Ribose 5-phosphate

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Ribose 5-phosphate
Ribose 5-phosphate.png
Names
IUPAC name
5-O-Phosphono-D-ribose
Other names
Ribose 5-phosphate
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.022.101 OOjs UI icon edit-ltr-progressive.svg
MeSH ribose-5-phosphate
PubChem CID
UNII
  • InChI=1S/C5H11O8P/c6-1-3(7)5(9)4(8)2-13-14(10,11)12/h1,3-5,7-9H,2H2,(H2,10,11,12)/t3-,4+,5-/m0/s1 X mark.svgN
    Key: PPQRONHOSHZGFQ-LMVFSUKVSA-N X mark.svgN
  • InChI=1/C5H11O8P/c6-1-3(7)5(9)4(8)2-13-14(10,11)12/h1,3-5,7-9H,2H2,(H2,10,11,12)/t3-,4+,5-/m0/s1
    Key: PPQRONHOSHZGFQ-LMVFSUKVBC
  • C([C@H]([C@H]([C@H](C=O)O)O)O)OP(=O)(O)O
Properties
C5H11O8P
Molar mass 230.110
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Ribose 5-phosphate (R5P) is both a product and an intermediate of the pentose phosphate pathway. The last step of the oxidative reactions in the pentose phosphate pathway is the production of ribulose 5-phosphate. 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 and glyceraldehyde 3-phosphate (both intermediates in glycolysis).

Contents

The enzyme ribose-phosphate diphosphokinase converts ribose-5-phosphate into phosphoribosyl pyrophosphate.

Structure

Crystal structure of ribose 5-phosphate isomerase and ribose 5-phosphate complex in E. coli RPIA.png
Crystal structure of ribose 5-phosphate isomerase and ribose 5-phosphate complex in E. coli

R5P consists of a five-carbon sugar, ribose, and a phosphate group at the five-position carbon. It can exist in open chain form or in furanose form. The furanose form is most commonly referred to as ribose 5-phosphoric acid. [1]

Biosynthesis

The formation of R5P is highly dependent on the cell growth and the need for NADPH (Nicotinamide adenine dinucleotide phosphate), R5P, and ATP (Adenosine triphosphate). 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. [2]

Pentose phosphate pathway

Conversion of ribose 5-phosphate open chain form to furanose form. Conversion.png
Conversion of ribose 5-phosphate open chain form to furanose form.

R5P is produced in the pentose phosphate pathway in all organisms. [2] 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 [3] (e.g. fatty acid synthesis) and pentose sugars. The pathway consists of two phases: an oxidative phase that generates NADPH and a non-oxidative phase that involves the interconversion of sugars. In the oxidative phase of PPP, two molecules of NADP+ are reduced to NADPH through the conversion of G6P to ribulose 5-phosphate (Ru5P). In the non-oxidative of PPP, Ru5P can be converted to R5P through ribose-5-phosphate isomerase enzyme catalysis. [4]

Isomerization of ribulose 5-phosphate to ribose 5-phosphate. Ru5PtoR5P2.png
Isomerization of ribulose 5-phosphate to ribose 5-phosphate.

When demand for NADPH and R5P is balanced, G6P forms one Ru5P molecule through the PPP, generating two NADPH molecules and one R5P molecule. [2]

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 and transaldolase convert two molecules of F6P and one molecule of G3P to three molecules of R5P. [2] 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. [2]

Function

R5P and its derivatives serve as precursors to many biomolecules, including DNA, RNA, ATP, coenzyme A, FAD (Flavin adenine dinucleotide), and histidine. [5]

Nucleotide biosynthesis

Nucleotides serve as the building blocks for nucleic acids, DNA and RNA. [6] 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". [7] R5P also serves as an important precursor to pyrimidine ribonucleotide synthesis.

During nucleotide biosynthesis, R5P undergoes activation by ribose-phosphate diphosphokinase (PRPS1) to form phosphoribosyl pyrophosphate (PRPP). Formation of PRPP is essential for both the de novo synthesis of purines and for the purine salvage pathway. [8] 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, [9] phosphoribosyltransferases add PRPP to bases. [10]

Activation of ribose 5-phosphate to phosphoribosyl pyrophosphate by ribose-phosphate diphosphokinase. R5pactivation.png
Activation of ribose 5-phosphate to phosphoribosyl pyrophosphate by ribose-phosphate diphosphokinase.

