The maximum amount of creatine the body can store is about 0.3 gram per kilogram of body weight . The creatine content of skeletal (voluntary) muscles averages 125 millimoles per kilogram of dry matter (mmol/kg/dm) and ranges from about 60 to 160 mmol/kg/dm. Approximately 60% of muscle creatine is in the form of PCr. Human muscle seems to have an upper limit of creatine storage of 150 to 160 mmol/kg/dm. Athletes with high creatine stores don't appear to benefit from supplementation, whereas individuals with the lowest levels, such as vegetarians, have the most pronounced increases following supplementation. Without supplementation, the body can replenish muscle creatine at the rate of about 2 g/day .
Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects. Clinically, there are three distinct disorders of creatine metabolism. Deficiencies in the two synthesis enzymes can cause L-arginine:glycine amidinotransferase deficiency caused by variants in GATM and guanidinoacetate methyltransferase deficiency, caused by variants in GAMT. Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, creatine transporter defect, is caused by mutations in SLC6A8 and inherited in a X-linked manner. This condition is related to the transport of creatine into the brain.
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