Nicotinic acid adenine dinucleotide phosphate
- NAADP
- Nicotine - TPN
Attention
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Nicotinsäureadenindinukleotidphosphat ( NAADP ) is a molecule that plays an important role as a second messenger not only to mammals, but also in many other multicellular organisms. NAADP is considered one of the most effective natural active ingredients for the release of calcium ions.
Description
Was discovered NAADP beginning of the 1990s in the brain. This molecule is counted among the so-called new second messengers in cells of mammals. In human cells, it conveys a very strong calcium release, the mechanism and the location of its receptor are still unclear. Is likely to interact with the ryanodine receptor of the endoplasmic reticulum.
The NAADP -mediated release of calcium ions is independent of inositol trisphosphate and cADP - ribose, two other second messenger.
Synthesis mechanism
Produces NAADP probably by an enzyme called ADP- ribosyl cyclase, which is found in various forms in man. The currently known forms of CD38 and CD157, two surface proteins that are already longer than antigens on leukocytes ( white blood cells ) are known. Since 2005, we also know the important role of CD38 in chronic lymphocytic leukemia, a cancer of the blood, which is so far difficult to treat. New therapeutic approaches that are intended to act by blocking the CD38 just mentioned, are currently explored as fewer side effects could be achieved by a more specific approach to therapy than before.
Synthesis conditions
It is not very well known, and NAADP is synthesized in vivo.
An ability to generate NAADP is a so-called base exchange reaction. NAADP thereby formed from the precursor molecule nicotinamide adenine dinucleotide phosphate ( NADP ), which is converted in the presence of nicotinic acid to NAADP by NAP (P) ase.
However, this reaction takes place only at a reduced pH ( < 6.8 ). This condition is so far a mystery, since only a few organelles of the cell ( for example, in the lysosomes ) prevail such acidic environments. Moreover, a higher concentration of nicotinic acid for the reaction to occur is required, as may be present in living cells. Another problem is that the response in human cells is likely to CD38, an ectoenzyme catalyzed. It follows that it first NADP from the cytosol, and are transported into the cytosol after expiry of the reaction NAADP again.
Alternatively, it is speculated whether NAADP can be generated by deamination of NADP s or by phosphorylation of NAAD by ATP. The latter would be a similar reaction as the phosphorylation of NAD , presumably catalyzed by the NADP - kinase.