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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 el, μεταβολή ''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 cell ...
s, such as the Calvin cycle and
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids incl ...
and
nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main ...
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 commonly reducing agents include the Earth m ...
('hydrogen source'). It is used by all forms of cellular life. 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 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 compou ...
ring that carries the adenine
moiety Moiety may refer to: Chemistry * Moiety (chemistry), a part or functional group of a molecule ** Moiety conservation, conservation of a subgroup in a chemical species Anthropology * Moiety (kinship), either of two groups into which a society is ...
. 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 catalyzes the chemical reaction :NAD+ + H2O \rightleftharpoons cADPR + H2O + nicotinamide \rightleftharpoons ADP-ribose + nicotinamide The 3 sub ...
allows for synthesis from
nicotinamide Niacinamide or Nicotinamide (NAM) is a form of vitamin B3 found in food and used as a dietary supplement and medication. As a supplement, it is used by mouth to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) ma ...
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, 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. 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 is jargon for certain photochemical reactions that are involved in photosynthesis, the main process by which plants acquire energy. There are two light dependent reactions, the first occurs at photosystem II (PSII) and ...
of
photosynthesis Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored i ...
. 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 The nitrogen cycle is the biogeochemical cycle by which nitrogen is converted into multiple chemical forms as it circulates among atmospheric, terrestrial, and marine ecosystems. The conversion of nitrogen can be carried out through both biolo ...
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 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. 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 for the same purpose. Like the pentose phosphate pathway, these pathways are related to parts of glycolysis. 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 synhesis 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 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. Like NADH, NADPH is
fluorescent Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, th ...
. 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.


Function

NADPH provides the reducing equivalents, usually hydrogen atoms, for biosynthetic reactions and the
oxidation-reduction Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
involved in protecting against the toxicity of
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen ...
(ROS), allowing the regeneration of
glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...
(GSH). NADPH is also used for anabolic pathways, such as
cholesterol synthesis The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopenten ...
, steroid synthesis, ascorbic acid synthesis, xylitol synthesis, cytosolic fatty acid synthesis 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 Respiratory burst (or oxidative burst) is the rapid release of the reactive oxygen species (ROS), Superoxide, superoxide anion () and hydrogen peroxide (), from different Cell (biology), cell types. This is usually utilised for mammalian immune sy ...
. It is the source of reducing equivalents for
cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...
hydroxylation In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...
of aromatic compounds,
steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
s, alcohols, and
drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhal ...
s.


Stability

NADH and NADPH are very stable in basic solutions, but NAD+ and NADP+ 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+/NADP+ are fairly stable to acid.


Enzymes that use NADP(H) as a coenzyme

* Adrenodoxin reductase: This enzyme is present ubiquitously in most organisms. 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.


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
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
ic protein MESH1 (), then the
mitochondrial 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 ...
protein
nocturnin Nocturnin is a human hydrolase enzyme that is involved in metabolism and its expression is controlled by the rhythmic circadian clock. It is encoded by the NOCT gene located on chromosome 4. Nocturnin contains a c-terminal structural domain of t ...
were reported. Of note, the structures and NADPH binding of MESH1
5VXA
and nocturnin
6NF0
are not related.


References

{{DEFAULTSORT:Nicotinamide Adenine Dinucleotide Phosphate Nucleotides Coenzymes Pyridinium compounds