Phosphocreatine
Encyclopedia
Phosphocreatine, also known as creatine phosphate or PCr (Pcr), is a phosphorylated
creatine
molecule that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle
and brain
.
(Arg), glycine
(Gly), and methionine
(Met). It can be synthesized by formation of guanidinoacetate from Arg and Gly (in kidney
) followed by methylation
(S-adenosyl methionine
is required) to creatine (in liver
), and phosphorylation
by creatine kinase
(ATP
is required) to phosphocreatine (in muscle); catabolism: dehydration to form the cyclic Schiff base
creatinine
. Phosphocreatine is synthesized in the liver
and transported to the muscle cells, via the bloodstream, for storage.
The creatine phosphate shuttle
facilitates transport of high energy phosphate from mitochondria.
to form ATP
during the first 2 to 7 seconds following an intense muscular or neuronal effort. On the converse, excess ATP
can be used during a period of low effort to convert creatine
to phosphocreatine. The reversible phosphorylation of creatine (i.e., both the forward and backward reaction) is catalyzed by several creatine kinase
s. The presence of creatine kinase (CK-MB, MB for muscle/brain) in plasma
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.
and separately by Cyrus Fiske and Yellapragada Subbarow
of the Harvard Medical School
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.
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
creatine
Creatine
Creatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to all cells in the body, primarily muscle. This is achieved by increasing the formation of Adenosine triphosphate...
molecule that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
and brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
.
Chemistry
Phosphocreatine is formed from parts of three amino acids: arginineArginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
(Arg), glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
(Gly), and methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
(Met). It can be synthesized by formation of guanidinoacetate from Arg and Gly (in kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
) followed by methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
(S-adenosyl methionine
S-Adenosyl methionine
S-Adenosyl methionine is a common cosubstrate involved in methyl group transfers. SAM was first discovered in Italy by G. L. Cantoni in 1952. It is made from adenosine triphosphate and methionine by methionine adenosyltransferase . Transmethylation, transsulfuration, and aminopropylation are the...
is required) to creatine (in liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
), and phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
by creatine kinase
Creatine kinase
Creatine kinase , also known as creatine phosphokinase or phospho-creatine kinase , is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate...
(ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
is required) to phosphocreatine (in muscle); catabolism: dehydration to form the cyclic Schiff base
Schiff base
A Schiff base, named after Hugo Schiff, is a compound with a functional group that contains a carbon-nitrogen double bond with the nitrogen atom connected to an aryl or alkyl group, not hydrogen....
creatinine
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
. Phosphocreatine is synthesized in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and transported to the muscle cells, via the bloodstream, for storage.
The creatine phosphate shuttle
Creatine phosphate shuttle
The creatine phosphate shuttle facilitates transport of high energy phosphate from mitochondria. This is part of the Phosphocreatine metabolism....
facilitates transport of high energy phosphate from mitochondria.
Function
Phosphocreatine can anaerobically donate a phosphate group to ADPAdenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
to form ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
during the first 2 to 7 seconds following an intense muscular or neuronal effort. On the converse, excess ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
can be used during a period of low effort to convert creatine
Creatine
Creatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to all cells in the body, primarily muscle. This is achieved by increasing the formation of Adenosine triphosphate...
to phosphocreatine. The reversible phosphorylation of creatine (i.e., both the forward and backward reaction) is catalyzed by several creatine kinase
Creatine kinase
Creatine kinase , also known as creatine phosphokinase or phospho-creatine kinase , is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate...
s. The presence of creatine kinase (CK-MB, MB for muscle/brain) in plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
is indicative of tissue damage and is used in the diagnosis of myocardial infarction. The cell's ability to generate phosphocreatine from excess ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
during rest, as well as its use of phosphocreatine for quick regeneration of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
during intense activity, provides a spatial and temporal buffer of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
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
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
. 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 CambridgeUniversity of Cambridge
The University of Cambridge is a public research university located in Cambridge, United Kingdom. It is the second-oldest university in both the United Kingdom and the English-speaking world , and the seventh-oldest globally...
and separately by Cyrus Fiske and Yellapragada Subbarow
Yellapragada Subbarao
Yellapragada Subbarao was an Indian biochemist who discovered the function of Adenosine Triphosphate as a energy source in the cell, and made important contributions to the treatment of cancer. Most of his career was spent in the United States...
of the Harvard Medical School
Harvard Medical School
Harvard Medical School is the graduate medical school of Harvard University. It is located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts....
in 1927. A few years later David Nachmansohn
David Nachmansohn
David Nachmansohn was a German-Jewish biochemist responsible for elucidating the role of phosphocreatine in energy production in the muscles, as well as nerve stimulation by the neurotransmitter acetylcholine.-References:...
, working under Meyerhof
Otto Fritz Meyerhof
-External links:* *...
at the Kaiser Wilhelm Institute
Kaiser Wilhelm Institute
The Kaiser Wilhelm Society for the Advancement of Science was a German scientific institution established in 1911. It was implicated in Nazi science, and after the Second World War was wound up and its functions replaced by the Max Planck Society...
in Dahlem, Berlin, contributed to the understanding of the phosphocreatine's role in the cell.
External links
- Human Metabolome Database at the University of AlbertaUniversity of AlbertaThe University of Alberta is a public research university located in Edmonton, Alberta, Canada. Founded in 1908 by Alexander Cameron Rutherford, the first premier of Alberta and Henry Marshall Tory, its first president, it is widely recognized as one of the best universities in Canada...