Triphosphopyridine Nucleotide
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Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in
anabolic reaction Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...
s, such as the
Calvin cycle The Calvin cycle, light-independent reactions, bio synthetic phase, dark reactions, or photosynthetic carbon reduction (PCR) cycle of photosynthesis is a series of chemical reactions that convert carbon dioxide and hydrogen-carrier compounds into ...
and
lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...
and
nucleic acid Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a pentose, 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nuclei ...
syntheses, which require NADPH as a
reducing agent In chemistry, a reducing agent (also known as a reductant, reducer, or electron donor) is a chemical species that "donates" an electron to an (called the , , , or ). Examples of substances that are common reducing agents include hydrogen, carbon ...
('hydrogen source'). NADPH is the
reduced Reduction, reduced, or reduce may refer to: Science and technology Chemistry * Reduction (chemistry), part of a reduction-oxidation (redox) reaction in which atoms have their oxidation state changed. ** Organic redox reaction, a redox reacti ...
form, whereas NADP is the
oxidized Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
form. NADP is used by all forms of cellular life. NADP is essential for life because it is needed for cellular respiration. NADP differs from
NAD NAD or Nad may refer to: Geography * Nad, County Cork, a village in Ireland * North American Datum, a series of geographic coordinate systems * North Atlantic Drift, an Atlantic Ocean current * Hobli, a subdivision of a taluka in southern Ind ...
by the presence of an additional
phosphate group Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosp ...
on the 2' position of the
ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally occurring form, , is a component of the ribonucleotides from which RNA is built, and so this comp ...
ring that carries the
adenine Adenine (, ) (nucleoside#List of nucleosides and corresponding nucleobases, symbol A or Ade) is a purine nucleotide base that is found in DNA, RNA, and Adenosine triphosphate, ATP. Usually a white crystalline subtance. The shape of adenine is ...
moiety Moiety may refer to: __NOTOC__ Anthropology * Moiety (kinship), either of two groups into which a society is divided ** A division of society in the Iroquois societal structure in North America ** An Australian Aboriginal kinship group ** Native Ha ...
. This extra phosphate is added by NAD+ kinase and removed by NADP+ phosphatase.


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.
ADP-ribosyl cyclase In enzymology, a ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase () is a bifunctional enzyme that catalysis, catalyzes the chemical reaction :NAD+ + H2O \rightleftharpoons cADPR + H2O + nicotinamide \rightleftharpoons ADP-ribose + nicotinamide T ...
allows for synthesis from
nicotinamide Nicotinamide (International nonproprietary name, INN, British Approved Name, BAN ) or niacinamide (United States Adopted Name, USAN ) is a form of vitamin B3, vitamin B3 found in food and used as a dietary supplement and medication. As a suppl ...
in the salvage pathway, and NADP+ phosphatase can convert NADPH back to NADH to maintain a balance. Some forms of the NAD+ kinase, notably the one in mitochondria, can also accept NADH to turn it directly into NADPH. The prokaryotic pathway is less well understood, but with all the similar proteins the process should work in a similar way.


NADPH

NADPH is produced from NADP+. The major source of NADPH in animals and other non-photosynthetic organisms is the
pentose phosphate pathway The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt or HMP shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (five-carbon sugars) as well as ribose 5-ph ...
, by
glucose-6-phosphate dehydrogenase Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) () is a cytosolic enzyme that catalysis, catalyzes the chemical reaction : Glucose 6-phosphate, D-glucose 6-phosphate + NADP+ + 6-Phosphogluconolactone, 6-phospho-D-glucono-1,5-lactone + NADPH ...
(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 The Entner–Doudoroff pathway (ED Pathway) is a metabolic pathway that is most notable in Gram-negative bacteria, certain Gram-positive bacteria and archaea. Glucose is the substrate in the ED pathway and, through a series of enzyme assisted chemi ...
, but NADPH production remains the same. 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 Light-dependent reactions are certain photochemical reactions involved in photosynthesis, the main process by which plants acquire energy. There are two light dependent reactions: the first occurs at Photosystem II, photosystem II (PSII) and the ...
of
photosynthesis Photosynthesis ( ) is a system of biological processes by which photosynthetic organisms, such as most plants, algae, and cyanobacteria, convert light energy, typically from sunlight, into the chemical energy necessary to fuel their metabo ...
. It is used as reducing power for the biosynthetic reactions in the
Calvin cycle The Calvin cycle, light-independent reactions, bio synthetic phase, dark reactions, or photosynthetic carbon reduction (PCR) cycle of photosynthesis is a series of chemical reactions that convert carbon dioxide and hydrogen-carrier compounds into ...
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 The nitrogen cycle is the biogeochemical cycle by which nitrogen is converted into multiple chemical forms as it circulates among atmosphere, atmospheric, terrestrial ecosystem, terrestrial, and marine ecosystems. The conversion of nitrogen can ...
and in the production of oils. There are several other lesser-known mechanisms of generating NADPH, all of which depend on the presence of
mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
in eukaryotes. The key enzymes in these carbon-metabolism-related processes are NADP-linked isoforms of
malic enzyme Malic enzyme (ME) may refer to '' decarboxylating'' malate dehydrogenases: * Malate dehydrogenase (decarboxylating) () or NAD-malic enzyme * Malate dehydrogenase (oxaloacetate-decarboxylating) (), another NAD-malic enzyme * Malate dehydrogenase ...
,
isocitrate dehydrogenase Isocitrate dehydrogenase (IDH) () and () is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2. This is a two-step process, which involves oxidation of isocitrate ( ...
(IDH), and
glutamate dehydrogenase Glutamate dehydrogenase (GLDH, GDH) is an enzyme observed in both prokaryotes and eukaryotic mitochondria. The aforementioned reaction also yields ammonia, which in eukaryotes is canonically processed as a substrate in the urea cycle. Typic ...
. In these reactions, NADP+ acts like NAD+ in other enzymes as an oxidizing agent. The isocitrate dehydrogenase mechanism appears to be the major source of NADPH in fat and possibly also liver cells. These processes are also found in bacteria. Bacteria can also use a NADP-dependent
glyceraldehyde 3-phosphate dehydrogenase Glyceraldehyde 3-phosphate dehydrogenase (abbreviated GAPDH) () is an enzyme of about 37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long establis ...
for the same purpose. Like the pentose phosphate pathway, these pathways are related to parts of
glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvic acid, pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The Thermodynamic free energy, free energy released in this process is used to form ...
. 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. NADPH can also be generated through pathways unrelated to carbon metabolism. The ferredoxin reductase is such an example.
Nicotinamide nucleotide transhydrogenase Nicotinamide nucleotide transhydrogenase may stand for * NAD(P)+ transhydrogenase (Re/Si-specific) * NAD(P)+ transhydrogenase (Si-specific) * NNT (gene) {{Short pages monitor