Creatine Synthesis from the Amino Acids: Arginine, Glycine and Methionine
Legend: Reaction 1 (catalyzed by an enzyme named AGAT) is the rate-limiting step in creatine biosynthesis. Scientific studies have shown that AGAT activity is reduced by an overabundance of creatine-a form of biological negative feedback. This typical biochemical dynamic nonetheless, raised concerns among certain scientists that prolonged creatine supplementation might inhibit endogenous creatine synthesis for an indefinite period of time. The potential strength of such a putative inhibitory effect, however, remains to be determined in humans in response to typical supplementing regimens. See Chapter 16 of my creatine guide for greater discussion of the implications of this effect.
Finally, notice that Glycine is completely incorporated into the creatine backbone, whereas Arginine and Methionine only contribute side groups.