Ribose 5-phosphate (R5P) is both a product and an intermediate of the

pentose phosphate pathway The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt and the HMP Shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-pho ...

. The last step of the oxidative reactions in the pentose phosphate pathway is the production of

ribulose 5-phosphate Ribulose 5-phosphate is one of the end-products of the pentose phosphate pathway. It is also an intermediate in the Calvin cycle The Calvin cycle, light-independent reactions, bio synthetic phase, dark reactions, or photosynthetic carbon reducti ...

. Depending on the body's state, ribulose 5-phosphate can reversibly isomerize to ribose 5-phosphate. Ribulose 5-phosphate can alternatively undergo a series of isomerizations as well as transaldolations and transketolations that result in the production of other pentose phosphates as well as

fructose 6-phosphate Fructose 6-phosphate (sometimes called the Neuberg ester) is a derivative of fructose, which has been phosphorylated at the 6-hydroxy group. It is one of several possible fructosephosphates. The β-D-form of this compound is very common in cells. ...

and

glyceraldehyde 3-phosphate Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GA3P, GADP, GAP, TP, GALP or PGAL, is a metabolite that occurs as an intermediate in several central pathways of all organisms.Nelson, D ...

(both intermediates in glycolysis). The enzyme

ribose-phosphate diphosphokinase Ribose-phosphate diphosphokinase (or phosphoribosyl pyrophosphate synthetase or ribose-phosphate pyrophosphokinase) is an enzyme that converts ribose 5-phosphate into phosphoribosyl pyrophosphate (PRPP). It is classified under . The enzyme is i ...

converts ribose-5-phosphate into

phosphoribosyl pyrophosphate Phosphoribosyl pyrophosphate (PRPP) is a pentose phosphate. It is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, as well as in pyrimidine nucleotide formation. Hence it is a building block for DN ...

Structure

R5P consists of a five-carbon sugar,

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 compo ...

, and a

phosphate 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 orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

group at the five-position carbon. It can exist in open chain form or in

furanose A furanose is a collective term for carbohydrates that have a chemical structure that includes a five-membered ring system consisting of four carbon atoms and one oxygen atom. The name derives from its similarity to the oxygen heterocycle furan, bu ...

form. The furanose form is most commonly referred to as ribose 5-phosphoric acid.

Biosynthesis

The formation of R5P is highly dependent on the cell growth and the need for NADPH (

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 NAD ...

), R5P, and ATP (

Adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms o ...

). Formation of each molecule is controlled by the flow of glucose 6-phosphate (G6P) in two different metabolic pathways: the pentose phosphate pathway and glycolysis. The relationship between the two pathways can be examined through different metabolic situations.

Pentose phosphate pathway

R5P is produced in the

in all organisms. The pentose phosphate pathway (PPP) is a metabolic pathway that runs parallel to glycolysis. It is a crucial source for NADPH generation for reductive biosynthesis (e.g.

fatty acid synthesis In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases. This process takes place in the cytoplasm of the cell. Most of the acetyl-CoA which is co ...

) and

pentose In chemistry, a pentose is a monosaccharide (simple sugar) with five carbon atoms. The chemical formula of many pentoses is , and their molecular weight is 150.13 g/mol.NADP+ 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 NAD ...

are reduced to NADPH through the conversion of G6P to

(Ru5P). In the non-oxidative of PPP, Ru5P can be converted to R5P through

ribose-5-phosphate isomerase Ribose-5-phosphate isomerase (Rpi) encoded by the RPIA gene is an enzyme () that catalyzes the conversion between ribose-5-phosphate (R5P) and ribulose-5-phosphate (Ru5P). It is a member of a larger class of isomerases which catalyze the interc ...

enzyme catalysis Enzyme catalysis is the increase in the reaction rate, rate of a process by a Biomolecule, biological molecule, an "enzyme". Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs ...

When demand for NADPH and R5P is balanced, G6P forms one Ru5P molecule through the PPP, generating two NADPH molecules and one R5P molecule.

Glycolysis

When more R5P is needed than NADPH, R5P can be formed through glycolytic intermediates. Glucose 6-phosphate is converted to fructose 6-phosphate (F6P) and glyceraldehyde 3-phosphate (G3P) during glycolysis.

