Takeda M
Department of Medicine, Juntendo University School of Medicine.
Nihon Jinzo Gakkai Shi. 1990 Feb;32(2):117-26.
Guanidinoacetic acid (GAA), a precursor of creatine, is an essential substrate for muscle energy metabolism. GAA is formed from arginine and glycine by glycine-amidinotransferase (GAT) mainly in the kidney. But mechanism of GAA synthesis in the kidney has not been defined. The author isolated renal tubules from rats and incubated them with various substrates. GAA was separated by HPLC and measured fluorometrically after reacting with 9, 10-phenanthrenequinone. The following results were obtained: 1. GAA synthesis in the isolated renal tubules was recognized without addition of any substrate. 2. A remarkable increase of the amount of GAA was observed in the presence of glycine and several amidine donors, such as arginine and canavanine. 3. The amount of GAA tended to increase until 3 hours. 4. D.L-norvaline and ornithine suppressed GAA synthesis in renal tubules. 5. Methionine suppressed GAA synthesis. 6. Creatine suppressed GAA synthesis. Negative feedback control of GAA synthesis by creatine was recognized in vitro. 7. GAA synthetic activity was not recognized after the addition of hydroxyurea, citrulline and argininosuccinic acid in the medium. 8. Low concentrations of methylguanidine and guanidinosuccinic acid decreased the amount of GAA. Concentrations used in the experiment were similar to those in uremic serum.
胍基乙酸（GAA）是肌酸的前体，是肌肉能量代谢的必需底物。GAA主要在肾脏中由精氨酸和甘氨酸通过甘氨酸脒基转移酶（GAT）形成。但肾脏中GAA合成的机制尚未明确。作者从大鼠中分离出肾小管，并用各种底物对其进行孵育。GAA通过高效液相色谱法分离，并在与9,10-菲醌反应后进行荧光测定。得到以下结果：1. 在不添加任何底物的情况下，可观察到分离的肾小管中有GAA合成。2. 在甘氨酸和几种脒基供体（如精氨酸和刀豆氨酸）存在的情况下，观察到GAA的量显著增加。3. GAA的量在3小时前趋于增加。4. D.L-正缬氨酸和鸟氨酸抑制肾小管中GAA的合成。5. 蛋氨酸抑制GAA的合成。6. 肌酸抑制GAA的合成。在体外证实了肌酸对GAA合成的负反馈控制。7. 在培养基中添加羟基脲、瓜氨酸和精氨琥珀酸后，未观察到GAA合成活性。8. 低浓度的甲基胍和胍基琥珀酸降低了GAA的量。实验中使用的浓度与尿毒症血清中的浓度相似。