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 phosphoriboseyltransferase (PRPP transferase), yielding orotidine monophosphate (OMP). [8]

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-phosphoribosyl transferase, the rate determining enzyme. Histidine biosynthesis is carefully regulated by feedback inhibition/ [11]

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 [12]

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. [2] Ribose 5-phosphate isomerase deficiency, the rarest disease in the world, [13] [14] 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. [15] 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. [8]

Accumulation of PRPP is found in Lesch-Nyhan Syndrome. [16] 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 PRPS1, the enzyme that catalyzes the R5P to PRPP, has also been linked to gout, as well as neurodevelopmental impairment and sensorineural deafness. [17]

Related Research Articles

<span class="mw-page-title-main">Glycolysis</span> Catabolic pathway

Glycolysis is the metabolic pathway that converts glucose into pyruvate, and in most organisms, occurs in the liquid part of cells, the cytosol. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes.

<span class="mw-page-title-main">Nucleotide</span> Biological molecules that form the building blocks of nucleic acids

Nucleotides are organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.

<span class="mw-page-title-main">Ribonucleotide</span> Nucleotide containing ribose as its pentose component

In biochemistry, a ribonucleotide is a nucleotide containing ribose as its pentose component. It is considered a molecular precursor of nucleic acids. Nucleotides are the basic building blocks of DNA and RNA. Ribonucleotides themselves are basic monomeric building blocks for RNA. Deoxyribonucleotides, formed by reducing ribonucleotides with the enzyme ribonucleotide reductase (RNR), are essential building blocks for DNA. There are several differences between DNA deoxyribonucleotides and RNA ribonucleotides. Successive nucleotides are linked together via phosphodiester bonds.

The term amphibolic is used to describe a biochemical pathway that involves both catabolism and anabolism. Catabolism is a degradative phase of metabolism in which large molecules are converted into smaller and simpler molecules, which involves two types of reactions. First, hydrolysis reactions, in which catabolism is the breaking apart of molecules into smaller molecules to release energy. Examples of catabolic reactions are digestion and cellular respiration, where sugars and fats are broken down for energy. Breaking down a protein into amino acids, or a triglyceride into fatty acids, or a disaccharide into monosaccharides are all hydrolysis or catabolic reactions. Second, oxidation reactions involve the removal of hydrogens and electrons from an organic molecule. Anabolism is the biosynthesis phase of metabolism in which smaller simple precursors are converted to large and complex molecules of the cell. Anabolism has two classes of reactions. The first are dehydration synthesis reactions; these involve the joining of smaller molecules together to form larger, more complex molecules. These include the formation of carbohydrates, proteins, lipids and nucleic acids. The second are reduction reactions, in which hydrogens and electrons are added to a molecule. Whenever that is done, molecules gain energy.

<span class="mw-page-title-main">Glucose 6-phosphate</span> Chemical compound

Glucose 6-phosphate is a glucose sugar phosphorylated at the hydroxy group on carbon 6. This dianion is very common in cells as the majority of glucose entering a cell will become phosphorylated in this way.

A salvage pathway is a pathway in which a biological product is produced from intermediates in the degradative pathway of its own or a similar substance. The term often refers to nucleotide salvage in particular, in which nucleotides are synthesized from intermediates in their degradative pathway.

A nucleoside triphosphate is a nucleoside containing a nitrogenous base bound to a 5-carbon sugar, with three phosphate groups bound to the sugar. They are the molecular precursors of both DNA and RNA, which are chains of nucleotides made through the processes of DNA replication and transcription. Nucleoside triphosphates also serve as a source of energy for cellular reactions and are involved in signalling pathways.

In molecular biology, biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism.

<span class="mw-page-title-main">Pentose phosphate pathway</span> Metabolic process

The pentose phosphate pathway is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses as well as ribose 5-phosphate, a precursor for the synthesis of nucleotides. While the pentose phosphate pathway does involve oxidation of glucose, its primary role is anabolic rather than catabolic. The pathway is especially important in red blood cells (erythrocytes). The reactions of the pathway were elucidated in the early 1950s by Bernard Horecker and co-workers.

