Couchet Morgane, Breuillard Charlotte, Corne Christelle, Rendu John, Morio Béatrice, Schlattner Uwe, Moinard Christophe
Université Grenoble Alpes, Inserm U1055, Laboratory of Fundamental and Applied Bioenergetics, Grenoble, France.
Centre Hospitalier Université Grenoble Alpes, Grenoble, France.
Front Physiol. 2021 Oct 1;12:748249. doi: 10.3389/fphys.2021.748249. eCollection 2021.
Ornithine transcarbamylase (OTC; EC 2.1.3.3) is a ubiquitous enzyme found in almost all organisms, including vertebrates, microorganisms, and plants. Anabolic, mostly trimeric OTCs catalyze the production of L-citrulline from L-ornithine which is a part of the urea cycle. In eukaryotes, such OTC localizes to the mitochondrial matrix, partially bound to the mitochondrial inner membrane and part of channeling multi-enzyme assemblies. In mammals, mainly two organs express OTC: the liver, where it is an integral part of the urea cycle, and the intestine, where it synthesizes citrulline for export and plays a major role in amino acid homeostasis, particularly of L-glutamine and L-arginine. Here, we give an overview on OTC genes and proteins, their tissue distribution, regulation, and physiological function, emphasizing the importance of OTC and urea cycle enzymes for metabolic regulation in human health and disease. Finally, we summarize the current knowledge of OTC deficiency, a rare X-linked human genetic disorder, and its emerging role in various chronic pathologies.
鸟氨酸转氨甲酰酶（OTC；EC 2.1.3.3）是一种普遍存在于几乎所有生物体中的酶，包括脊椎动物、微生物和植物。合成代谢的、大多为三聚体的OTC催化从L-鸟氨酸生成L-瓜氨酸，这是尿素循环的一部分。在真核生物中，这种OTC定位于线粒体基质，部分与线粒体内膜结合，并是通道化多酶复合体的一部分。在哺乳动物中，主要有两个器官表达OTC：肝脏，它是尿素循环的一个组成部分；以及肠道，它合成瓜氨酸以供输出，并在氨基酸稳态中起主要作用，特别是在L-谷氨酰胺和L-精氨酸的稳态中。在此，我们概述OTC基因和蛋白质、它们的组织分布、调控及生理功能，强调OTC和尿素循环酶对人类健康和疾病中代谢调控的重要性。最后，我们总结了目前关于OTC缺乏症（一种罕见的X连锁人类遗传疾病）的知识，以及它在各种慢性病理中的新作用。
