Divisions of Genetics, Children's National Hospital, George Washington University of Health Sciences, United States of America.
Department of Data Science, University of Mississippi Medical Center, United States of America.
Mol Genet Metab. 2022 Sep-Oct;137(1-2):146-152. doi: 10.1016/j.ymgme.2022.08.004. Epub 2022 Aug 20.
Nitric oxide depletion secondary to arginase induced arginine deficiency has been shown to be important in the pathophysiology of vaso-occlusion in sickle cell pain crisis. Our objective of this study was to perform a comprehensive amino acid evaluation during sickle cell pain crisis. In a total of 58 subjects (29 in steady-state sickle cell disease and 29 with sickle cell pain crisis), the amino acids related to nitric oxide pathway was significantly decreased during sickle cell pain crisis compared to steady-state sickle cell disease: arginine (p = 0.001), citrulline (p = 0.012), and ornithine (p = 0.03). In addition, the amino acids related to energy metabolism was significantly decreased during a pain crisis: asparagine (p < 0.001), serine (p = 0.002), histidine (p = 0.017), alanine (p = 0.004), tyrosine (p = 0.012), methionine (p = 0.007), cystine (p = 0.016), isoleucine (p = 0.016) and lysine (p = 0.006). The amino acid related to oxidative stress were significantly higher during a sickle cell pain crisis (glutamic acid (p < 0.001). Furthermore, multivariate analysis with partial least squares-discriminant analysis (PLS-DA) showed that deficiencies of the amino acids arginine, asparagine, citrulline, methionine and alanine were the most important related to sickle cell pain crisis.
由于精氨酸酶诱导的精氨酸缺乏导致的一氧化氮消耗已被证明在镰状细胞疼痛危象的病理生理学中很重要。我们本研究的目的是在镰状细胞疼痛危象期间进行全面的氨基酸评估。在总共 58 名受试者（29 名处于稳定镰状细胞疾病状态，29 名患有镰状细胞疼痛危象）中，与一氧化氮途径相关的氨基酸在镰状细胞疼痛危象期间与稳定镰状细胞疾病相比显着降低：精氨酸（p = 0.001），瓜氨酸（p = 0.012）和鸟氨酸（p = 0.03）。此外，在疼痛危象期间与能量代谢相关的氨基酸显着降低：天冬酰胺（p <0.001），丝氨酸（p = 0.002），组氨酸（p = 0.017），丙氨酸（p = 0.004），酪氨酸（p = 0.012），蛋氨酸（p = 0.007），胱氨酸（p = 0.016），异亮氨酸（p = 0.016）和赖氨酸（p = 0.006）。在镰状细胞疼痛危象期间，与氧化应激相关的氨基酸显着升高（谷氨酸（p <0.001）。此外，偏最小二乘判别分析（PLS-DA）的多元分析显示，氨基酸精氨酸，天冬酰胺，瓜氨酸，蛋氨酸和丙氨酸的缺乏与镰状细胞疼痛危象最相关。
