Metabolic Laboratory, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
FEBS Lett. 2012 Oct 19;586(20):3653-7. doi: 10.1016/j.febslet.2012.08.020. Epub 2012 Aug 29.
Low plasma homoarginine has emerged as a risk marker for cardiovascular disease. We exploited cells of a patient with a rare inborn error of metabolism to explore potential pathways of homoarginine synthesis, using stable isotopes and mass spectrometry. Control lymphoblasts, as opposed to lymphoblasts from an arginine:glycine amidinotransferase (AGAT)-deficient patient, were able to synthesize homoarginine from arginine and lysine. In contrast, in a patient with a deficiency of the urea cycle enzyme argininosuccinate synthase, plasma homoarginine was not decreased. We conclude that promiscuous activity of AGAT, a key enzyme in creatine synthesis, plays a pivotal role in homoarginine synthesis.
血浆同型瓜氨酸水平降低已成为心血管疾病的一个风险标志物。我们利用一名患有罕见先天性代谢缺陷疾病患者的细胞，通过使用稳定同位素和质谱分析法，来探索同型瓜氨酸合成的潜在途径。与精氨酸-甘氨酸 amidinotransferase (AGAT) 缺乏症患者的淋巴细胞不同，对照淋巴细胞能够从精氨酸和赖氨酸合成同型瓜氨酸。相比之下，在缺乏尿素循环酶精氨酸代琥珀酸合成酶的患者中，血浆同型瓜氨酸并没有减少。我们的结论是，作为肌酸合成关键酶的 AGAT 的混杂活性在同型瓜氨酸合成中起着关键作用。