<span class="mw-page-title-main">Tumor metabolome</span>

The study of the tumor metabolism, also known as tumor metabolome describes the different characteristic metabolic changes in tumor cells. The characteristic attributes of the tumor metabolome are high glycolytic enzyme activities, the expression of the pyruvate kinase isoenzyme type M2, increased channeling of glucose carbons into synthetic processes, such as nucleic acid, amino acid and phospholipid synthesis, a high rate of pyrimidine and purine de novo synthesis, a low ratio of Adenosine triphosphate and Guanosine triphosphate to Cytidine triphosphate and Uridine triphosphate, low Adenosine monophosphate levels, high glutaminolytic capacities, release of immunosuppressive substances and dependency on methionine.

<span class="mw-page-title-main">Sugar phosphates</span>

Sugar phosphates are often used in biological systems to store or transfer energy. They also form the backbone for DNA and RNA. Sugar phosphate backbone geometry is altered in the vicinity of the modified nucleotides.

<span class="mw-page-title-main">Phosphoribosyl pyrophosphate</span> Chemical compound

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 DNA and RNA. The vitamins thiamine and cobalamin, and the amino acid tryptophan also contain fragments derived from PRPP. It is formed from ribose 5-phosphate (R5P) by the enzyme ribose-phosphate diphosphokinase:

<span class="mw-page-title-main">Nucleic acid metabolism</span> Process

Nucleic acid metabolism is a collective term that refers to the variety of chemical reactions by which nucleic acids are either synthesized or degraded. Nucleic acids are polymers made up of a variety of monomers called nucleotides. Nucleotide synthesis is an anabolic mechanism generally involving the chemical reaction of phosphate, pentose sugar, and a nitrogenous base. Degradation of nucleic acids is a catabolic reaction and the resulting parts of the nucleotides or nucleobases can be salvaged to recreate new nucleotides. Both synthesis and degradation reactions require multiple enzymes to facilitate the event. Defects or deficiencies in these enzymes can lead to a variety of diseases.

Pyrimidine biosynthesis occurs both in the body and through organic synthesis.

<span class="mw-page-title-main">6-phosphogluconolactonase</span> Cytosolic enzyme

6-Phosphogluconolactonase (EC 3.1.1.31, 6PGL, PGLS, systematic name 6-phospho-D-glucono-1,5-lactone lactonohydrolase) is a cytosolic enzyme found in all organisms that catalyzes the hydrolysis of 6-phosphogluconolactone to 6-phosphogluconic acid in the oxidative phase of the pentose phosphate pathway:

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

<span class="mw-page-title-main">Ribose-phosphate diphosphokinase</span> Class of enzymes

Ribose-phosphate diphosphokinase is an enzyme that converts ribose 5-phosphate into phosphoribosyl pyrophosphate (PRPP). It is classified under EC 2.7.6.1.

<span class="mw-page-title-main">Ribose-5-phosphate isomerase</span>

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 interconversion of chemical isomers. It plays a vital role in biochemical metabolism in both the pentose phosphate pathway and the Calvin cycle. The systematic name of this enzyme class is D-ribose-5-phosphate aldose-ketose-isomerase.

<span class="mw-page-title-main">Inborn errors of carbohydrate metabolism</span> Medical condition

Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.

<span class="mw-page-title-main">5-Aminoimidazole ribotide</span> Chemical compound

5′-Phosphoribosyl-5-aminoimidazole is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments derived from AIR. It is an intermediate in the adenine pathway and is synthesized from 5′-phosphoribosylformylglycinamidine by AIR synthetase.

