Renal arginine metabolism
Renal arginine metabolism
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DOI：
10.1093/jn/134.10.2791s
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发表时间：
2004-10-01
影响因子：
4.2
通讯作者：
Brosnan, JT
中科院分区：
文献类型：
--
作者：
Brosnan, ME;Brosnan, JT
肾脏在精氨酸代谢中起主要作用有3条途径：精氨酸合成、肌酸合成和精氨酸重吸收。相当数量的精氨酸是由肠道产生的瓜氨酸在肾脏合成的。精氨酸合成的肾酶，精氨酸琥珀酸合成酶和精氨酸琥珀酸裂解酶，存在于近端小管的细胞中。精氨酸合成的速度依赖于瓜氨酸的输送，似乎不受饮食中精氨酸供应的调节。人类的肾脏精氨酸合成产生-2g精氨酸/d，这可以与西方饮食-4-5g/d的摄入量相比较。肌酸和肌酸磷酸的自发、非酶分解为肌酐导致每天1-2g肌酸的排泄，需要从饮食和内源合成中替代等量的肌酸。肌酸生物合成的第一个酶，L-精氨酸：甘氨酸氨基转移酶，发生在肾脏，产生乙酸胍，释放到肾静脉。然而，乙酸胍的肾脏输出量相当低，我们认为肌酸合成的整个途径也可能发生在肝脏。肾精氨酸重吸收回收-3g精氨酸/d。在近端肾小管细胞顶膜，精氨酸与赖氨酸、鸟氨酸和半胱氨酸共用一个转运体。这种异构体转运蛋白的缺陷会导致胱氨酸尿症，其特征也是尿液中精氨酸、赖氨酸和鸟氨酸的丢失。精氨酸通过另一种异构体转运体从基底膜的近端肾小管细胞中转运出来，该转运体也转运赖氨酸和鸟氨酸。这种转运蛋白的缺陷会导致赖氨酸尿蛋白不耐受。
The kidney plays a major role in arginine metabolism in 3 principal ways: arginine synthesis, creatine synthesis, and arginine reabsorption. Appreciable quantities of arginine are synthesized in the kidney from citrulline produced by the intestine. The renal enzymes of arginine synthesis, argininosuccinate synthetase and argininosuccinate lyase, occur in the cells of the proximal tubule. The rate of arginine synthesis depends on citrulline delivery and does not appear to be regulated by dietary arginine availability. Renal arginine synthesis in humans produces -2 g arginine/d, which may be compared to an intake, from a Western diet, of -4 to 5 g/d. Spontaneous, nonenzymatic breakdown of creatine and creatine phosphate to creatinine causes the excretion of 1 to 2 g creatinine/d and requires the replacement of an equivalent amount of creatine from the diet and by endogenous synthesis. The first enzyme of creatine biosynthesis, L-arginine:glycine amidinotransferase, occurs in the kidney and produces guanidinoacetate, which is released into the renal vein. The renal output of guanidinoacetate, however, is rather low, and we propose that the entire pathway of creatine synthesis may also occur in the liver. Renal arginine reabsorption salvages -3 g arginine/d. At the apical membrane of proximal tubular cells, arginine shares a transporter with lysine, ornithine, and cystine. Defects in this heteromeric transporter cause cystinuria, which is also characterized by urinary loss of arginine, lysine, and ornithine. Arginine is transported out of the proximal tubular cells at the basolateral membrane by another heteromeric transporter, which also transports lysine and ornithine. Defects in this transporter cause lysinuric protein intolerance.