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 (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.

History

Creatine was first identified in 1832 when Michel Eugène Chevreul isolated it from the basified water-extract of skeletal muscle. He later named the crystallized precipitate after the Greek word for meat, κρέας (''kreas''). In 1928, creatine was shown to exist in equilibrium with creatinine. Studies in the 1920s showed that consumption of large amounts of creatine did not result in its excretion. This result pointed to the ability of the body to store creatine, which in turn suggested its use as a dietary supplement.

In 1912, Harvard University researchers Otto Folin and Willey Glover Denis found evidence that ingesting creatine can dramatically boost the creatine content of the muscle. In the late 1920s, after finding that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, scientists discovered ''phosphocreatine'' (creatine phosphate), and determined that creatine is a key player in the metabolism of skeletal muscle. The substance creatine is naturally formed in vertebrates.

The discovery of phosphocreatine was reported in 1927. In the 1960s, creatine kinase (CK) was shown to phosphorylate ADP using phosphocreatine (PCr) to generate ATP. It follows that ATP, not PCr is directly consumed in muscle contraction. CK uses creatine to "buffer" the ATP/ADP ratio.

While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the 1992 Olympics in Barcelona. An August 7, 1992 article in ''The Times'' reported that Linford Christie, the gold medal winner at 100 meters, had used creatine before the Olympics. An article in ''Bodybuilding Monthly'' named Sally Gunnell, who was the gold medalist in the 400-meter hurdles, as another creatine user. In addition, ''The Times'' also noted that 100 meter hurdler Colin Jackson began taking creatine before the Olympics.

left, Phosphocreatine relays phosphate to ADP.
At the time, low-potency creatine supplements were available in Britain, but creatine supplements designed for strength enhancement were not commercially available until 1993 when a company called Experimental and Applied Sciences (EAS) introduced the compound to the sports nutrition market under the name ''Phosphagen''. Research performed thereafter demonstrated that the consumption of high glycemic carbohydrates in conjunction with creatine increases creatine muscle stores.

left, The cyclic derivative creatinine exists in equilibrium with its tautomer and with creatine.

Metabolic role

Creatine is a naturally occurring non-protein compound and the primary constituent of phosphocreatine, which is used to regenerate ATP within the cell. 95% of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, testes, and other tissues. The typical creatine content of skeletal muscle (as both creatine and phosphocreatine) is 120 mmol per kilogram of dry muscle mass, but can reach up to 160 mmol/kg through supplementation. Approximately 1–2% of intramuscular creatine is degraded per day and an individual would need about 1–3 grams of creatine per day to maintain average (unsupplemented) creatine storage. An omnivorous diet provides roughly half of this value, with the remainder synthesized in the liver and kidneys.

Creatine is not an essential nutrient. It is an amino acid derivative, naturally produced in the human body from the amino acids glycine and arginine, with an additional requirement for S-Adenosyl methionine (a derivative of methionine) to catalyze the transformation of guanidinoacetate to creatine. In the first step of the biosynthesis, the enzyme arginine:glycine amidinotransferase (AGAT
EC:2.1.4.1
mediates the reaction of glycine and arginine to form guanidinoacetate. This product is then methylated by guanidinoacetate ''N''-methyltransferase (GAMT
EC:2.1.1.2
, using ''S''-adenosyl methionine as the methyl donor. Creatine itself can be phosphorylated by creatine kinase to form phosphocreatine, which is used as an energy buffer in skeletal muscles and the brain. A cyclic form of creatine, called creatinine