Nicotinic acid adenine dinucleotide phosphate
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| Nicotinic acid adenine dinucleotide phosphate | |
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| Molecular formula | [C21H28N6O18P3]+ |
| Molar mass | 745.398 g/mol |
| CAS number | [] |
| PubChem | |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references |
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Nicotinic acid adenine dinucleotide phosphate popularly known as NAADP+ is a nucleotide very similar to NADP differeing only in that instead of the nicotinamide there is a niacin moiety. But this small change makes a lot of difference in their cellular function. NAADP is one of the most potent Calcium signaling messenger causing release of calcium from intracellular stores.
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[edit] Metabolism
Bifunctional ectoenzymes of the CD38 family synthesize NAADP+ from NADP+ (by exchange of nicotinamide for niacin under acidic conditions) and the same enzymes are also capable to hydrolyzing them.
[edit] 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]
[edit] 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.
An unique feature of NAADP action is its desensitization on prolonged action even when at subthreshold concentration. This is supposed to be a part of calcium memory of cellular calcium signaling pathways.
[edit] Also see
[edit] references
- ^ 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]
Second messengers: IP3 | NAADP | cADPR
Intracellular calcium store gates: IP3 receptor | Ryanodine receptor | putative NAADP receptor
Calcium pumps and exchangers: SERCA | Na/Ca antiport | Ca/H antiport
calcium binding protein domains: EF hand domain |C2 domain
Calcium based molecular switches, and kinases: troponin c | CaM | CaM kinases | PKC | NCS
Intracellular Calcium chelators (calcium buffers) and calcium sensors: Calbindin | S100 | pervalbumin | Calretinin | Calsequestrin | Sarcalumenin | Phospholamban | Synaptotagmins
Calcium dependent proteases: Calpain
Calcium dependent cytoskeleton remodeling proteins: Gelsolin
Cell membrane calcium channels: VDCC | TRP | NMDA receptor | AMPA receptor | 5-HT3 receptor | P2X Receptor
Calcium regulated chaperones: calreticulin | calnexin
Calcium based adhesion molecules: cadherin
parathormone | Calcitonin | calcium receptor | vitamin D
