Nicotinic acid adenine dinucleotide phosphate

Nicotinic acid adenine dinucleotide phosphate
Identifiers
CAS number	5502-96-5
PubChem	123953
IUPHAR ligand	2450
Properties
Molecular formula	[C21H28N6O18P3]+
Molar mass	745.398 g/mol
Y acid adenine dinucleotide phosphate (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Nicotinic acid adenine dinucleotide phosphate, also known as NAADP⁺, is a nucleotide very similar to NADP, with the nicotinamide replaced with a niacin molecule. NAADP is one of the most potent Calcium signalling messenger molecules, causing release of calcium from intracellular stores.

Metabolism

Bifunctional ectoenzymes of the CD38 family is believed to synthesize NAADP⁺ from NADP⁺ (by exchange of nicotinamide for niacin under acidic conditions). However whether the so called base exchange reaction is responsible for NAADP generation in vivo, is questionable and remains to be proven. NAADP is believed to be hydrolysed in two selective mechanism. 1. Hydrolysis by CD38 and 2'phosphatase cleavage by a Ca2+ sensitive phosphatase. Theoretically pyrophosphatase also have the capability to hydrolyse NAADP.

Transport

The two paralogous enzymes- transmembrane CD38 and GPI anchored CD157, that produce NAADP (and cADPR) in humans both have their active synthesis site in the ectodomain. Though this may involve vesicular synthesis but it has been shown that it is produced at the extracellular sites, and also can act when produced by a different cell or added artificially from outside. So the NAADP has to enter the cell either by diffusion or by transport. Considering the fact that the substrate of NAADP synthesis (NADP) itself is very sparse in the extracellular medium, a purse diffusion based mechanism has been suspected to be less likely than a transporter mediated path. This is compatible with recent data which indicate a carrier mediated transport partially blockable by dipyridamole and cold temperature.^[1]

Mechanism of action

The real target of NAADP which causes the calcium release is still not clear. There has been some report on a ligand gated calcium release channel present in different distribution compared to both Ryanodine receptors and IP3 receptors. This receptor may be present on both endoplasmic reticulum/nuclear membrane compartments as well as some acidified compartments like lysosome and some secretory vesicles. Some report also suggest that NAADP may act on Ryanodine receptor as well.

A unique feature of NAADP action is its desensitization on prolonged action even when at subthreshold concentration (only in echinoderms like sea urchin). This is supposed to be a part of calcium memory of cellular calcium signaling pathways. In contrast to this mammalian cells display a bell-shaped dependence to NAADP.

See also

• Cyclic ADP-ribose
• IP3

References

1. ^ R. A. Billington, E. A. Bellomo, E. M. Floriddia, J. Erriquez, C. Distasi, and A. A. Genazzani A transport mechanism for NAADP in a rat basophilic cell line The FASEB Journal. 2006;20:521-523. Published online as doi10.1096/fj.05-5058fje [1]

Lee, H.C. and Aarhus, R. (1995) A derivative of NADP mobilizes calcium stores insensitive to inositol trisphosphate and cyclic ADP-ribose. J. Biol. Chem. 270, 2152-2157.