Nicotinamide

adenine
dinucleotide
phosphate

Nicotinamide adenine dinucleotide

phosphate, abbreviated NADP+ or, in
older notation, TPN (triphosphopyridine
nucleotide), is a cofactor used in
anabolic reactions, such as the Calvin
cycle and lipid and nucleic acid
syntheses, which require NADPH as a
reducing agent. It is used by all forms of
cellular life.[1]
 Nicotinamide adenine dinucleotide
phosphate

Identifiers

CAS Number 53-59-8  

3D model (JSmol) Interactive image

ChEBI CHEBI:44409  

ChEMBL ChEMBL213053  

ChemSpider 5674  

MeSH NADP
PubChem CID 5885
InChI
InChI=1S/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(38,3
9)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 
Key: XJLXINKUBYWONI-NNYOXOHSSA-N 

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(38,3
9)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
Key: XJLXINKUBYWONI-NNYOXOHSBN

SMILES
O=C(N)c1ccc[n+](c1)[C@H]2[C@H](O)[C@H](O)[C@H](O2)COP([O-])(=O)OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c4ncnc5N)[C
@@H]([C@@H]3O)OP(=O)(O)O

Properties

Chemical formula C21H29N7O17P3

Molar mass 744.416 g·mol−1

Except where otherwise noted, data are
given for materials in their standard state (at
25 °C [77 °F], 100 kPa).

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Infobox references

NADPH is the reduced form of NADP+.

NADP+ differs from NAD+ by the
presence of an additional phosphate
group on the 2' position of the ribose ring
that carries the adenine moiety. This
extra phosphate is added by NAD+ kinase
and removed by NADP+ phosphatase.[2]

Biosynthesis

NADP+ …

In general, NADP+ is synthesized before

NADPH is. Such a reaction usually starts
with NAD+ from either the de-novo or the
salvage pathway, with NAD+ kinase
adding the extra phosphate group.
NAD(P)+ nucleosidase allows for
synthesis from nicotinamide in the
salvage pathway, and NADP+
phosphatase can convert NADPH back
to NADH to maintain a balance.[1] Some
forms of the NAD+ kinase, notably the
one in mitochondria, can also accept
NADH to turn it directly into NADPH.[3][4]
The prokaryotic pathway is less well
understood, but with all the similar
proteins the process should work in a
similar way.[1]

NADPH …

NADPH is produced from NADP+. The

major source of NADPH in animals and
other non-photosynthetic organisms is
the pentose phosphate pathway, by
glucose-6-phosphate dehydrogenase
(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 Entner–
Doudoroff pathway, but NADPH
production remains the same.[1]

Ferredoxin-NADP+ reductase, 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 light reactions of
photosynthesis. It is used as reducing
power for the biosynthetic reactions in
the Calvin cycle 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
nitrogen cycle and in the production of
oils.[1]

There are several other lesser-known

mechanisms of generating NADPH, all of
which depend on the presence of
mitochondria in eukaryotes. The key
enzymes in these carbon-metabolism-
related processes are NADP-linked
isoforms of malic enzyme, isocitrate
dehydrogenase (IDH), and glutamate
dehydrogenase. In these reactions,
NADP+ acts like NAD+ in other enzymes
as an oxidizing agent.[5] The isocitrate
dehydrogenase mechanism appears to
be the major source of NADPH in fat and
possibly also liver cells.[6] These
processes are also found in bacteria.
Bacteria can also use a NADP-dependent
glyceraldehyde 3-phosphate
dehydrogenase for the same purpose.
Like the pentose phosphate pathway,
these pathways are related to parts of
glycolysis.[1]

NADPH can also be generated through

pathways unrelated to carbon
metabolism. The ferredoxin reductase is
such an example. Nicotinamide
nucleotide transhydrogenase transfers
the hydrogen between NAD(P)H and
NAD(P)+, and is found in eukaryotic
mitochondria and many bacteria. There
are versions that depend on a proton
gradient to work and ones that do not.
Some anaerobic organisms use NADP+-
linked hydrogenase, ripping a hydride
from hydrogen gas to produce a proton
and NADPH.[1]

Function
NADPH provides the reducing
equivalents for biosynthetic reactions
and the oxidation-reduction involved in
protecting against the toxicity of reactive
oxygen species (ROS), allowing the
regeneration of glutathione (GSH).[7]
NADPH is also used for anabolic
pathways, such as cholesterol synthesis,
steroid synthesis,[8] ascorbic acid
synthesis,[8] xylitol synthesis,[8] cytosolic
fatty acid synthesis[8] and microsomal
fatty acid chain elongation.

The NADPH system is also responsible

for generating free radicals in immune
cells by NADPH oxidase. These radicals
are used to destroy pathogens in a
process termed the respiratory burst.[9] It
is the source of reducing equivalents for
cytochrome P450 hydroxylation of
aromatic compounds, steroids, alcohols,
and drugs.

