Guanidinoacetate

Guanidinoacetate, also known as guanidinoacetic acid or glycocyamine, is a naturally occurring amidine-containing compound that serves as an immediate precursor in the body's synthesis of creatine. It is part of the creatine metabolic pathway and is found in various tissues, including the liver and kidney.

Biosynthesis of guanidinoacetate occurs mainly via arginine:glycine amidinotransferase (AGAT), which transfers the amidino group from arginine to glycine to form guanidinoacetate and ornithine. The next key step is the methylation of guanidinoacetate by guanidinoacetate methyltransferase (GAMT), using S-adenosyl-L-methionine as the methyl donor, to produce creatine and S-adenosylhomocysteine. Creatine is then phosphorylated to phosphocreatine, an energy reservoir for tissues with high and fluctuating energy demands such as muscle and brain.

Physiologically, guanidinoacetate is a central intermediate in creatine production. Its levels in plasma or urine can reflect the functional status of the creatine biosynthetic pathway. Abnormal concentrations are associated with inherited disorders of creatine metabolism: GAMT deficiency leads to elevated guanidinoacetate and reduced creatine, causing neurodevelopmental and neurological symptoms, while AGAT deficiency results in low guanidinoacetate and reduced creatine.

Clinical relevance and management focus on disorders of creatine metabolism. Diagnosis often involves measuring guanidinoacetate and creatine levels in body fluids and, in GAMT deficiency, assessing guanidinoacetate elevation alongside creatine deficiency in the brain. Treatments for GAMT deficiency typically include creatine supplementation to restore creatine stores, arginine restriction to lower guanidinoacetate production, and ornithine supplementation in some cases.