Phosphocreatine
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Phosphocreatine, also known as creatine phosphate (CP) or PCr (Pcr), is a
phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...
form of
creatine Creatine ( or ) is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. It exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate ( ...
that serves as a rapidly mobilizable reserve of high-energy phosphates in
skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
,
myocardium Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...
and the
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
to recycle
adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of ...
, the energy currency of the cell.


Chemistry

In the kidneys, the enzyme AGAT catalyzes the conversion of two amino acids —
arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
and
glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...
— into
guanidinoacetate Glycocyamine (or guanidinoacetate) is a metabolite of glycine in which the amino group has been converted into a guanidine by guanylation (transfer of a guanidine group from arginine). In vertebrate organism it is then transformed into creatine by ...
(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 Guanidinoacetate N-methyltransferase () is an enzyme that catalyzes the chemical reaction and is encoded by gene ''GAMT'' located on chromosome 19p13.3. :S-adenosyl-L-methionine + guanidinoacetate \rightleftharpoons S-adenosyl-L-homocysteine + ...
, 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 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 phosp ...
. Phosphocreatine is able to donate its phosphate group to convert
adenosine diphosphate 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 backbon ...
(ADP) into
adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of ...
(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 Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an import ...
, 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. Conversely, excess ATP can be used during a period of low effort to convert
creatine Creatine ( or ) is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. It exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate ( ...
back to phosphocreatine. The reversible phosphorylation of creatine (i.e., both the forward and backward reaction) is catalyzed by several
creatine kinase 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 phosp ...
s. The presence of creatine kinase (
CK-MB The CPK-MB test (creatine phosphokinase-MB), also known as CK-MB test, is a cardiac marker used to assist diagnoses of an acute myocardial infarction, myocardial ischemia, or myocarditis. It measures the blood level of CK-MB (creatine kinase myoca ...
, creatine kinase myocardial band) in
blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...
is indicative of tissue damage and is used in the diagnosis of myocardial infarction. 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 was reported by Grace and Philip Eggleton of the
University of Cambridge , mottoeng = Literal: From here, light and sacred draughts. Non literal: From this place, we gain enlightenment and precious knowledge. , established = , other_name = The Chancellor, Masters and Schola ...
and separately by
Cyrus Fiske Cyrus (Persian: کوروش) is a male given name. It is the given name of a number of Persian kings. Most notably it refers to Cyrus the Great ( BC). Cyrus is also the name of Cyrus I of Anshan ( BC), King of Persia and the grandfather of Cyrus t ...
and
Yellapragada Subbarow Yellapragada Subba Rao (12 January 1895 – 8 August 1948) was a pioneering Indian biochemist who discovered the function of adenosine triphosphate (ATP) as an energy source in the cell, developed methotrexate for the treatment of cancer a ...
of the
Harvard Medical School Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
in 1927. A few years later
David Nachmansohn David Nachmansohn (17 March 1899 – 2 November 1983) was a German-Jewish biochemist responsible for elucidating the role of phosphocreatine in energy production in the muscles, and the role of the neurotransmitter acetylcholine in nerve stimula ...
, working under Meyerhof at the
Kaiser Wilhelm Institute The Kaiser Wilhelm Society for the Advancement of Science (German: ''Kaiser-Wilhelm-Gesellschaft zur Förderung der Wissenschaften'') was a German scientific institution established in the German Empire in 1911. Its functions were taken over by ...
in Dahlem, Berlin, contributed to the understanding of the phosphocreatine's role in the cell.


References


External links


Human Metabolome Database
at the
University of Alberta The University of Alberta, also known as U of A or UAlberta, is a public research university located in Edmonton, Alberta, Canada. It was founded in 1908 by Alexander Cameron Rutherford,"A Gentleman of Strathcona – Alexander Cameron Rutherfor ...
{{Amino acid metabolism intermediates Carboxylic acids Guanidines Phosphoramidates