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Creatine is nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to muscle and nerve cells. Creatine was identified in 1832 when Michel Eugène Chevreul discovered it as a component of skeletal muscle, which he later named creatine after the Greek word for flesh, Kreas.
Creatine by way of conversion to and from phosphocreatine is present and functions in all vertebrates, as well as some invertebrates, in conjunction with the enzyme creatine kinase. A similar system based on arginine/phosphoarginine operates in many invertebrates via the action of Arginine Kinase. The presence of this energy buffer system keeps the ATP/ADP ratio high at subcellular places where ATP is needed, which ensures that the free energy of ATP remains high and minimizes the loss of adenosine nucleotides, which would cause cellular dysfunction. Such high-energy phosphate buffers in the form of phosphocreatine or phosphoarginine are known as phosphagens. In addition, due to the presence of subcompartmentalized Creatine Kinase Isoforms at specific sites of the cell, the phosphocreatine/creatine kinase system also acts as an intracellular energy transport system from those places where ATP is generated (mitochondria and glycolysis) to those places where energy is needed and used, e.g., at the myofibrils for muscle contraction, at the sarcoplasmic reticulum (SR) for calcium pumping, and at the sites of many more biological processes that depend on ATP.
In the human body, approximately half of the daily creatine is biosynthesized mainly in the vertebrates by the use of parts from three different amino acids - arginine, glycine, and methionine. The rest is taken in by alimentary sources mainly from fresh fish and meat. Ninety-five percent of creatine is later stored in the skeletal muscles, with the rest in the brain, heart, testes, inner-ear hair cells, and other organs and cells.
The enzyme GAMT (guanidinoacetate N-methyltransferase, also known as L-arginine:glycine amidinotransferase (AGAT), EC 22.214.171.124) is a mitochondrial enzyme responsible for catalyzing the first rate-limiting step of creatine biosynthesis, and is primarily expressed in the kidneys and pancreas.
The second enzyme in the pathway (GAMT, guanidinoacetate N-methyltransferase, EC:126.96.36.199) is primarily expressed in the liver and pancreas.
Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.
Creatine use in sports as a purported performance enhancer (creatine supplement) is controversial. Creatine's effectiveness is proven, however, some people still believe it should be banned from use as a performance enhancer. However, creatine still remains a commonly-used substance.
In humans, approximately half of stored creatine originates from food (mainly from fresh meat and fish). Since vegetables do not contain creatine, vegetarians clearly show lower levels of muscle creatine which, upon creatine supplementation, rise to a level higher than in meat-eaters.
Creatine and the treatment of muscular diseases
Creatine supplementation has been, and continues to be, investigated as a possible therapeutic approach for the treatment of muscular, neurological and neuromuscular diseases (arthritis, congestive heart failure, Parkinson's disease, disuse atrophy, gyrate atrophy, McArdle's disease, Huntington's disease, miscellaneous neuromuscular diseases, mitochondrial diseases, muscular dystrophy, neuroprotection, etc.).
Two studies have indicated that creatine may be beneficial for neuromuscular disorders. First, a study demonstrated that creatine is twice as effective as the prescription drug riluzole in extending the lives of mice with the degenerative neural disease amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). The neuroprotective effects of creatine in the mouse model of ALS may be due either to an increased availability of energy to injured nerve cells or to a blocking of the chemical pathway that leads to cell death.
Second, creatine has been demonstrated to cause modest increases in strength in people with a variety of neuromuscular disorders.
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Creatine". A list of authors is available in Wikipedia.|