CoFactor: Nicotinamide-adenine dinucleotide
NAD(P) assists in hydride transfers . Therefore the cofactor exists in two states: NAD(P)+ and NAD(P)H/H+.
In addition to its catalytic function, NAD(P) is also involved in regulation. NAD levels in the cell influence transcriptional reprogramming and regulate physiological functions of a cell in response to perturbations in NAD(H) levels to maintain homeostatic conditions .
The nicotinamide ring (pyridine ring) is planar in the oxidised form but distorted (boat conformation) in the reduced form . This is not always visible in the PDB structures because some of the reduced NADs have been subjected to a refinement algorithm that uses standard planar restraints on the cofactor .
The double bond between C5 and C6 is weakened upon adduct formation.
The hydride transfer mechanism involving NAD(P) cofactors is accompanied by the transfer of a proton. The coupling between hydride and proton transfer has to be well orchestrated to prevent the hydride ion and proton to form a hydrogen molecule .
NAD is involved in DNA repair, calcium-dependent signalling pathways and lifespan extension in yeast .
NAD is the most abundant electron carrier in cell metabolism .
NAD is an essential cofactor for both energy metabolism and signal transduction .
For some enzymes, NAD is not a coenzyme (dissociating from the protein after each catalytic cycle) but a prosthetic group (that remains bound to the enzyme and does not exchange with external NAD).
Due to the dependency of human cells on the nutritional intake of vitamin B3, the biosynthetic enzymes are antibiotic drug targets ,.