most important coenzymes in redox reactions in the cell. Generally, NAD is involved in catabolic reactions, while NADP is involved in anabolic reactions. Due to the positive charge on the nitrogen atom in the nicotinamide ring, the oxidized forms of these compounds are often depicted as NAD+ and NADP+, respectively . Most oxidative reactions in cells are accomplished by the removal of hydrogen atoms. In reactions where : NAD or : NADP participate, two hydrogen atoms are typically removed from the substrate. During the reduction of NAD+ (or NADP+) the molecule acquires two electrons and one proton, while the second proton is released into the medium. Thus a typical reaction involving NAD is in the form: NAD+ + 2H -> NADH + H+ NAD+ also has myriad nonredox roles in the cell. It is a substrate in posttranslational covalent modifications of key proteins, such as mono- and poly-ADP ribosylation reactions. NAD+ homeostasis is related to the production of reactive oxygen species responsible for irreversible cellular damage in a number of diseases . It also plays a role in longevity and transcriptional silencing through the regulation of : HS01870, the human homolog of the S. cerevisiae SIR2 protein known to be involved in cell aging and response to DNA damage. SIRT1 is an NAD-dependent p53 deacetylase that binds and deacetylates the p53 protein . NAD+ is synthesised via two major pathways in humans; the : NADSYN-PWY and : NAD-BIOSYNTHESIS-III pathways. About This Pathway In eukaryotes, the de novo pathway starts with : TRP. The role of tryptophan as a precursor for eukaryotic NAD biosynthesis was first suggested by nutritional studies in which humans stricken with pellagra, a nicotinamide (niacin) deficiency disease, recovered after the addition of tryptophan or niacin to their diets . Other studies established tryptophan as a precursor of NAD in many animal and plant systems . In the first and rate limiting step, : TRP is oxidatively cleaved to : N-FORMYLKYNURENINE by the action of one of three enzymes, : CPLX66-442, : HS05502-MONOMER or : MONOMER66-34407, depending upon the tissue. Thus this pathway also describes : TRP degradation, see : TRYPTOPHAN-DEGRADATION-1. In humans, the de novo pathway consists of eight enzymatic steps and one non-enzymatic reaction. At the step catalyzed by the nicotinamide mononucleotide adenylyltransferases, the : NADSYN-PWY and : NAD-BIOSYNTHESIS-III pathways converge

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