Glycineamide ribonucleotide

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Glycineamide ribonucleotide
Glycineamide ribonucleotide.svg
Names
IUPAC name
(1R)-1,4-Anhydro-1-glycinamido-D-ribitol 5-(dihydrogen phosphate)
Systematic IUPAC name
[(2R,3S,4R,5R)-5-(2-Aminoacetamido)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
Other names
Glycineamide ribotide,
GAR
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
KEGG
PubChem CID
UNII
  • InChI=1S/C7H15N2O8P/c8-1-4(10)9-7-6(12)5(11)3(17-7)2-16-18(13,14)15/h3,5-7,11-12H,1-2,8H2,(H,9,10)(H2,13,14,15)/t3-,5-,6-,7-/m1/s1 Yes check.svgY
    Key: OBQMLSFOUZUIOB-SHUUEZRQSA-N Yes check.svgY
  • C([C@@H]1[C@H]([C@H]([C@@H](O1)NC(=O)CN)O)O)OP(=O)(O)O
Properties
C7H15N2O8P
Molar mass 286.177 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Glycineamide ribonucleotide (or GAR) 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 GAR. [6]

Phosphoribosylamine (PRA) Phosphoribosylamine.svg
Phosphoribosylamine (PRA)

GAR is the product of the enzyme phosphoribosylamine—glycine ligase acting on phosphoribosylamine (PRA) to combine it with glycine in a process driven by ATP. The reaction, EC 6.3.4.13 forms an amide bond: [7]

PRA + glycine + ATP → GAR + ADP + Pi

The biosynthesis pathway next adds a formyl group from 10-formyltetrahydrofolate to GAR, catalysed by phosphoribosylglycinamide formyltransferase in reaction EC 2.1.2.2 and producing formylglycinamide ribotide (FGAR): [7]

GAR + 10-formyltetrahydrofolate → FGAR + tetrahydrofolate

See also

Related Research Articles

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

Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient for humans and animals. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thiamine are required for some metabolic reactions, including the breakdown of glucose and amino acids.

<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.

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">Formylation</span>

Formylation refers to any chemical processes in which a compound is functionalized with a formyl group (-CH=O). In organic chemistry, the term is most commonly used with regards to aromatic compounds. In biochemistry the reaction is catalysed by enzymes such as formyltransferases.

<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:

Phosphoribosylformylglycinamidine cyclo-ligase 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.

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

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. The vitamins thiamine and cobalamin also contain fragments derived from PRA.

<span class="mw-page-title-main">Phosphoribosyl-N-formylglycineamide</span> 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.

<span class="mw-page-title-main">Phosphoribosylaminoimidazole carboxylase</span> Enzyme involved in purine synthesis

The enzyme Phosphoribosylaminoimidazole carboxylase, or AIR carboxylase (EC 4.1.1.21) is 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:

In enzymology, a 5-(carboxyamino)imidazole ribonucleotide mutase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Phosphoribosylamine—glycine ligase</span>

Phosphoribosylamine—glycine ligase, also known as glycinamide ribonucleotide synthetase (GARS), (EC 6.3.4.13 ) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Phosphoribosylaminoimidazolesuccinocarboxamide synthase</span> Class of enzymes

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

<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.

<span class="mw-page-title-main">5′-Phosphoribosylformylglycinamidine</span> 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.

<span class="mw-page-title-main">Phosphoribosylglycinamide formyltransferase</span>

Phosphoribosylglycinamide formyltransferase (EC 2.1.2.2, 2-amino-N-ribosylacetamide 5'-phosphate transformylase, GAR formyltransferase, GAR transformylase, glycinamide ribonucleotide transformylase, GAR TFase, 5,10-methenyltetrahydrofolate:2-amino-N-ribosylacetamide ribonucleotide transformylase) is an enzyme with systematic name 10-formyltetrahydrofolate:5'-phosphoribosylglycinamide N-formyltransferase. This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">Thiazole synthase</span>

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

<span class="mw-page-title-main">Phosphomethylpyrimidine synthase</span>

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

Dehydroglycine is the organic compound with the formula HNCHCO2H. This rarely observed species is invoked as the product of oxidation (dehydrogenation) of glycine by glycine oxidase (ThiO), which is a step in the biosynthesis of thiamin. It is also invoked as a product of the radical SAM-induced fragmentation of tyrosine. It is an imino acid.

<span class="mw-page-title-main">4-Amino-5-hydroxymethyl-2-methylpyrimidine</span> 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. 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. 1 2 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.