Biosynthesis
Creatine is naturally produced in the human body from amino acids primarily in the kidney and liver. It is transported in the blood for use by muscles. Approximately 95% of the human body's total creatine is located in skeletal muscle.
Creatine is not an essential nutrient, as it is manufactured in the human body from L-arginine, glycine, and L-methionine.
In humans and animals, approximately half of stored creatine originates from food (about 1 g/day, mainly from meat). A study, involving 18 vegetarians and 24 non-vegetarians, on the effect of creatine in vegetarians showed that total creatine was significantly lower than in non-vegetarians. Since vegetables do not represent the primary source of creatine, vegetarians can be expected to show lower levels of directly derived muscle creatine. However, the subjects happened to show the same levels after using supplements. Given the fact that creatine can be synthesized from the above mentioned amino acids, protein sources rich in these amino acids can be expected to provide adequate capability of native biosynthesis in the human body.
The enzyme GATM (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.
Read more about this topic: Creatine