Adenylosuccinate

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Adenylosuccinate
Aspartyl adenylate.svg
Names
IUPAC name
(2S)-2-[[9-[(2R,3R,4S,5R)-3,4-Dihydroxy-5-(phosphonooxymethyl)oxolan-2-yl]purin-6-yl]amino]butanedioic acid
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
MeSH Adenylosuccinate
PubChem CID
UNII
  • InChI=1S/C14H18N5O11P/c20-7(21)1-5(14(24)25)18-11-8-12(16-3-15-11)19(4-17-8)13-10(23)9(22)6(30-13)2-29-31(26,27)28/h3-6,9-10,13,22-23H,1-2H2,(H,20,21)(H,24,25)(H,15,16,18)(H2,26,27,28)/t5?,6-,9-,10-,13-/m1/s1 Yes check.svgY
    Key: OFBHPPMPBOJXRT-DPXQIYNJSA-N Yes check.svgY
  • InChI=1/C14H18N5O11P/c20-7(21)1-5(14(24)25)18-11-8-12(16-3-15-11)19(4-17-8)13-10(23)9(22)6(30-13)2-29-31(26,27)28/h3-6,9-10,13,22-23H,1-2H2,(H,20,21)(H,24,25)(H,15,16,18)(H2,26,27,28)/t5?,6-,9-,10-,13-/m1/s1
    Key: OFBHPPMPBOJXRT-DPXQIYNJBG
  • C1=NC2=C(C(=N1)N[C@@H](CC(=O)O)C(=O)O)N=CN2[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(O)O)O)O
Properties
C14H18N5O11P
Molar mass 463.296 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Adenylosuccinate, also known as succinyl-adenosine monophosphate (S-AMP), is an intermediate in the interconversion of purine nucleotides inosine monophosphate (IMP) and adenosine monophosphate (AMP). The enzyme adenylosuccinate synthase carries out the reaction of IMP to S-AMP in a 2 step mechanism, [1] requiring the input of energy from a phosphoanhydride bond from the hydrolysis of guanosine triphosphate (GTP) [2] first, followed by the addition of aspartate. This reaction needs Mg2+, [3] and is competitively inhibited by the subsequent product AMP [3] in a negative feedback mechanism. [4] GTP, the product of another pathway from IMP, is used instead of adenosine triphosphate (ATP) as the phosphate source. The enzyme adenylosuccinate lyase carries out the reaction removing the carbon skeleton from S-AMP attached from aspartate, forming AMP and fumarate. [4] The pathway from IMP to AMP is present across various prokaryotes and eukaryotes, and is linked to various diseases. [5] S-AMP has been observed to stimulate insulin production. [6]

See also

Related Research Articles

<span class="mw-page-title-main">Adenosine triphosphate</span> Energy-carrying molecule in living cells

Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known forms of life, it is often referred to as the "molecular unit of currency" for intracellular energy transfer.

<span class="mw-page-title-main">Nucleotide</span> Biological molecules constituting 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">Adenosine diphosphate</span> Chemical compound

Adenosine diphosphate (ADP), also known as adenosine pyrophosphate (APP), is an important organic compound in metabolism and is essential to the flow of energy in living cells. ADP consists of three important structural components: a sugar backbone attached to adenine and two phosphate groups bonded to the 5 carbon atom of ribose. The diphosphate group of ADP is attached to the 5’ carbon of the sugar backbone, while the adenine attaches to the 1’ carbon.

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

Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine. It is an ester of phosphoric acid and the nucleoside adenosine. As a substituent it takes the form of the prefix adenylyl-.

<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.

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.

Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-catalyzed processes where chemical substances absorbed as nutrients serve as enzyme substrates, with conversion by the living organism either into simpler or more complex products. Examples of biosynthetic pathways include those for the production of amino acids, lipid membrane components, and nucleotides, but also for the production of all classes of biological macromolecules, and of acetyl-coenzyme A, adenosine triphosphate, nicotinamide adenine dinucleotide and other key intermediate and transactional molecules needed for metabolism. Thus, in biosynthesis, any of an array of compounds, from simple to complex, are converted into other compounds, and so it includes both the catabolism and anabolism of complex molecules. Biosynthetic processes are often represented via charts of metabolic pathways. A particular biosynthetic pathway may be located within a single cellular organelle, while others involve enzymes that are located across an array of cellular organelles and structures.

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

Inosinic acid or inosine monophosphate (IMP) is a nucleotide. Widely used as a flavor enhancer, it is typically obtained from chicken byproducts or other meat industry waste. Inosinic acid is important in metabolism. It is the ribonucleotide of hypoxanthine and the first nucleotide formed during the synthesis of purine nucleotides. It can also be formed by the deamination of adenosine monophosphate by AMP deaminase. It can be hydrolysed to inosine.

