Marini Juan C, Agarwal Umang, Robinson Jason L, Yuan Yang, Didelija Inka C, Stoll Barbara, Burrin Douglas G
Pediatric Critical Care Medicine; and
US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Am J Physiol Endocrinol Metab. 2017 Aug 1;313(2):E233-E242. doi: 10.1152/ajpendo.00055.2017. Epub 2017 Jun 13.
The intestinal-renal axis for endogenous arginine synthesis is an interorgan process in which citrulline produced in the small intestine is utilized by the kidney for arginine synthesis. The function of this axis in neonates has been questioned because during this period the enzymes needed for arginine synthesis argininosuccinate synthase (ASS1) and lyase (ASL) are present in the gut. However, evidence of high plasma citrulline concentrations in neonates suggests otherwise. We quantified in vivo citrulline production in premature (10 days preterm), neonatal (7 days old), and young pigs (35 days old) using citrulline tracers. Neonatal pigs had higher fluxes (69 µmol·kg·h, < 0.001) than premature and young pigs (43 and 45 µmol·kg·h, respectively). Plasma citrulline concentration was also greater in neonatal pigs than in the other age groups. We also determined the site of synthesis and utilization of citrulline in neonatal and young pigs by measuring organ balances across the gut and the kidney. Citrulline was released from the gut and utilized by the kidney in both neonatal and young pigs. The abundance and localization of the enzymes involved in the synthesis and utilization were determined in intestinal and kidney tissue. Despite the presence of ASS1 and ASL in the neonatal small intestine, the lack of colocalization with the enzymes that produce citrulline results in the release of citrulline by the PDV and its utilization by the kidney to produce arginine. In conclusion, the intestinal-renal axis for arginine synthesis is present in the neonatal pig.
内源性精氨酸合成的肠-肾轴是一种器官间过程,其中小肠产生的瓜氨酸被肾脏用于精氨酸合成。该轴在新生儿中的功能一直受到质疑,因为在此期间精氨酸合成所需的酶——精氨琥珀酸合酶(ASS1)和裂解酶(ASL)存在于肠道中。然而,新生儿血浆瓜氨酸浓度高的证据表明情况并非如此。我们使用瓜氨酸示踪剂对早产(早产10天)、新生(7日龄)和幼猪(35日龄)体内的瓜氨酸生成进行了定量。新生猪的通量(69 μmol·kg·h,<0.001)高于早产和幼猪(分别为43和45 μmol·kg·h)。新生猪的血浆瓜氨酸浓度也高于其他年龄组。我们还通过测量肠道和肾脏的器官平衡来确定新生和幼猪体内瓜氨酸的合成和利用部位。在新生和幼猪中,瓜氨酸均从肠道释放并被肾脏利用。我们测定了肠道和肾脏组织中参与合成和利用的酶的丰度和定位。尽管新生小肠中存在ASS1和ASL,但由于缺乏与产生瓜氨酸的酶共定位,导致瓜氨酸由肠外组织释放,并被肾脏用于产生精氨酸。总之,精氨酸合成的肠-肾轴在新生猪中存在。