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{{Distinguish|text=] (NAD{{+}}/NADH)}} |
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{{Refimprove|dateDecember 2009|date=August 2011}} |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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{{Chembox |
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{{Chembox |
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| Verifiedfields = changed |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 400835603 |
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| verifiedrevid = 456480844 |
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| ImageFile = NADP+ phys.svg |
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| ImageFile = NADP+ phys.svg |
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| ImageSize = 200px |
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| ImageSize = |
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| IUPACName = |
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| IUPACName = |
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| OtherNames = |
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| OtherNames = |
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| Section1 = {{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 5674 |
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| ChemSpiderID = 5674 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = <!-- blanked - oldvalue: 213053 --> |
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| ChEMBL = 2364573 |
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| InChI = 1/C21H28N7O17P3/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(44-46(33,34)35)14(30)11(43-21)6-41-48(38,39)45-47(36,37)40-5-10-13(29)15(31)20(42-10)27-3-1-2-9(4-27)18(23)32/h1-4,7-8,10-11,13-16,20-21,29-31H,5-6H2,(H7-,22,23,24,25,32,33,34,35,36,37,38,39)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1 |
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| InChI = 1/C21H28N7O17P3/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(44-46(33,34)35)14(30)11(43-21)6-41-48(38,39)45-47(36,37)40-5-10-13(29)15(31)20(42-10)27-3-1-2-9(4-27)18(23)32/h1-4,7-8,10-11,13-16,20-21,29-31H,5-6H2,(H7-,22,23,24,25,32,33,34,35,36,37,38,39)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1 |
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| InChIKey = XJLXINKUBYWONI-NNYOXOHSBN |
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| InChIKey = XJLXINKUBYWONI-NNYOXOHSBN |
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| StdInChIKey = XJLXINKUBYWONI-NNYOXOHSSA-N |
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| StdInChIKey = XJLXINKUBYWONI-NNYOXOHSSA-N |
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| CASNo = 53-59-8 |
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| CASNo = 53-59-8 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| PubChem = 5885 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| UNII = BY8P107XEP |
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| PubChem = 5885 |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 44409 |
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| ChEBI = 44409 |
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| SMILES = O=C(N)c1ccc(c1)2O((O)2O)COP()(=O)OP(=O)(O)OC5O(n4cnc3c(ncnc34)N)(OP(=O)(O)O)5O |
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| SMILES = O=C(N)c1ccc(c1)2(O)(O)(O2)COP()(=O)OP(=O)(O)OC3O(n4cnc5c4ncnc5N)(3O)OP(=O)(O)O |
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| MeSHName = NADP |
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| MeSHName = NADP |
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}} |
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| Section2 = {{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=21 | H=29 | N=7 | O=17 | P=3 |
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| Formula = C<sub>21</sub>H<sub>29</sub>N<sub>7</sub>O<sub>17</sub>P<sub>3</sub> |
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| Appearance = |
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| MolarMass = 744.413 |
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}} |
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| Section3 = {{Chembox Hazards |
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|Section3={{Chembox Hazards |
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| Solubility = |
