Creatine

Creatine is nitrogenous organic acid which naturally occurs 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.

Function
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 many more biological processes which depend on ATP.

Biosynthesis
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. 95% of it 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 (NOTE: image states "GATM" which is incorrect!) (guanidinoacetate N-methyltransferase, also known as L-arginine:glycine amidinotransferase (AGAT), EC 2.1.4.1) 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:2.1.1.2) is primarily expressed in the liver and pancreas.

Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.

Controversy
Creatine use in sports as a purported performance enhancer is controversial. Though its effectiveness is not proven, many believe creatine should be banned for athletes as a performance enhancing substance, but due to the legal ingredients it still remains a commonly used substance.

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 was 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 which leads to cell death.

Secondly, creatine has been demonstrated to cause modest increases in strength in people with a variety of neuromuscular disorders.