Engelen Mariëlle P K J, Safar Ahmed M, Bartter Thaddeus, Koeman Fari, Deutz Nicolaas E P
Center for Translational Research in Aging & Longevity, Health and Kinesiology, Texas A&M University, College Station, TX 77843, U.S.A. Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
Department of Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
Clin Sci (Lond). 2016 Jul 1;130(14):1185-95. doi: 10.1042/CS20160233. Epub 2016 Apr 7.
Reduced plasma arginine (ARG) concentrations are found in various types of cancer. ARG and its product nitric oxide (NO) are important mediators in the immune function and the defense against tumour cells. It remains unclear whether the diminished systemic ARG availability in cancer is related to insufficient endogenous ARG synthesis, negatively affecting NO synthesis, and whether a dietary amino acid mixture is able to restore this. In 13 patients with advanced non-small cell lung cancer (NSCLC) and 11 healthy controls, whole body ARG and CIT (citrulline) rates of appearance were measured by stable isotope methodology before and after intake of a mixture of amino acids as present in whey protein. The conversions of CIT to ARG (indicator of de novo ARG synthesis) and ARG to CIT (marker of NO synthesis), and ARG clearance (reflecting ARG disposal capacity) were calculated. Plasma isotopic enrichments and amino acid concentrations were measured by LC-MS/MS. Conversions of CIT to ARG and ARG to CIT (P<0.05), and CIT rate of appearance (P=0.07) were lower in NSCLC. ARG rate of appearance and clearance were comparable suggesting no enhanced systemic ARG production and disposal capacity in NSCLC. After intake of the mixture, ARG rate of appearance and concentration increased (P<0.001), and ARG to CIT conversion was restored in NSCLC. In conclusion, an impaired endogenous ARG synthesis plays a role in the reduced systemic ARG availability and NO synthesis in advanced NSCLC. Nutritional approaches may restore systemic ARG availability and NO synthesis in cancer, but the clinical implication remains unclear.
在各类癌症中均发现血浆精氨酸（ARG）浓度降低。ARG及其产物一氧化氮（NO）是免疫功能及抵御肿瘤细胞的重要介质。目前尚不清楚癌症患者体内全身性ARG可用性降低是否与内源性ARG合成不足有关，进而对NO合成产生负面影响，也不清楚膳食氨基酸混合物能否恢复这一情况。对13例晚期非小细胞肺癌（NSCLC）患者和11名健康对照者，采用稳定同位素方法在摄入乳清蛋白中所含氨基酸混合物前后测定全身ARG和瓜氨酸（CIT）的出现率。计算CIT向ARG的转化（新生ARG合成的指标）、ARG向CIT的转化（NO合成的标志物）以及ARG清除率（反映ARG处置能力）。通过液相色谱-串联质谱法测定血浆同位素富集度和氨基酸浓度。NSCLC患者中CIT向ARG的转化、ARG向CIT的转化（P<0.05）以及CIT出现率（P=0.07）均较低。ARG出现率和清除率相当，表明NSCLC患者全身性ARG生成和处置能力未增强。摄入混合物后，NSCLC患者的ARG出现率和浓度升高（P<0.001），且ARG向CIT的转化恢复正常。总之，内源性ARG合成受损在晚期NSCLC患者全身性ARG可用性降低及NO合成减少中起作用。营养方法可能恢复癌症患者的全身性ARG可用性和NO合成，但临床意义仍不明确。