Transketolase Transketolase (abbreviated as TK) is an enzyme that is encoded by the TKT gene. It participates in both the pentose phosphate pathway in all organisms and the Calvin cycle of photosynthesis. Transketolase catalyzes two important reactions, whic ...

and transaldolase convert two molecules of F6P and one molecule of G3P to three molecules of R5P. During rapid cell growth, higher quantities of R5P and NADPH are needed for nucleotide and fatty acid synthesis, respectively. Glycolytic intermediates can be diverted toward the non-oxidative phase of PPP by the expression of the gene for pyruvate kinase isozyme, PKM. PKM creates a bottleneck in the glycolytic pathway, allowing intermediates to be utilized by the PPP to synthesize NADPH and R5P. This process is further enabled by triosephosphate isomerase inhibition by phosphoenolpyruvate, the PKM substrate.

Function

R5P and its derivatives serve as precursors to many biomolecules, including DNA, RNA, ATP, coenzyme A, FAD (Flavin adenine dinucleotide), and histidine.

Nucleotide biosynthesis

Nucleotides serve as the building blocks for nucleic acids, DNA and RNA. They are composed of a nitrogenous base, a pentose sugar, and at least one phosphate group. Nucleotides contain either a purine or a pyrimidine nitrogenous base. All intermediates in purine biosynthesis are constructed on a R5P "scaffold". R5P also serves as an important precursor to pyrimidine ribonucleotide synthesis. During nucleotide biosynthesis, R5P undergoes activation by

(PRPS1) to form

(PRPP). Formation of PRPP is essential for both the Purine metabolism, de novo synthesis of purines and for the purine salvage pathway. The de novo synthesis pathway begins with the activation of R5P to PRPP, which is later catalyzed to become phosphoribosylamine, a nucleotide precursor. During the purine salvage pathway, phosphoribosyltransferases add PRPP to bases. R5pactivation

PRPP also plays an important role in pyrimidine ribonucleotide synthesis. During the fifth step of pyrimidine nucleotide synthesis, PRPP covalently links to orotate at the one-position carbon on the ribose unit. The reaction is catalyzed by Orotate phosphoribosyltransferase, orotate phosphoriboseyltransferase (PRPP transferase), yielding Orotidine 5'-monophosphate, orotidine monophosphate (OMP).

Histidine biosynthesis

Histidine is an essential amino acid that is not synthesized de novo in humans. Like nucleotides, biosynthesis of histidine is initiated by the conversion of R5P to PRPP. The step of histidine biosynthesis is the condensation of ATP and PRPP by ATP phosphoribosyltransferase, ATP-phosphoribosyl transferase, the rate determining enzyme. Histidine biosynthesis is carefully regulated by feedback inhibition/

Other functions

R5P can be converted to adenosine diphosphate ribose, which binds and activates the TRPM2 ion channel. The reaction is catalyzed by ribose-5-phosphate adenylyltransferase

Disease relevance

Diseases have been linked to R5P imbalances in cells. Cancers and tumors show upregulated production of R5P correlated to increased RNA and DNA synthesis. Ribose-5-phosphate isomerase deficiency, Ribose 5-phosphate isomerase deficiency, the rarest disease in the world, is also linked to an imbalance of R5P. Although the molecular pathology of the disease is poorly understood, hypotheses included decreased RNA synthesis. Another disease linked to R5P is gout. Higher levels of G6P lead to a buildup of glycolytic intermediates, that are diverted to R5P production. R5P converts to PRPP, which forces an overproduction of purines, leading to uric acid build up. Accumulation of PRPP is found in Lesch-Nyhan Syndrome. The build up is caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which leads to decreased nucleotide synthesis and an increase of uric acid production. Superactivity in Ribose-phosphate diphosphokinase, PRPS1, the enzyme that catalyzes the R5P to PRPP, has also been linked to gout, as well as neurodevelopmental impairment and sensorineural deafness.

References

{{Nucleotide metabolism intermediates Organophosphates Monosaccharide derivatives