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CoFactor: Nicotinamide-adenine dinucleotide

General information

2D representation

Nicotinamide-adenine dinucleotide

Key facts

Cofactor type    coenzyme or prosthetic group
Human metabolism    from Vitamin B3
IUPAC name    2'-O-phosphonoadenosine 5'-{3-[1-(3-carbamoylpyridinio)-1,4-anhydro-D-ribitol-5-yl] hydrogen diphosphate}
Curator    JDF

Tags

Molecular function

NAD(P) assists in hydride transfers [2]. 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 [3].

Chemical properties

The nicotinamide ring (pyridine ring) is planar in the oxidised form but distorted (boat conformation) in the reduced form [1]. 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 [1].

The double bond between C5 and C6 is weakened upon adduct formation.[2]

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 [1].

Pathways

NAD is involved in DNA repair, calcium-dependent signalling pathways and lifespan extension in yeast [4].

Comment

NAD is the most abundant electron carrier in cell metabolism [2].

NAD is an essential cofactor for both energy metabolism and signal transduction [4].

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)[6].

Due to the dependency of human cells on the nutritional intake of vitamin B3, the biosynthetic enzymes are antibiotic drug targets [5],[4].

References

[1] pubmed:19028476
[2] pubmed:11134046
[3] pubmed:20713194
[4] pubmed:12504674
[5] pubmed:20857400
[6] pubmed:11893060
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