Enzymes that use NADP(H)

as a coenzyme
Adrenodoxin reductase: This enzyme
is present ubiquitously in most
organisms.[10] 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.[11]

Enzymes that use NADP(H)

as a substrate
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 cytoplasmic protein
MESH1 (Q8N4P3),[12] then the
mitochondrial protein nocturnin[13][14]
were reported. Of note, the structures
and NADPH binding of MESH1 (5VXA )
and nocturnin (6NF0 ) are not related.

Ball-and-stick models of NADP+ and

NADPH
NADP+

NADPH
References
1. Spaans SK, Weusthuis RA, van der
Oost J, Kengen SW (2015). "NADPH-
generating systems in bacteria and
archaea" . Frontiers in Microbiology.
6: 742.
doi:10.3389/fmicb.2015.00742 .
PMC 4518329 . PMID 26284036 .
2. Kawai S, Murata K (April 2008).
"Structure and function of NAD
kinase and NADP phosphatase: key
enzymes that regulate the
intracellular balance of NAD(H) and
NADP(H)" . Bioscience,
Biotechnology, and Biochemistry. 72
(4): 919–30.
doi:10.1271/bbb.70738 .
PMID 18391451 .
3. Iwahashi Y, Hitoshio A, Tajima N,
Nakamura T (April 1989).
"Characterization of NADH kinase
from Saccharomyces cerevisiae".
Journal of Biochemistry. 105 (4):
588–93.
doi:10.1093/oxfordjournals.jbchem.
a122709 . PMID 2547755 .
4. Iwahashi Y, Nakamura T (June
1989). "Localization of the NADH
kinase in the inner membrane of
yeast mitochondria". Journal of
Biochemistry. 105 (6): 916–21.
doi:10.1093/oxfordjournals.jbchem.
a122779 . PMID 2549021 .
5. Hanukoglu I, Rapoport R (Feb–May
1995). "Routes and regulation of
NADPH production in steroidogenic
mitochondria". Endocrine Research.
21 (1–2): 231–41.
doi:10.3109/07435809509030439 .
PMID 7588385 .
6. Palmer, Michael. "10.4.3 Supply of
NADPH for fatty acid synthesis" .
Metabolism Course Notes. Archived
from the original on 6 June 2013.
Retrieved 6 April 2012.
7. Rush GF, Gorski JR, Ripple MG,
Sowinski J, Bugelski P, Hewitt WR
(May 1985). "Organic hydroperoxide-
induced lipid peroxidation and cell
death in isolated hepatocytes".
Toxicology and Applied
Pharmacology. 78 (3): 473–83.
doi:10.1016/0041-008X(85)90255-
8 . PMID 4049396 .
8. Rodwell, Victor (2015). Harper's
illustrated Biochemistry, 30th edition.
USA: McGraw Hill. pp. 123–124, 166,
200–201. ISBN 978-0-07-182537-5.
9. Ogawa K, Suzuki K, Okutsu M,
Yamazaki K, Shinkai S (October
2008). "The association of elevated
reactive oxygen species levels from
neutrophils with low-grade
inflammation in the elderly" .
Immunity & Ageing. 5: 13.
doi:10.1186/1742-4933-5-13 .
PMC 2582223 . PMID 18950479 .
10. Hanukoglu I (December 2017).
"Conservation of the Enzyme-
Coenzyme Interfaces in FAD and
NADP Binding Adrenodoxin
Reductase-A Ubiquitous Enzyme".
Journal of Molecular Evolution. 85
(5–6): 205–218.
Bibcode:2017JMolE..85..205H .
doi:10.1007/s00239-017-9821-9 .
PMID 29177972 .
11. Hanukoglu I (December 1992).
"Steroidogenic enzymes: structure,
function, and role in regulation of
steroid hormone biosynthesis" . The
Journal of Steroid Biochemistry and
Molecular Biology. 43 (8): 779–804.
doi:10.1016/0960-0760(92)90307-
5 . PMID 22217824 .
12. Ding CKC, Rose J, Wu J, Sun T, Chen
KY, Chen PH, Xu E, Tian S,
Akinwuntan J, Guan Z, Zhou P, Chi
JTA (2018). "Mammalian stringent-
like response mediated by the
cytosolic NADPH phosphatase
MESH1" . bioRxiv.
doi:10.1101/325266 .
13. Estrella MA, Du J, Chen L, Rath S,
Prangley E, Chitrakar A, Aoki T,
Schedl P, Rabinowitz J, Korennykh A
(2019). "The Metabolites NADP+ and
NADPH are the Targets of the
Circadian Protein Nocturnin
(Curled)" . bioRxiv.
doi:10.1101/534560 .
14. Estrella MA, Du J, Chen L, Rath S,
Prangley E, Chitrakar A, et al. (May
2019). "+ and NADPH are the targets
of the circadian protein Nocturnin
(Curled)" . Nature Communications.
10 (1): 2367. doi:10.1038/s41467-
019-10125-z . PMC 6542800 .
PMID 31147539 .
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