Glutamate, at the interface between amino acid and carbohydrate metabolism
Glutamate, at the interface between amino acid and carbohydrate metabolism
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DOI：
10.1093/jn/130.4.988s
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发表时间：
2000-04-01
影响因子：
4.2
通讯作者：
Brosnan, JT
中科院分区：
文献类型：
--
作者：
Brosnan, JT
肝脏是尿素生成的主要场所，是氨基酸代谢的主要器官，也是唯一具有完整尿素循环的器官。这些代谢能力是相关的，这些关系最好的例证是检查每日蛋白质负荷的处置。成年人，在典型的西方饮食中，将消耗类似于100 g蛋白质/d;其中大部分由肝脏代谢。虽然教科书表明这些氨基酸在肝脏中被氧化，但在肝脏氧摄取和ATP稳态的范围内不能发生总氧化。相反，大多数氨基酸在肝脏中仅部分氧化，其大部分碳骨架转化为葡萄糖。氮转化为尿素，并在较小程度上转化为谷氨酰胺。尿素循环与尿素异生的整合确保了细胞质中用于尿素异生所需的大量还原能力（NADH）可以由尿素循环的辅助反应提供。谷氨酸是这些代谢事件的中心，原因有三。首先，通过涉及氨基转移酶和谷氨酸脱氢酶的良好描述的脱氨系统，谷氨酸在从氨基酸中去除α-氨基氮中起关键催化作用。第二，氨基酸的“谷氨酸家族”（精氨酸、鸟氨酸、脯氨酸、组氨酸和谷氨酰胺）需要将这些氨基酸转化为谷氨酸以进行代谢处置。第三，谷氨酸作为N-乙酰谷氨酸合成的底物，N-乙酰谷氨酸是氨甲酰磷酸合成酶I（尿素循环中的关键调节酶）的重要变构激活剂。
The liver is the major site of gluconeogenesis, the major organ of amino acid catabolism and the only organ with a complete urea cycle. These metabolic capabilities are related, and these relationships are best exemplified by an examination of the disposal of the daily protein load. Adults, ingesting a typical Western diet, will consume similar to 100 g protein/d; the great bulk of this is metabolized by the liver. Although textbooks suggest that these amino acids are oxidized in the liver, total oxidation cannot occur within the confines of hepatic oxygen uptake and ATP homeostasis. Rather, most amino acids are oxidized only partially in the liver, with the bulk of their carbon skeleton being converted to glucose. The nitrogen is converted to urea and, to a lesser extent, to glutamine. The integration of the urea cycle with gluconeogenesis ensures that the bulk of the reducing power (NADH) required in the cytosol for gluconeogenesis can be provided by ancillary reactions of the urea cycle. Glutamate is at the center of these metabolic events for three reasons. First, through the well-described transdeamination system involving aminotransferases and glutamate dehydrogenase, glutamate plays a key catalytic role in the removal of a-amino nitrogen from amino acids. Second, the "glutamate family" of amino acids (arginine, ornithine, proline, histidine and glutamine) require the conversion of these amino acids to glutamate for their metabolic disposal. Third, glutamate serves as substrate for the synthesis of N-acetylglutamate, an essential allosteric activator of carbamyl phosphate synthetase I, a key regulatory enzyme in the urea cycle.