Nicotinic adenine dinucleotide phosphate
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| Surname | Nicotinic adenine dinucleotide phosphate | ||||||||||||||||||
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| Molecular formula | C 21 H 28 N 6 O 18 P 3 | ||||||||||||||||||
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| Molar mass | 745.40 g mol −1 | ||||||||||||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||||||||
Nicotinic adenine dinucleotide phosphate ( NAADP ) is a molecule that plays an important role as a second messenger not only in mammals but in many other multicellular organisms . NAADP is considered one of the most effective natural ingredients for releasing calcium ions.
description
NAADP was discovered in the brain in the early 1990s. This molecule is one of the so-called new second messengers in mammalian cells . In human cells it mediates a very strong release of calcium , although the mechanism and location of its receptor are still unclear. An interaction with the ryanodine receptor of the endoplasmic reticulum is likely .
The release of calcium ions mediated by NAADP occurs independently of inositol trisphosphate and cADP-ribose , two other second messengers .
Synthesis mechanism
NAADP is likely made by an enzyme called ADP-ribosylcyclase , which occurs in various forms in humans. The currently known forms are CD38 and CD157 , two surface proteins that have long been known as antigens on leukocytes (white blood cells). Since 2005 we have also known about the important role of CD38 in chronic lymphocytic leukemia , a type of blood cancer that has so far been difficult to treat. New therapeutic approaches that are supposed to work by blocking the CD38 just mentioned are currently being researched, as fewer side effects could be achieved with a more specific therapeutic approach than before .
Synthesis requirements
It is not entirely established how NAADP is synthesized in vivo .
One possibility to generate NAADP is via a so-called base exchange reaction . NAADP is formed from the precursor molecule nicotinamide adenine dinucleotide phosphate (NADP + ), which is converted to NAADP by a NAP (P )ase in the presence of nicotinic acid .
However, this reaction only takes place at a reduced pH value (<6.8). This prerequisite has so far been a mystery, since only a few organelles of the cell (for example in the lysosomes ) have such acidic environmental conditions. In addition, a higher concentration of nicotinic acid is required for the reaction to proceed than can be present in living cells. Another problem is that the reaction in human cells is believed to be catalyzed by CD38, an ectoenzyme. As a result, NADP + must first be transported out of the cytosol and, after the reaction has ended, NAADP again into the cytosol.
Alternatively, it is speculated whether NAADP can be produced by deamination of NADP + s or by phosphorylation of NAAD + by means of ATP. The latter would be a reaction analogous to the phosphorylation of NAD + , presumably catalyzed by the NADP + kinase.
Individual evidence
- ↑ a b Datasheet Nicotinic acid adenine dinucleotide phosphate sodium salt from Sigma-Aldrich , accessed on April 16, 2011 ( PDF ).
- ^ A b Gerhard Krauss: Biochemistry of Signal Transduction and Regulation. 4th, enlarged and improved edition. Wiley-VCH Verlag, 2008, ISBN 978-3-527-31397-6 , p. 286.
literature
- EN Chini et al: Nicotinate adenine dinucleotide phosphate (NAADP) triggers a specific calcium release system in sea urchin eggs. In: J Biol Chem . 270 (7), 1995, pp. 3216-3223. PMID 7852407 ; PDF (free full text access, in English)
- HC Lee, R. Aarhus: A derivative of NADP mobilizes calcium stores insensitive to inositol trisphosphate and cyclic ADP-ribose. In: J Biol Chem. 270 (5), 1995, pp. 2152-2157. PMID 7836444 ; PDF (free full text access, in English)
- EN Chini, FG De Toledo: Nicotinic acid adenine dinucleotide phosphate: a new intracellular second messenger? In: Am J Physiol Cell Physiol. 282 (6), 2002, pp. C1191-C1198. PMID 11997232 .
- L. Santella: NAADP: a new second messenger comes of age. In: Mol Interv. 5 (2), 2005, pp. 70-72. PMID 15821154 ; PDF (free full text access, in English)
- RA Billington et al .: A transport mechanism for NAADP in a rat basophilic cell line. In: FASEB J . 20 (3), 2006, pp. 521-523. PMID 16403787 PDF (free full text access, in English)
- A. Galione: NAADP, a new intracellular messenger that mobilizes Ca2 + from acidic stores. In: Biochem Soc Trans . 34 (Pt 5), 2006, pp. 922-926. PMID 17052228 ; PDF free full text access, in English)
- N. Pollak et al: The power to reduce: pyridine nucleotides - small molecules with a multitude of functions. In: Biochem J. 402 (2), 2007, pp. 205-218. PMID 17295611 ; PMC 1798440 (free full text, PDF).