ABSTRACT
Creatine and phosphocreatine play an important role in intracellular energy metabolism as a high energy buffering system through the reversible reaction catalyzed by creatine kinase in which creatine and adenosine triphosphate (ATP) form phosphocreatine and adenosine diphosphate (ADP) in the mitochondria. Approximately 95 percent of creatine is found in skeletal muscle, with the rest distributed between the CNS, liver and kidney [1]. Some 50 percent is synthesized de novo, primarily in the liver, kidney and pancreas; the rest is from dietary sources. In the biosynthesis of creatine, the rate-limiting step is the conversion of arginine and glycine to guanidinoacetate (GAA) and ornithine by arginine:glycine amidinoacetate (AGAT) in the kidney. GAA is methylated in the liver to creatine by guanidinoacetate methyltransferase (GAMT) with S-adenosylmethionine acting as the methyl donor. Creatine is transported through the blood and taken up into cells against a concentration gradient by a saturable Na and Cldependent creatine transporter (CRTR). Creatine is converted non-enzymatically to creatinine, which is excreted in the urine in amounts approximately equal to the glomerular filtration rate [2].
