Creatine and guanidinoacetate content of human milk and infant formulas: implications for creatine deficiency syndromes and amino acid metabolism.

Creatine is essential for normal neural development; children with inborn errors of creatine synthesis or transport exhibit neurological symptoms such as mental retardation, speech delay and epilepsy. Creatine accretion may occur through dietary intake or de novo creatine synthesis. The objective of the present study was to determine how much creatine an infant must synthesise de novo.

Suckling rat pups accumulate creatine primarily via de novo synthesis rather than from dam milk.

During lactation, there may be a higher need for creatine replacement due to the provision of creatine to the milk. Our objectives were to: 1) quantify the creatine concentration in rat milk; 2) determine the origin of milk creatine; 3) determine the activities of the enzymes of creatine synthesis in lactating rats and pups; and 4) quantify the origin of the creatine that accumulates in rat pups. The origin of milk creatine was determined in 4 dams following the administration of (14)C-creatine by measuring the isotopic enrichment of creatine in the milk and plasma.

Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo.

A fraction of the body's creatine and creatine phosphate spontaneously degrades to creatinine, which is excreted by the kidneys. In humans, this amounts to approximately 1-2 g/day and demands a comparable rate of de novo creatine synthesis. This is a two-step process in which l-arginine:glycine amidinotransferase (AGAT) catalyzes the conversion of glycine and arginine to ornithine and guanidinoacetate (GAA); guanidinoacetate methyltransferase (GAMT) then catalyzes the S-adenosylmethionine-dependent methylation of GAA to creatine.