<span class="mw-page-title-main">Adenylosuccinate lyase deficiency</span> Medical condition

Adenylosuccinate lyase deficiency is a rare autosomal recessive metabolic disorder characterized by the appearance of succinylaminoimidazolecarboxamide riboside and succinyladenosine (S-Ado) in cerebrospinal fluid, urine. These two succinylpurines are the dephosphorylated derivatives of SAICA ribotide (SAICAR) and adenylosuccinate (S-AMP), the two substrates of adenylosuccinate lyase (ADSL), which catalyzes an important reaction in the de novo pathway of purine biosynthesis. ADSL catalyzes two distinct reactions in the synthesis of purine nucleotides, both of which involve the β-elimination of fumarate to produce aminoimidazole carboxamide ribotide (AICAR) from SAICAR or adenosine monophosphate (AMP) from S-AMP.

<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.

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">GMP synthase</span>

Guanosine monophosphate synthetase, also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate.

<span class="mw-page-title-main">GMP reductase</span> Class of enzymes

GMP reductase EC 1.7.1.7 is an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of GMP into IMP.

<span class="mw-page-title-main">Adenylosuccinate lyase</span>

Adenylosuccinate lyase is an enzyme that in humans is encoded by the ADSL gene.

<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.

In enzymology, an adenosine-phosphate deaminase (EC 3.5.4.17) is an enzyme that catalyzes the chemical reaction

In enzymology, a nucleoside-triphosphate-adenylate kinase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Purine nucleotide cycle</span> Protein metabolic pathway

The Purine Nucleotide Cycle is a metabolic pathway in protein metabolism requiring the amino acids aspartate and glutamate. The cycle is used to regulate the levels of adenine nucleotides, in which ammonia and fumarate are generated. AMP converts into IMP and the byproduct ammonia. IMP converts to S-AMP (adenylosuccinate), which then converts to AMP and the byproduct fumarate. The fumarate goes on to produce ATP (energy) via oxidative phosphorylation as it enters the Krebs cycle and then the electron transport chain. Lowenstein first described this pathway and outlined its importance in processes including amino acid catabolism and regulation of flux through glycolysis and the Krebs cycle.

The gua operon is responsible for regulating the synthesis of guanosine mono phosphate (GMP), a purine nucleotide, from inosine monophosphate. It consists of two structural genes guaB (encodes for IMP dehydrogenase or and guaA apart from the promoter and operator region.

References

  1. Mehrotra, Sonali; Balaram, Hemalatha (2007-11-06). "Kinetic characterization of adenylosuccinate synthetase from the thermophilic archaea Methanocaldococcus jannaschii". Biochemistry. 46 (44): 12821–12832. doi:10.1021/bi701009y. ISSN   0006-2960. PMID   17929831.
  2. Figures 20.4 and 20.7 in Textbook of Biochemistry, with clinical correlations, Sixth Edition, Thomas M. Devlin, Ed., Wiley-Liss, Inc., New York, NY, 2006
  3. 1 2 Iancu, Cristina V.; Borza, Tudor; Fromm, Herbert J.; Honzatko, Richard B. (2002-10-25). "Feedback inhibition and product complexes of recombinant mouse muscle adenylosuccinate synthetase". The Journal of Biological Chemistry. 277 (43): 40536–40543. doi: 10.1074/jbc.M204952200 . ISSN   0021-9258. PMID   12186864.
  4. 1 2 Garrett, Reginald H.; Grisham, Charles M. (2017). Biochemistry (6th ed.). Boston, MA: Cengage Learning. pp. 927–940. ISBN   978-1-305-57720-6.
  5. Marsac, Roxane; Pinson, Benoît; Saint-Marc, Christelle; Olmedo, María; Artal-Sanz, Marta; Daignan-Fornier, Bertrand; Gomes, José-Eduardo (2019). "Purine Homeostasis Is Necessary for Developmental Timing, Germline Maintenance and Muscle Integrity in Caenorhabditis elegans". Genetics. 211 (4): 1297–1313. doi:10.1534/genetics.118.301062. ISSN   1943-2631. PMC   6456310 . PMID   30700528.
  6. Gooding, Jessica R.; Jensen, Mette V.; Dai, Xiaoqing; Wenner, Brett R.; Lu, Danhong; Arumugam, Ramamani; Ferdaoussi, Mourad; MacDonald, Patrick E.; Newgard, Christopher B. (2015-10-06). "Adenylosuccinate Is an Insulin Secretagogue Derived from Glucose-Induced Purine Metabolism". Cell Reports. 13 (1): 157–167. doi:10.1016/j.celrep.2015.08.072. ISSN   2211-1247. PMC   4598307 . PMID   26411681.