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}} |
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'''Nicotinamide adenine dinucleotide phosphate''', abbreviated '''NADP{{+}}''' or '''TPN''' in older notation (triphosphopyridine nucleotide), is a ] used in ]s, such as ] and ] synthesis, which require NADPH as a ]. |
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'''Nicotinamide adenine dinucleotide phosphate''', abbreviated '''NADP'''<ref>{{Cite web | work = PubChem |title=NADP nicotinamide-adenine-dinucleotide phosphate |url=https://pubchem.ncbi.nlm.nih.gov/compound/NADP-nicotinamide-adenine-dinucleotide-phosphate |access-date=2024-08-22 | publisher = U.S. National Library of Medicine |language=en}}</ref><ref>{{Cite book | vauthors = Karlson P |url=https://books.google.com/books?id=lGyeBQAAQBAJ&dq=Nicotinamide+adenine+dinucleotide+phosphate+abbreviated+NADP&pg=PA95 |title=Introduction to Modern Biochemistry |date=2014-05-12 |publisher=Academic Press |isbn=978-1-4832-6778-4 |language=en}}</ref> or, in older notation, '''TPN''' (triphosphopyridine nucleotide), is a ] used in ]s, such as the ] and ] and ] syntheses, which require '''NADPH''' as a ] ('hydrogen source'). NADPH is the ] form, whereas NADP{{+}} is the ] form. NADP{{+}} is used by all forms of cellular life. NADP{{+}} is essential for life because it is needed for cellular respiration.<ref name="pmid26284036">{{cite journal | vauthors = Spaans SK, Weusthuis RA, van der Oost J, Kengen SW | title = NADPH-generating systems in bacteria and archaea | journal = Frontiers in Microbiology | volume = 6 | pages = 742 | date = 2015 | pmid = 26284036 | pmc = 4518329 | doi = 10.3389/fmicb.2015.00742 | doi-access = free }}</ref> |
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NADPH is the ] form of NADP{{+}}. NADP{{+}} differs from ] in the presence of an additional ] on the 2' position of the ] ring that carries the ] ]. |
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NADP{{+}} differs from ] by the presence of an additional ] on the 2' position of the ] ring that carries the ] ]. This extra phosphate is added by ] and removed by NADP<sup>+</sup> phosphatase.<ref>{{cite journal | vauthors = Kawai S, Murata K | title = Structure and function of NAD kinase and NADP phosphatase: key enzymes that regulate the intracellular balance of NAD(H) and NADP(H) | journal = Bioscience, Biotechnology, and Biochemistry | volume = 72 | issue = 4 | pages = 919–930 | date = April 2008 | pmid = 18391451 | doi = 10.1271/bbb.70738 | doi-access = free }}</ref> |
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==In plants== |
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In ], NADP<sup>−</sup> is added by ] in the last step of the electron chain of the ]s of ]. The NADPH produced is then used as reducing power for the biosynthetic reactions in the ] of photosynthesis. In its energized state, it is NADPH, now holding an extra electron. It is used primarily to create the proton gradient in chloroplasts during the light-dependent reactions. |
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==In animals== |
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== Biosynthesis == |
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The oxidative phase of the ] is the major source of NADPH in cells, producing approximately 60% of the NADPH required. |
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=== NADP{{+}} === |
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NADPH provides the reducing equivalents for biosynthetic reactions and the ] involved in protecting against the toxicity of ROS (]), allowing the regeneration of ] (reduced glutathione). |
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In general, NADP<sup>+</sup> is synthesized before NADPH is. Such a reaction usually starts with ] from either the de-novo or the salvage pathway, with ] adding the extra phosphate group. ] allows for synthesis from ] in the salvage pathway, and NADP<sup>+</sup> phosphatase can convert NADPH back to NADH to maintain a balance.<ref name="pmid26284036"/> Some forms of the NAD<sup>+</sup> kinase, notably the one in mitochondria, can also accept NADH to turn it directly into NADPH.<ref>{{cite journal | vauthors = Iwahashi Y, Hitoshio A, Tajima N, Nakamura T | title = Characterization of NADH kinase from Saccharomyces cerevisiae | journal = Journal of Biochemistry | volume = 105 | issue = 4 | pages = 588–593 | date = April 1989 | pmid = 2547755 | doi = 10.1093/oxfordjournals.jbchem.a122709 }}</ref><ref>{{cite journal | vauthors = Iwahashi Y, Nakamura T | title = Localization of the NADH kinase in the inner membrane of yeast mitochondria | journal = Journal of Biochemistry | volume = 105 | issue = 6 | pages = 916–921 | date = June 1989 | pmid = 2549021 | doi = 10.1093/oxfordjournals.jbchem.a122779 }}</ref> The prokaryotic pathway is less well understood, but with all the similar proteins the process should work in a similar way.<ref name="pmid26284036"/> |
