Phosphoribosylamine

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Phosphoribosylamine
Phosphoribosylamine.svg
Names
Other names
PRA
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
MeSH Phosphoribosylamine
PubChem CID
  • InChI=1S/C5H12NO7P/c6-5-4(8)3(7)2(13-5)1-12-14(9,10)11/h2-5,7-8H,1,6H2,(H2,9,10,11)/t2-,3-,4-,5?/m1/s1 Yes check.svgY
    Key: SKCBPEVYGOQGJN-SOOFDHNKSA-N Yes check.svgY
  • C([C@@H]1[C@H]([C@H](C(O1)N)O)O)OP(=O)(O)O
Properties
C5H12NO7P
Molar mass 229.125 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Phosphoribosylamine (PRA) is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. [1] [2] [3] The vitamins thiamine [4] and cobalamin [5] also contain fragments derived from PRA. [6]

Phosphoribosyl pyrophosphate (PRPP) Phosphoribosyl pyrophosphate.svg
Phosphoribosyl pyrophosphate (PRPP)

It is the product of the enzyme amidophosphoribosyltransferase which attaches ammonia from glutamine to phosphoribosyl pyrophosphate (PRPP) at its anomeric carbon: [2]

PRPP + glutaminePRA + glutamate + PPi

The biosynthesis pathway next combines PRA with glycine in a process driven by ATP giving glycineamide ribonucleotide (GAR). The enzyme phosphoribosylamine—glycine ligase catalyses the reaction forming an amide bond: [7]

PRA + glycine + ATP → GAR + ADP + Pi

See also

Related Research Articles

Nucleotide Biological molecules that form the building blocks of nucleic acids

Nucleotides are organic molecules consisting of a nucleoside 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.

Thiamine Chemical compound

Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, which cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Food sources of thiamine include whole grains, legumes, and some meats and fish. Grain processing removes much of the thiamine content, so in many countries cereals and flours are enriched with thiamine. Supplements and medications are available to treat and prevent thiamine deficiency and disorders that result from it, including beriberi and Wernicke encephalopathy. Other uses include the treatment of maple syrup urine disease and Leigh syndrome. They are typically taken by mouth, but may also be given by intravenous or intramuscular injection.

Ribonucleotide 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.

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.

Formylation

In biochemistry, the addition of a formyl functional group is termed formylation. A formyl functional group consists of a carbonyl bonded to hydrogen. When attached to an R group, a formyl group is called an aldehyde.

Phosphoribosyl pyrophosphate Chemical compound

Phosphoribosyl pyrophosphate (PRPP) is a pentose phosphate and a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate. Hence it is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments derived from PRPP. It is formed from ribose 5-phosphate (R5P) by the enzyme ribose-phosphate diphosphokinase in reaction:

Ribose 5-phosphate Chemical compound

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.

AIR synthetase is the fifth enzyme in the de novo synthesis of purine nucleotides. It catalyzes the reaction to form 5-aminoimidazole ribotide (AIR) from formylglycinamidine-ribonucleotide FGAM. This reaction closes the ring and produces a 5-membered imidazole ring of the purine nucleus (AIR):

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

Amidophosphoribosyltransferase

Amidophosphoribosyltransferase (ATase), also known as glutamine phosphoribosylpyrophosphate amidotransferase (GPAT), is an enzyme responsible for catalyzing the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) into 5-phosphoribosyl-1-amine (PRA), using the amine group from a glutamine side-chain. This is the committing step in de novo purine synthesis. In humans it is encoded by the PPAT gene. ATase is a member of the purine/pyrimidine phosphoribosyltransferase family.

Phosphoribosyl-N-formylglycineamide Chemical compound

Phosphoribosyl-N-formylglycineamide 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 FGAR.

