Title

Amino acid signature during sickle cell pain crisis shows significant alterations related to nitric oxide and energy metabolism

Authors

Yun Zhou, Divisions of Genetics, Children's National Hospital, George Washington University of Health Sciences, United States of America.
Xue Yu, Department of Data Science, University of Mississippi Medical Center, United States of America.
Ava Nicely, Hematology, Children's National Hospital, George Washington University of Health Sciences, United States of America.
Gary Cunningham, Divisions of Genetics, Children's National Hospital, George Washington University of Health Sciences, United States of America.
Chaitanya Challa, Anesthesia, Children's National Hospital, George Washington University of Health Sciences, United States of America.
Kenneth McKinley, Emergency Department, Children's National Hospital, George Washington University of Health Sciences, United States of America.
Robert Nickel, Hematology, Children's National Hospital, George Washington University of Health Sciences, United States of America.
Andrew Campbell, Hematology, Children's National Hospital, George Washington University of Health Sciences, United States of America.
Deepika Darbari, Hematology, Children's National Hospital, George Washington University of Health Sciences, United States of America.
Marshall Summar, Divisions of Genetics, Children's National Hospital, George Washington University of Health Sciences, United States of America.
Suvankar Majumdar, Hematology, Children's National Hospital, George Washington University of Health Sciences, United States of America. Electronic address: smajumdar@childrensnational.org.

Document Type

Journal Article

Publication Date

8-20-2022

Journal

Molecular genetics and metabolism

Volume

137

Issue

1-2

DOI

10.1016/j.ymgme.2022.08.004

Keywords

Amino acid; Arginine; Citrulline; Nitric oxide; Pain crisis; Sickle

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.

Department

Pediatrics

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