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 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 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 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. 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, 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 ...

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 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, 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 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 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. 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 agents, usually hydrogen atoms, for biosynthetic reactions and the oxidation-reduction involved in protecting against the toxicity of

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

(ROS), allowing the regeneration of glutathione (GSH). NADPH is also used for

anabolic Anabolism () is the set of metabolic pathways that construct macromolecules like DNA or RNA from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catab ...

pathways, such as cholesterol synthesis, 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 NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white ...

. These radicals are used to destroy pathogens in a process termed the respiratory burst. It is the source of reducing equivalents for

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

hydroxylation of aromatic compounds,

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

s, and

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

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

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". * 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 The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

ic protein MESH1 (), then the mitochondrial protein nocturnin were reported. Of note, the structures and NADPH binding of MESH1
5VXA
and nocturnin
6NF0
are not related.

References

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