Promiscuous activity of arginine:glycine amidinotransferase is responsible for the synthesis of the novel cardiovascular risk factor homoarginine

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• 作者：Mariska Davids ; Joseph D.T. Ndika ; Gajja S. Salomons ; Henk J. Blom ; Tom Teerlink
• 关键词：Homoarginine ; Arginine ; glycine amidinotransferase (AGAT) ; Argininosuccinate synthase (ASS) ; Cardiovascular disease
• 刊名：FEBS Letters
• 出版年：2012
• 出版时间：19 October, 2012
• 年：2012
• 卷：586
• 期：20
• 页码：3653-3657
• 全文大小：345 K

文摘

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.