Phosphoribosylaminoimidazole carboxylase

Phosphoribosylaminoimidazole carboxylase (or AIR carboxylase) is an enzyme involved in nucleotide biosynthesis and in particular in purine biosynthesis. It catalyzes the conversion of 5'-phosphoribosyl-5-aminoimidazole ("AIR") into 5'-phosphoribosyl-4-carboxy-5-aminoimidazole ("CAIR") as described in the reaction:

Phosphoribosylamine—glycine ligase

In enzymology, phosphoribosylamine-glycine ligase, also known as glycinamide ribonucleotide synthetase (GARS), (EC 6.3.4.13) is an enzyme that catalyzes the chemical reaction

Phosphoribosylaminoimidazolesuccinocarboxamide synthase

In molecular biology, the protein domain SAICAR synthase is an enzyme which catalyses a reaction to create SAICAR. In enzymology, this enzyme is also known as phosphoribosylaminoimidazolesuccinocarboxamide synthase. It is an enzyme that catalyzes the chemical reaction

5-Aminoimidazole ribotide 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.

5-Phosphoribosylformylglycinamidine Chemical compound

5'-Phosphoribosylformylglycinamidine 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 FGAM.

Glycineamide ribonucleotide Chemical compound

Glycineamide ribonucleotide 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 GAR.

Thiazole synthase

Thiazole synthase (EC 2.8.1.10, thiG (gene)) is an enzyme with systematic name 1-deoxy-D-xylulose 5-phosphate:thiol sulfurtransferase. This enzyme catalyses the following chemical reaction

Phosphomethylpyrimidine synthase

Phosphomethylpyrimidine synthase is an enzyme with systematic name 5-amino-1-(5-phospho-D-ribosyl)imidazole formate-lyase . This enzyme catalyses the following chemical reaction

4-Amino-5-hydroxymethyl-2-methylpyrimidine Chemical compound

Within the field of biochemistry, 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) also known as toxopyrimidine together with its mono phosphate (HMP-P) and pyrophosphate (HMP-PP) esters are biogenetic precursors to the important biochemical cofactor thiamine pyrophosphate (TPP), a derivative of thiamine (vitamin B1).

References

  1. R. Caspi (2009-01-13). "Pathway: 5-aminoimidazole ribonucleotide biosynthesis I". MetaCyc Metabolic Pathway Database. Retrieved 2022-02-02.
  2. 1 2 Zhang, Y.; Morar, M.; Ealick, S.E. (2008). "Structural biology of the purine biosynthetic pathway". Cellular and Molecular Life Sciences. 65: 3699–3724. doi:10.1007/s00018-008-8295-8. PMC   2596281 . PMID   18712276.
  3. Gupta, Rani; Gupta, Namita (2021). "Nucleotide Biosynthesis and Regulation". Fundamentals of Bacterial Physiology and Metabolism. pp. 525–554. doi:10.1007/978-981-16-0723-3_19. ISBN   978-981-16-0722-6. S2CID   234897784.
  4. Chatterjee, Abhishek; Hazra, Amrita B.; Abdelwahed, Sameh; Hilmey, David G.; Begley, Tadhg P. (2010). "A "Radical Dance" in Thiamin Biosynthesis: Mechanistic Analysis of the Bacterial Hydroxymethylpyrimidine Phosphate Synthase". Angewandte Chemie International Edition. 49 (46): 8653–8656. doi:10.1002/anie.201003419. PMC   3147014 . PMID   20886485.
  5. R. Caspi (2019-09-23). "Pathway: 5-hydroxybenzimidazole biosynthesis (anaerobic)". MetaCyc Metabolic Pathway Database. Retrieved 2022-02-10.
  6. Mehta, Angad P.; Abdelwahed, Sameh H.; Fenwick, Michael K.; Hazra, Amrita B.; Taga, Michiko E.; Zhang, Yang; Ealick, Steven E.; Begley, Tadhg P. (2015). "Anaerobic 5-Hydroxybenzimidazole Formation from Aminoimidazole Ribotide: An Unanticipated Intersection of Thiamin and Vitamin B12 Biosynthesis". Journal of the American Chemical Society. 137 (33): 10444–10447. doi:10.1021/jacs.5b03576. PMC   4753784 . PMID   26237670.
  7. Welin, Martin; Grossmann, Jörg Günter; Flodin, Susanne; Nyman, Tomas; Stenmark, Pål; Trésaugues, Lionel; Kotenyova, Tetyana; Johansson, Ida; Nordlund, Pär; Lehtiö, Lari (2010). "Structural studies of tri-functional human GART". Nucleic Acids Research. 38 (20): 7308–7319. doi:10.1093/nar/gkq595. PMC   2978367 . PMID   20631005.