Phosphocreatine

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Phosphocreatine
Phosphocreatine.svg
Phosphocreatine-3D-balls.png
Names
IUPAC name
N-Methyl-N-(phosphonocarbamimidoyl)glycine
Other names
Creatine phosphate; phosphorylcreatine; creatine-P; phosphagen; fosfocreatine
Identifiers
3D model (JSmol)
AbbreviationsPCr
1797096
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.585 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 200-643-9
KEGG
PubChem CID
UNII
  • InChI=1S/C4H10N3O5P/c1-7(2-3(8)9)4(5)6-13(10,11)12/h2H2,1H3,(H,8,9)(H4,5,6,10,11,12) X mark.svgN
    Key: DRBBFCLWYRJSJZ-UHFFFAOYSA-N X mark.svgN
  • InChI=1/C4H10N3O5P/c1-7(2-3(8)9)4(5)6-13(10,11)12/h2H2,1H3,(H,8,9)(H4,5,6,10,11,12)
    Key: DRBBFCLWYRJSJZ-UHFFFAOYAF
  • OC(CN(C)C(N)=NP(O)(O)=O)=O
  • CN(CC(=O)O)C(=N)NP(=O)(O)O
Properties
C4H10N3O5P
Molar mass 211.114 g·mol−1
Pharmacology
C01EB06 ( WHO )
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H315, H319, H335
P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Phosphocreatine, also known as creatine phosphate (CP) or PCr (Pcr), is a phosphorylated form of creatine that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle, myocardium and the brain to recycle adenosine triphosphate, the energy currency of the cell.

Contents

Chemistry

In the kidneys, the enzyme AGAT catalyzes the conversion of two amino acids — arginine and glycine — into guanidinoacetate (also called glycocyamine or GAA), which is then transported in the blood to the liver. A methyl group is added to GAA from the amino acid methionine by the enzyme GAMT, forming non-phosphorylated creatine. This is then released into the blood by the liver where it travels mainly to the muscle cells (95% of the body's creatine is in muscles), and to a lesser extent the brain, heart, and pancreas. Once inside the cells it is transformed into phosphocreatine by the enzyme complex creatine kinase.

Phosphocreatine is able to donate its phosphate group to convert adenosine diphosphate (ADP) into adenosine triphosphate (ATP). This process is an important component of all vertebrates' bioenergetic systems. For instance, while the human body only produces 250 g of ATP daily, it recycles its entire body weight in ATP each day through creatine phosphate.

Phosphocreatine can be broken down into creatinine, which is then excreted in the urine. A 70 kg man contains around 120 g of creatine, with 40% being the unphosphorylated form and 60% as creatine phosphate. Of that amount, 1–2% is broken down and excreted each day as creatinine.

Phosphocreatine is used intravenously in hospitals in some parts of the world for cardiovascular problems under the name Neoton, and also used by some professional athletes, as it is not a controlled substance.

Function

Phosphocreatine can anaerobically donate a phosphate group to ADP to form ATP during the first five to eight seconds of a maximal muscular effort. [ citation needed ] Conversely, excess ATP can be used during a period of low effort to convert creatine back to phosphocreatine.

The reversible phosphorylation of creatine (i.e., both the forward and backward reaction) is catalyzed by several creatine kinases. The presence of creatine kinase (CK-MB, creatine kinase myocardial band) in blood plasma is indicative of tissue damage and is used in the diagnosis of myocardial infarction. [1]

The cell's ability to generate phosphocreatine from excess ATP during rest, as well as its use of phosphocreatine for quick regeneration of ATP during intense activity, provides a spatial and temporal buffer of ATP concentration. In other words, phosphocreatine acts as high-energy reserve in a coupled reaction; the energy given off from donating the phosphate group is used to regenerate the other compound - in this case, ATP. Phosphocreatine plays a particularly important role in tissues that have high, fluctuating energy demands such as muscle and brain.

History

The discovery of phosphocreatine [2] [3] was reported by Grace and Philip Eggleton of the University of Cambridge [4] and separately by Cyrus Fiske and Yellapragada Subbarow of the Harvard Medical School [5] in 1927. A few years later David Nachmansohn, working under Meyerhof at the Kaiser Wilhelm Institute in Dahlem, Berlin, contributed to the understanding of the phosphocreatine's role in the cell. [3]

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">Kinase</span> Enzyme catalyzing transfer of phosphate groups onto specific substrates

In biochemistry, a kinase is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule donates a phosphate group to the substrate molecule. As a result, kinase produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group. These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis.

<span class="mw-page-title-main">Creatinine</span> Breakdown product of creatine phosphate

Creatinine is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body.

<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-.

Phosphagens, also known as macroergic compounds, are high energy storage compounds, also known as high-energy phosphate compounds, chiefly found in muscular tissue in animals. They allow a high-energy phosphate pool to be maintained in a concentration range, which, if it all were adenosine triphosphate (ATP), would create problems due to the ATP-consuming reactions in these tissues. As muscle tissues can have sudden demands for much energy, these compounds can maintain a reserve of high-energy phosphates that can be used as needed, to provide the energy that could not be immediately supplied by glycolysis or oxidative phosphorylation. Phosphagens supply immediate but limited energy.

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

Creatine is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. It exists in various tautomers in solutions. Creatine is found in vertebrates, where it facilitates recycling of adenosine triphosphate (ATP), primarily in muscle and brain tissue. Recycling is achieved by converting adenosine diphosphate (ADP) back to ATP via donation of phosphate groups. Creatine also acts as a buffer.

<span class="mw-page-title-main">Creatine kinase</span> Class of enzymes

Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create phosphocreatine (PCr) and adenosine diphosphate (ADP). This CK enzyme reaction is reversible and thus ATP can be generated from PCr and ADP.

