Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production
Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production
复制标题
DOI：
10.3945/ajcn.2007.25765
复制
发表时间：
2009-01-01
影响因子：
7.1
通讯作者：
Deutz, Nicolaas E. P.
中科院分区：
文献类型：
--
作者：
Luiking, Yvette C.;Poeze, Martijn;Deutz, Nicolaas E. P.
背景：L-精氨酸是一氧化氮（NO）和蛋白质合成的重要前体。精氨酸在体内（主要是肾脏）通过瓜氨酸的从头生产和蛋白质分解产生。精氨酸的可用性似乎是有限的sepsis.Objective：目的是比较精氨酸和瓜氨酸代谢脓毒症患者和非脓毒症控制患者在重症监护病房（ICU）和健康对照subjects.Design：10例感染性休克患者，7例重症对照患者和16名健康老年人进行了研究。通过使用预充连续（2 h）稳定同位素输注方案测量代谢。NO产量计算为精氨酸转化为瓜氨酸的转化率;从头精氨酸产量计算为瓜氨酸转化为精氨酸的转化率。采集动脉血（健康受试者的动脉化静脉血）用于测定氨基酸富集和浓度。结果：脓毒症患者的全身瓜氨酸生成量（4.5 +/- 2.1 mu mol.kg（-1）.h（-1））显著低于ICU对照患者（10.1 +/- 2.9 mu mol.kg（-1）. h（-1）; P < 0.01）和健康对照受试者（13.7 +/- 4.1 mu mol.kg（-1）.h（-1）; P < 0.001）。因此，脓毒症患者的精氨酸从头生成量（3.3 +/- 3.7 mu mol.kg（-1）.h（-1））低于健康对照组（11.9 +/- 6.6 mu mol.kg（-1）.h（-1）; P < 0.01），脓毒症患者的精氨酸从头生成量往往低于ICU对照组患者（10.9 +/- 9.4 mu mol.kg（-1）.h（-1）; P = 0.05）。脓毒症患者的NO生成低于健康对照组（P < 0.01），而大部分精氨酸在脓毒症中转化为尿素。结论：脓毒症患者的瓜氨酸生成严重低下，与从头精氨酸和NO生成减少有关。这些代谢改变导致瓜氨酸和精氨酸可用性降低，这些发现证明需要进一步研究治疗性营养干预措施，以恢复败血症中的精氨酸代谢。美国临床营养杂志2009; 89：142-52。
Background: L-Arginine is an important precursor of nitric oxide (NO) and protein synthesis. Arginine is produced in the body (mainly kidney) by de novo production from citrulline and by protein breakdown. Arginine availability appears to be limited in sepsis.Objective: The objective was to compare arginine and citrulline metabolism in septic patients and nonseptic control patients in an intensive care unit (ICU) and in healthy control subjects.Design: Ten patients with septic shock, 7 critically ill control patients, and 16 healthy elderly subjects were studied. Metabolism was measured by using a primed continuous (2 h) stable-isotope infusion protocol. NO production was calculated as the conversion rate of arginine to citrulline; de novo arginine production was calculated as the conversion rate of citrulline to arginine. Arterial blood (arterialized venous blood in healthy subjects) was collected for the measurement of amino acid enrichment and concentrations. Data are reported as means +/- SDs.Results: Whole-body citrulline production was significantly lower in septic patients (4.5 +/- 2.1 mu mol.kg(-1).h(-1)) than in ICU control patients (10.1 +/- 2.9 mu mol.kg(-1).h(-1); P < 0.01) and in healthy control subjects (13.7 +/- 4.1 mu mol.kg(-1).h(-1); P < 0.001). Accordingly, de novo arginine production was lower in patients with sepsis (3.3 +/- 3.7 mu mol.kg(-1).h(-1)) than in healthy controls (11.9 +/- 6.6 mu mol.kg(-1).h(-1); P < 0.01) and tended to be lower in septic patients than in ICU control patients (10.9 +/- 9.4 mu mol.kg(-1).h(-1); P = 0.05). NO production was lower in septic patients than in healthy control subjects (P < 0.01), whereas a larger part of arginine was converted to urea in sepsis.Conclusions: Citrulline production is severely low in patients with sepsis and is related to diminished de novo arginine and NO production. These metabolic alterations contribute to reduced citrulline and arginine availability, and these findings warrant further studies of therapeutic nutritional interventions to restore arginine metabolism in sepsis. Am J Clin Nutr 2009; 89: 142-52.