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NADPH is also used for ] pathways, such as lipid synthesis, ], and ]. |
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=== NADPH === |
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The NADPH system is also responsible for generating free radicals in immune cells. These radicals are used to destroy pathogens in a process termed the ].<ref>{{cite journal|pmid=18950479}}</ref> |
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NADPH is produced from NADP<sup>+</sup>. The major source of NADPH in animals and other non-photosynthetic organisms is the ], by ] (G6PDH) in the first step. The pentose phosphate pathway also produces pentose, another important part of NAD(P)H, from glucose. Some bacteria also use G6PDH for the ], but NADPH production remains the same.<ref name="pmid26284036"/> |
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], present in all domains of life, is a major source of NADPH in photosynthetic organisms including plants and cyanobacteria. It appears in the last step of the electron chain of the ] of ]. It is used as reducing power for the biosynthetic reactions in the ] to assimilate carbon dioxide and help turn the carbon dioxide into glucose. It has functions in accepting electrons in other non-photosynthetic pathways as well: it is needed in the reduction of nitrate into ammonia for plant assimilation in ] and in the production of oils.<ref name="pmid26284036"/> |
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It is the source of reducing equivalents for ] ] of ], ]s, ]s, and ]s. |
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There are several other lesser-known mechanisms of generating NADPH, all of which depend on the presence of ] in eukaryotes. The key enzymes in these carbon-metabolism-related processes are NADP-linked isoforms of ], ] (IDH), and ]. In these reactions, NADP<sup>+</sup> acts like NAD<sup>+</sup> in other enzymes as an oxidizing agent.<ref>{{cite journal | vauthors = Hanukoglu I, Rapoport R | title = Routes and regulation of NADPH production in steroidogenic mitochondria | journal = Endocrine Research | volume = 21 | issue = 1–2 | pages = 231–241 | date = Feb–May 1995 | pmid = 7588385 | doi = 10.3109/07435809509030439 }}</ref> The isocitrate dehydrogenase mechanism appears to be the major source of NADPH in fat and possibly also liver cells.<ref name=Palmer>{{cite web| vauthors = Palmer M |title=10.4.3 Supply of NADPH for fatty acid synthesis|url=http://watcut.uwaterloo.ca/webnotes/Metabolism/page-10.4.3.html|work=Metabolism Course Notes|access-date=6 April 2012|url-status=dead|archive-url=https://web.archive.org/web/20130606001732/http://watcut.uwaterloo.ca/webnotes/Metabolism/page-10.4.3.html|archive-date=6 June 2013}}</ref> These processes are also found in bacteria. Bacteria can also use a NADP-dependent ] for the same purpose. Like the pentose phosphate pathway, these pathways are related to parts of ].<ref name="pmid26284036"/> Another carbon metabolism-related pathway involved in the generation of NADPH is the mitochondrial folate cycle, which uses principally serine as a source of one-carbon units to sustain nucleotide synthesis and redox homeostasis in mitochondria. Mitochondrial folate cycle has been recently suggested as the principal contributor to NADPH generation in mitochondria of cancer cells.<ref>{{cite journal | vauthors = Ciccarese F, Ciminale V | title = Escaping Death: Mitochondrial Redox Homeostasis in Cancer Cells | journal = Frontiers in Oncology | volume = 7 | pages = 117 | date = June 2017 | pmid = 28649560 | pmc = 5465272 | doi = 10.3389/fonc.2017.00117 | doi-access = free }}</ref> |
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<center> |
