Signalling Functions of Pyridine Nucleotides

The transfer of the ADP-ribose moiety from NAD onto a biological macromolecule (in almost all cases an amino acid side chain of a protein) is referred to as ADP-ribosylation. Subsequently, another ADP-ribose unit can be attached to the protein-bound ADP-ribose. Further elongation of the ADP-ribose chain will result in poly-ADP-ribosylation. This process will not be further addressed in this chapter. However, mono-ADP-ribosylation, i.e., attachment of a single ADP-ribose unit to a protein, has also been established as a specific protein modification with important r ulatory functions. 

In mammalians, mono-ADP-ribosylation appears to take place primarily on the surface of immune cells. The corresponding transferases are either anchored in the plasma membrane via glycosylphosphatidylinositol (GPI) or secreted. For example, in the lung, the antimicrobial function of a-defensin-1, which is secreted by immune cells, is diminished by mono-ADP-ribosylation.  

Calcium-Mobilising Derivatives ofNAD(P) Cyclic ADP-Ribose andNAADP 

Importandy, the cydic products and NAADP (Fig. 1B) have been established as highly potent intracellular calcium-mobilising agents. Their role for the regulation of fundamental cellular processes, via activation of intracellular calcium stores, has been demonstrated in a variety of model systems (reviewed in refs. 11,13-15). It is interesting to note that the calcium 

Only very recendy, it was discovered that a class of histone deacetylases, the simiins, is dependent on NAD. Sirtuins deacetylate proteins and concomitantly cleave NAD The reaction mechanism appears to be unique for ADP-ribosyl transfers.  

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