{Reference Type}: Journal Article {Title}: Amino acid signature during sickle cell pain crisis shows significant alterations related to nitric oxide and energy metabolism. {Author}: Zhou Y;Yu X;Nicely A;Cunningham G;Challa C;McKinley K;Nickel R;Campbell A;Darbari D;Summar M;Majumdar S;Zhou Y;Yu X;Nicely A;Cunningham G;Challa C;McKinley K;Nickel R;Campbell A;Darbari D;Summar M;Majumdar S; {Journal}: Mol Genet Metab {Volume}: 137 {Issue}: 1 {Year}: Aug 2022 20 {Factor}: 4.204 {DOI}: 10.1016/j.ymgme.2022.08.004 {Abstract}: 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.