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
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 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 cl ...
syntheses, which require NADPH as a
reducing agent ('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 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 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. 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 atmospheric, terrestrial, and marine ecosystems. The conversion of nitrogen can be carried out through both biologi ...
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 Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
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 establishe ...
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 pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
.
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. 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 (ROS), allowing the regeneration of
glutathione (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.
It is the source of reducing equivalents for
cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
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 a ...
s,
alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
s, 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 insuffla ...
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
cytoplasmic 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 use ...
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