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This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/F1799    most recent 00356.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Edison, E. E. Articles by Brosnan, J. T. Search for Related Content PubMed PubMed Citation Articles by Edison, E. E. Articles by Brosnan, J. T.

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

¹Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada; ²Department of Endocrinology, Carl T. Hayden Veterans Affairs Medical Center, Phoenix; and ³Center of Metabolic Biology, Department of Kinesiology, Arizona State University, Tempe, Arizona

Submitted 30 July 2007 ; accepted in final form 3 October 2007

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 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. AGAT is found in the kidney and GAMT in the liver, which implies an interorgan movement of GAA from the kidney to the liver. We studied the renal production of this metabolite in both rats and humans. In control rats, [GAA] was 5.9 µM in arterial plasma and 10.9 µM in renal venous plasma for a renal arteriovenous (A-V) difference of –5.0 µM. In the rat, infusion of arginine or citrulline markedly increased renal GAA production but infusion of glycine did not. Rats fed 0.4% creatine in their diet had decreased renal AGAT activity and mRNA, an arterial plasma [GAA] of 1.5 µM, and a decreased renal A-V difference for GAA of –0.9 µM. In humans, [GAA] was 2.4 µM in arterial plasma, with a renal A-V difference of –1.1 µM. These studies show, for the first time, that GAA is produced by both rat and human kidneys in vivo.

L-arginine:glycine amidinotransferase; transamidinase; amino acid metabolism