Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo
Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo
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DOI：
10.1152/ajprenal.00356.2007
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发表时间：
2007-12-01
影响因子：
4.2
通讯作者：
Brosnan, John T.
中科院分区：
文献类型：
--
作者：
Edison, Erica E.;Brosnan, Margaret E.;Brosnan, John T.
人体中的一小部分肌酸和肌酸磷酸会自发降解为肌酸，由肾脏排泄。在人类中，这相当于每天1-2克，需要相当的从头合成肌酸的速度。这是一个分两步进行的过程：L-精氨酸：甘氨酸氨基转移酶催化甘氨酸和精氨酸转化为鸟氨酸和乙酸胍；乙酸胍甲基转移酶催化S-腺苷蛋氨酸依赖的甲基化反应生成肌酸。AGAT在肾脏中被发现，GAMT在肝脏中被发现，这意味着GAA从肾脏到肝脏的器官间运动。我们研究了这种代谢物在大鼠和人类体内的肾脏产生情况。对照组大鼠动脉血浆[GAA]为5.9mU，肾静脉血浆[GAA]为10.9mU，肾动静脉(A-V)差为-5.0mU。饲喂0.4%肌酸的大鼠肾脏AGAT活性和mRNA降低，动脉血[GAA]为1.5mU，肾脏A-V差为-0.9mM。在人类，动脉血浆[GAA]为2.4mU，肾A-V差为-1.1mM。这些研究首次证明，GAA在体内由大鼠和人肾同时产生。
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 similar 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 mu M in arterial plasma and 10.9 mu M in renal venous plasma for a renal arteriovenous (A-V) difference of -5.0 mu M. 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 mu M, and a decreased renal A-V difference for GAA of -0.9 mu M. In humans, [GAA] was 2.4 mu M in arterial plasma, with a renal A-V difference of -1.1 mu M. These studies show, for the first time, that GAA is produced by both rat and human kidneys in vivo.