Amino acid signature during sickle cell pain crisis shows significant alterations related to nitric oxide and energy metabolism
Molecular genetics and metabolism
Amino acid; Arginine; Citrulline; Nitric oxide; Pain crisis; Sickle
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.
Zhou, Yun; Yu, Xue; Nicely, Ava; Cunningham, Gary; Challa, Chaitanya; McKinley, Kenneth; Nickel, Robert; Campbell, Andrew; Darbari, Deepika; Summar, Marshall; and Majumdar, Suvankar, "Amino acid signature during sickle cell pain crisis shows significant alterations related to nitric oxide and energy metabolism" (2022). GW Authored Works. Paper 1457.