References

  1. ↑ Levene PA, Stiller ET (February 1934). "The Synthesis of Ribose-5-Phosphoric Acid". Journal of Biological Chemistry. 104 (2): 299–306.
  2. 1 2 3 4 5 6 Berg JM, Tymoczko JL, Stryer L (2015). Biochemistry (7th ed.). W.H. Freeman. pp. 589–613. ISBN   978-1-4292-7635-1.
  3. ↑ Kruger NJ, von Schaewen A (June 2003). "The oxidative pentose phosphate pathway: structure and organisation". Current Opinion in Plant Biology. 6 (3): 236–46. doi:10.1016/s1369-5266(03)00039-6. PMID   12753973.
  4. ↑ Zhang R, Andersson CE, Savchenko A, Skarina T, Evdokimova E, Beasley S, Arrowsmith CH, Edwards AM, Joachimiak A, Mowbray SL (January 2003). "Structure of Escherichia coli ribose-5-phosphate isomerase: a ubiquitous enzyme of the pentose phosphate pathway and the Calvin cycle". Structure. 11 (1): 31–42. doi:10.1016/s0969-2126(02)00933-4. PMC   2792023 . PMID   12517338.
  5. ↑ Coleman JP, Smith CJ (2007). X Pharm: The Comprehensive Pharmacology Reference. pp. 1–6. doi:10.1016/b978-008055232-3.60227-2. ISBN   9780080552323.
  6. ↑ "Nucleotides". IUPAC Compendium of Chemical Terminology. International Union of Pure and Applied Chemistry. 2009. doi:10.1351/goldbook.n04255. ISBN   978-0-9678550-9-7.
  7. ↑ Engelking LR (2015). "Purine Biosynthesis". Textbook of Veterinary Physiological Chemistry (Third ed.). pp. 88–92. doi:10.1016/b978-0-12-391909-0.50015-3. ISBN   978-0-12-391909-0.
  8. 1 2 3 Pelley JW (2011). "Purine, Pyrimidine, and Single-Carbon Metabolism". Elsevier's Integrated Review Biochemistry (2nd ed.). pp. 119–124. doi:10.1016/b978-0-323-07446-9.00014-3. ISBN   9780323074469.
  9. ↑ Engelking LR (2015). "Chapter 31 — Carbohydrate Metabolism in Erythrocytes". Textbook of Veterinary Physiological Chemistry (Third ed.). pp. 190–194. doi:10.1016/b978-0-12-391909-0.50031-1. ISBN   978-0-12-391909-0.
  10. ↑ Schramm VL, Grubmeyer C (2004). Phosphoribosyltransferase Mechanisms and Roles in Nucleic Acid Metabolism. pp. 261–304. doi:10.1016/s0079-6603(04)78007-1. ISBN   9780125400787. PMID   15210333.{{cite book}}: |journal= ignored (help)
  11. ↑ Ingle RA (January 2011). "Histidine biosynthesis". The Arabidopsis Book. 9: e0141. doi:10.1199/tab.0141. PMC   3266711 . PMID   22303266.
  12. ↑ Evans WR, San Pietro A (January 1966). "Phosphorolysis of adenosine diphosphoribose". Archives of Biochemistry and Biophysics. 113 (1): 236–44. doi:10.1016/0003-9861(66)90178-0. PMID   4287446.
  13. ↑ Wamelink MM, Grüning NM, Jansen EE, Bluemlein K, Lehrach H, Jakobs C, Ralser M (September 2010). "The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency". Journal of Molecular Medicine. 88 (9): 931–9. doi:10.1007/s00109-010-0634-1. hdl:1871/34686. PMID   20499043.
  14. ↑ Huck JH, Verhoeven NM, Struys EA, Salomons GS, Jakobs C, van der Knaap MS (April 2004). "Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy". American Journal of Human Genetics. 74 (4): 745–51. doi:10.1086/383204. PMC   1181951 . PMID   14988808.
  15. ↑ Jiménez RT, Puig JG (2012). "Purine Metabolism in the Pathogenesis of Hyperuricemia and Inborn Errors of Purine Metabolism Associated With Disease". Gout & Other Crystal Arthropathies. pp. 36–50. doi:10.1016/b978-1-4377-2864-4.10003-x. ISBN   978-1-4377-2864-4.
  16. ↑ Ichida K, Hosoyamada M, Hosoya T, Endou H (2009). "Primary Metabolic and Renal Hyperuricemia". Genetic Diseases of the Kidney. pp. 651–660. doi:10.1016/b978-0-12-449851-8.00038-3. ISBN   978-0-12-449851-8.
  17. ↑ Singer HS, Mink JW, Gilbert DL, Jankovic J (2010). "Inherited Metabolic Disorders Associated with Extrapyramidal Symptoms". Movement Disorders in Childhood. pp. 164–204. doi:10.1016/B978-0-7506-9852-8.00015-1. ISBN   978-0-7506-9852-8.
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