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<gallery> |
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Image:NADP-3D-balls.png|<center>] of NADP+</center> |
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Image:NADPH-3D-balls.png|<center>Ball-and-stick model of NADPH</center> |
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</gallery> |
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</center> |
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NADPH can also be generated through pathways unrelated to carbon metabolism. The ferredoxin reductase is such an example. ] transfers the hydrogen between NAD(P)H and NAD(P)<sup>+</sup>, and is found in eukaryotic mitochondria and many bacteria. There are versions that depend on a ] to work and ones that do not. Some anaerobic organisms use ], ripping a hydride from hydrogen gas to produce a proton and NADPH.<ref name="pmid26284036"/> |
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==See also== |
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* ] |
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Like ], NADPH is ]. NADPH in aqueous solution excited at the nicotinamide absorbance of ~335 nm (near UV) has a fluorescence emission which peaks at 445-460 nm (violet to blue). NADP{{+}} has no appreciable fluorescence.<ref name="Blacker Mann Gale Ziegler p. ">{{cite journal | vauthors = Blacker TS, Mann ZF, Gale JE, Ziegler M, Bain AJ, Szabadkai G, Duchen MR | title = Separating NADH and NADPH fluorescence in live cells and tissues using FLIM | journal = Nature Communications | volume = 5 | issue = 1 | pages = 3936 | date = May 2014 | pmid = 24874098 | pmc = 4046109 | doi = 10.1038/ncomms4936 | publisher = Springer Science and Business Media LLC | bibcode = 2014NatCo...5.3936B | doi-access = free }}</ref> |
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{{Enzyme cofactors}} |
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== Function == |
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NADPH provides the reducing agents, usually hydrogen atoms, for biosynthetic reactions and the ] involved in protecting against the toxicity of ] (ROS), allowing the regeneration of ] (GSH).<ref>{{cite journal | vauthors = Rush GF, Gorski JR, Ripple MG, Sowinski J, Bugelski P, Hewitt WR | title = Organic hydroperoxide-induced lipid peroxidation and cell death in isolated hepatocytes | journal = Toxicology and Applied Pharmacology | volume = 78 | issue = 3 | pages = 473–483 | date = May 1985 | pmid = 4049396 | doi = 10.1016/0041-008X(85)90255-8 | bibcode = 1985ToxAP..78..473R }}</ref> NADPH is also used for ] pathways, such as ], steroid synthesis,<ref name=":0">{{Cite book| vauthors = Rodwell V |title=Harper's illustrated Biochemistry, 30th edition|publisher=McGraw Hill|year=2015|isbn=978-0-07-182537-5|location=USA|pages=123–124, 166, 200–201}}</ref> ascorbic acid synthesis,<ref name=":0" /> xylitol synthesis,<ref name=":0" /> cytosolic fatty acid synthesis<ref name=":0" /> and microsomal ]. |
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The NADPH system is also responsible for generating free radicals in immune cells by ]. These radicals are used to destroy pathogens in a process termed the ].<ref>{{cite journal | vauthors = Ogawa K, Suzuki K, Okutsu M, Yamazaki K, Shinkai S | title = The association of elevated reactive oxygen species levels from neutrophils with low-grade inflammation in the elderly | journal = Immunity & Ageing | volume = 5 | pages = 13 | date = October 2008 | pmid = 18950479 | pmc = 2582223 | doi = 10.1186/1742-4933-5-13 | doi-access = free }}</ref> |
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It is the source of reducing equivalents for ] ] of ], ]s, ]s, and ]s. |
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== Stability == |
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NADH and NADPH are very stable in basic solutions, but NAD<sup>+</sup> and NADP<sup>+</sup> are degraded in basic solutions into a fluorescent product that can be used conveniently for quantitation. Conversely, NADPH and NADH are degraded by acidic solutions while NAD<sup>+</sup>/NADP<sup>+</sup> are fairly stable to acid.<ref name="Passonneau1993">{{cite book | vauthors = Passonneau J | title=Enzymatic analysis : a practical guide | publisher=Humana Press | publication-place=Totowa, NJ | year=1993 | isbn=978-0-89603-238-5 | oclc=26397387 | page=3,10}}</ref><ref>{{cite journal | vauthors = Lu W, Wang L, Chen L, Hui S, Rabinowitz JD | title = Extraction and Quantitation of Nicotinamide Adenine Dinucleotide Redox Cofactors | journal = Antioxidants & Redox Signaling | volume = 28 | issue = 3 | pages = 167–179 | date = January 2018 | pmid = 28497978 | pmc = 5737638 | doi = 10.1089/ars.2017.7014 }}</ref> |
