Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida 32610, USA.
Am J Physiol Renal Physiol. 2010 Jan;298(1):F95-102. doi: 10.1152/ajprenal.00487.2009. Epub 2009 Nov 11.
The kidney is a major site of arginine synthesis where citrulline is converted to arginine via argininosuccinate synthase (ASS) and lyase (ASL). The rate-limiting step in arginine synthesis by the normal kidney is the rate of citrulline delivery and uptake to the renal cortex. We tested whether with chronic kidney disease (CKD) renal arginine synthesis may be compromised. Using the 5/6 renal ablation/infarction (A/I) injury model, we measured renal citrulline delivery and uptake as well as arginine release at early, moderate, and severe stages of CKD vs. healthy controls. The renal plasma flow (RPF) and arterial-renal venous difference was measured at baseline and during citrulline infusion. Citrulline delivery was reduced at all stages of disease due to marked reductions in RPF and despite moderately increased plasma citrulline. Early after 5/6 A/I, the kidney demonstrated a compensatory increase in citrulline uptake while at moderate and severe injury baseline citrulline uptake fell. At all stages of CKD, renal arginine release was markedly reduced. Citrulline infusion increased plasma citrulline in all groups, resulting in increased renal delivery vs. baseline. In healthy kidneys and early injury, citrulline uptake increased with the infusion, but only in the normal kidney did arginine production increase in parallel with the increased citrulline uptake. At moderate and severe injury, there was no increase in citrulline uptake or arginine production. The fall in arginine production in 5/6 A/I was due to an early loss of ASS and ASL conversion of citrulline, which combined with a later reduction in citrulline uptake.
肾脏是精氨酸合成的主要部位，其中瓜氨酸通过精氨琥珀酸合成酶（ASS）和裂解酶（ASL）转化为精氨酸。正常肾脏中精氨酸合成的限速步骤是瓜氨酸向肾皮质的输送和摄取速率。我们测试了慢性肾脏病（CKD）是否会损害肾脏精氨酸合成。使用 5/6 肾切除术/梗死（A/I）损伤模型，我们测量了 CKD 早期、中期和晚期与健康对照组相比肾脏瓜氨酸的输送和摄取以及精氨酸的释放。在基础状态和瓜氨酸输注期间测量了肾血浆流量（RPF）和动静脉差异。由于 RPF 明显减少，尽管血浆瓜氨酸适度增加，但疾病的所有阶段瓜氨酸的输送都减少了。在 5/6 A/I 后早期，肾脏表现出瓜氨酸摄取的代偿性增加，而在中度和严重损伤时，基线瓜氨酸摄取下降。在 CKD 的所有阶段，肾脏精氨酸的释放都明显减少。瓜氨酸输注增加了所有组的血浆瓜氨酸，导致与基础值相比，肾脏输送增加。在健康肾脏和早期损伤中，瓜氨酸摄取随着输注而增加，但只有在正常肾脏中，精氨酸的产生才与增加的瓜氨酸摄取平行增加。在中度和重度损伤时，瓜氨酸摄取或精氨酸的产生并没有增加。5/6 A/I 中精氨酸产生的下降是由于 ASS 的早期丧失和 ASL 对瓜氨酸的转化，这与后来瓜氨酸摄取的减少相结合。
