Figure 1

Creatine is an amino acid derivative involved with cellular energy production. In the form of energetically charged phosphocreatine (PCr), its primary function is to provide the phosphate group for regeneration of ATP from ADP in tissues of high and fluctuating energy demands. Human adults obtain approximately half of their daily requirement for creatine from a diet containing fresh fish, meat, and other animal products. The remainder is synthesized endogenously from arginine, glycine and methionine (methyl donor for GAMT reaction). This is a two-step process involving arginine:glycine aminotransferase (AGAT), principally in the kidney, producing guanidinoacetate (GAA), followed by hepatic guanidinoacetate methyltransferase (GAMT) activity producing creatine. Once synthesized, creatine is released from the liver into the circulation and taken up by most tissues, particularly muscle, by means of the creatine transporter. Inside the tissues a proportion of the creatine is phosphorylated to PCr, via the action of creatine kinase (CK). One important aspect of creatine biosynthesis is that the daily utilization of methyl groups on the GAMT reaction roughly equals the total daily intake of ‘labile’ methyl groups (methionine + choline) in an average diet. Thus, if methionine and choline levels are reduced, then endogenous creatine biosynthesis, responsible for half of our daily requirement for creatine, may be critically reduced.