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== Enzymes that use NADP(H) as a coenzyme == |
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Many enzymes that bind NADP share a common super-secondary structure named named the "Rossmann fold". The initial beta-alpha-beta (βαβ) fold is the most conserved segment of the Rossmann folds. This segment is in contact with the ADP portion of NADP. Therefore, it is also called an "ADP-binding βαβ fold".<ref name="2015-Hanukoglu">{{cite journal |vauthors=Hanukoglu I |title=Proteopedia: Rossmann fold: A beta-alpha-beta fold at dinucleotide binding sites |journal=Biochem Mol Biol Educ |volume=43 |issue=3 |pages=206–9 |date=2015 |pmid=25704928 |doi=10.1002/bmb.20849 |url=}}</ref> |
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* ]: This enzyme is present ubiquitously in most organisms.<ref name="2017-Hanukoglu-JME">{{cite journal | vauthors = Hanukoglu I | title = Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme | journal = Journal of Molecular Evolution | volume = 85 | issue = 5–6 | pages = 205–218 | date = December 2017 | pmid = 29177972 | doi = 10.1007/s00239-017-9821-9 | s2cid = 7120148 | bibcode = 2017JMolE..85..205H }}</ref> It transfers two electrons from NADPH to FAD. In vertebrates, it serves as the first enzyme in the chain of mitochondrial P450 systems that synthesize steroid hormones.<ref name="1992-Hanukoglu">{{cite journal | vauthors = Hanukoglu I | title = Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 43 | issue = 8 | pages = 779–804 | date = December 1992 | pmid = 22217824 | doi = 10.1016/0960-0760(92)90307-5 | s2cid = 112729 }}</ref> |
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== Enzymes that use NADP(H) as a substrate == |
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In 2018 and 2019, the first two reports of enzymes that catalyze the removal of the 2' phosphate of NADP(H) in eukaryotes emerged. First the ]ic protein MESH1 ({{uniprot|Q8N4P3}}),<ref name="Ding 2018">{{Cite journal |vauthors=Ding CK, Rose J, Wu J, Sun T, Chen KY, Chen PH, Xu E, Tian S, Akinwuntan J, Guan Z, Zhou P, Chi JT | biorxiv = 10.1101/325266 |doi=10.1038/s42255-020-0181-1 | title = MESH1 is a cytosolic NADPH phosphatase that regulates ferroptosis| journal = Nature Metabolism | date = 2020 | volume = 2 | issue = 3 | pages = 270–277 | pmid = 32462112 | pmc = 7252213 }}</ref> then the ] protein ]<ref name="Estrella 2019">{{cite journal | vauthors = Estrella MA, Du J, Chen L, Rath S, Prangley E, Chitrakar A, Aoki T, Schedl P, Rabinowitz J, Korennykh A | title = The metabolites NADP<sup>+</sup> and NADPH are the targets of the circadian protein Nocturnin (Curled) | journal = Nature Communications | date = 2019 | volume = 10 | issue = 1 | page = 2367 | biorxiv = 10.1101/534560 |doi=10.1038/s41467-019-10125-z |doi-access=free | pmid = 31147539 | pmc = 6542800 | bibcode = 2019NatCo..10.2367E }}</ref> were reported. Of note, the structures and NADPH binding of MESH1 () and nocturnin () are not related. |
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{{Gallery |
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| title=]s of NADP+ and NADPH |
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| File:NADP-3D-balls.png|alt1=NADP+|NADP+ |
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| File:NADPH-3D-balls.png|alt2=NADPH|NADPH}} |
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==References== |
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== References == |
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{{Reflist}} |
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{{Reflist}} |
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{{Enzyme cofactors}} |
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{{DEFAULTSORT:Nicotinamide Adenine Dinucleotide Phosphate}} |
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{{DEFAULTSORT:Nicotinamide Adenine Dinucleotide Phosphate}} |
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