<span class="mw-page-title-main">ATP hydrolysis</span> Catabolism of ATP into ADP

ATP hydrolysis is the catabolic reaction process by which chemical energy that has been stored in the high-energy phosphoanhydride bonds in adenosine triphosphate (ATP) is released after splitting these bonds, for example in muscles, by producing work in the form of mechanical energy. The product is adenosine diphosphate (ADP) and an inorganic phosphate (Pi). ADP can be further hydrolyzed to give energy, adenosine monophosphate (AMP), and another inorganic phosphate (Pi). ATP hydrolysis is the final link between the energy derived from food or sunlight and useful work such as muscle contraction, the establishment of electrochemical gradients across membranes, and biosynthetic processes necessary to maintain life.

Substrate-level phosphorylation is a metabolism reaction that results in the production of ATP or GTP supported by the energy released from another high-energy bond that leads to phosphorylation of ADP or GDP to ATP or GTP (note that the reaction catalyzed by creatine kinase is not considered as "substrate-level phosphorylation"). This process uses some of the released chemical energy, the Gibbs free energy, to transfer a phosphoryl (PO3) group to ADP or GDP. Occurs in glycolysis and in the citric acid cycle.

<span class="mw-page-title-main">Succinyl coenzyme A synthetase</span> Class of enzymes

Succinyl coenzyme A synthetase is an enzyme that catalyzes the reversible reaction of succinyl-CoA to succinate. The enzyme facilitates the coupling of this reaction to the formation of a nucleoside triphosphate molecule from an inorganic phosphate molecule and a nucleoside diphosphate molecule. It plays a key role as one of the catalysts involved in the citric acid cycle, a central pathway in cellular metabolism, and it is located within the mitochondrial matrix of a cell.

Translocase is a general term for a protein that assists in moving another molecule, usually across a cell membrane. These enzymes catalyze the movement of ions or molecules across membranes or their separation within membranes. The reaction is designated as a transfer from “side 1” to “side 2” because the designations “in” and “out”, which had previously been used, can be ambiguous. Translocases are the most common secretion system in Gram positive bacteria.

<span class="mw-page-title-main">Bioenergetic systems</span> Metabolic processes for energy production

Bioenergetic systems are metabolic processes that relate to the flow of energy in living organisms. Those processes convert energy into adenosine triphosphate (ATP), which is the form suitable for muscular activity. There are two main forms of synthesis of ATP: aerobic, which uses oxygen from the bloodstream, and anaerobic, which does not. Bioenergetics is the field of biology that studies bioenergetic systems.

<span class="mw-page-title-main">CKMT2</span> Protein and coding gene in humans

Creatine kinase S-type, mitochondrial is an enzyme that in humans is encoded by the CKMT2 gene.

Creatine kinase U-type, mitochondrial, also called ubiquitous mitochondrial creatine kinase (uMtCK), is in humans encoded by CKMT1A gene. CKMT1A catalyzes the reversible transfer of the γ-phosphate group of ATP to the guanidino group of Cr to yield ADP and PCr. The impairment of CKMT1A has been reported in ischaemia, cardiomyopathy, and neurodegenerative disorders. Overexpression of CKMT1A has been reported related with several tumors.

<span class="mw-page-title-main">CKM (gene)</span> Protein and coding gene in humans

Creatine kinase, muscle also known as MCK is a creatine kinase that in humans is encoded by the MCK gene.

<span class="mw-page-title-main">CKB (gene)</span> Protein and coding gene in humans

Brain-type creatine kinase also known as CK-BB is a creatine kinase that in humans is encoded by the CKB gene.

<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.

<span class="mw-page-title-main">ATP:guanido phosphotransferase family</span>

In molecular biology, the ATP:guanido phosphotransferase family is a family of structurally and functionally related enzymes, that reversibly catalyse the transfer of phosphate between ATP and various phosphagens. The enzymes belonging to this family include:

<span class="mw-page-title-main">Creatine phosphate shuttle</span> Intracellular energy shuttle in muscles

The creatine phosphate shuttle is an intracellular energy shuttle which facilitates transport of high energy phosphate from muscle cell mitochondria to myofibrils. This is part of phosphocreatine metabolism. In mitochondria, Adenosine triphosphate (ATP) levels are very high as a result of glycolysis, TCA cycle, oxidative phosphorylation processes, whereas creatine phosphate levels are low. This makes conversion of creatine to phosphocreatine a highly favored reaction. Phosphocreatine is a very-high-energy compound. It then diffuses from mitochondria to myofibrils.

References

  1. Schlattner U, Tokarska-Schlattner M, Wallimann T (2006). "Mitochondrial creatine kinase in human health and disease". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1762 (2): 164–180. doi: 10.1016/j.bbadis.2005.09.004 . PMID   16236486.
  2. Saks, Valdur (2007). Molecular system bioenergetics: energy for life . Weinheim: Wiley-VCH. p.  2. ISBN   978-3-527-31787-5.
  3. 1 2 Ochoa, Severo (1989). Sherman, E. J.; National Academy of Sciences (eds.). David Nachmansohn. Biographical Memoirs. Vol. 58. National Academies Press. pp. 357–404. ISBN   978-0-309-03938-3.
  4. Eggleton, Philip; Eggleton, Grace Palmer (1927). "The inorganic phosphate and a labile form of organic phosphate in the gastrocnemius of the frog". Biochemical Journal. 21 (1): 190–195. doi:10.1042/bj0210190. PMC   1251888 . PMID   16743804.
  5. Fiske, Cyrus H.; Subbarao, Yellapragada (1927). "The nature of the 'inorganic phosphate' in voluntary muscle". Science. 65 (1686): 401–403. Bibcode:1927Sci....65..401F. doi:10.1126/science.65.1686.401. PMID   17807679.