Evidence that L-arginine is a key amino acid in sickle cell anemia - A preliminary report

A molecular hemoglobin defect as a point mutation in sickle cell anemia cau ses polymerization of hemoglobin upon deoxygenation, which results in reduc ed erythrocyte flexibility, deformation, and numerous theologic effects. Ho wever, the wide array of protean complications and the huge variations in t he intensity of the manifestations in individual patients are poorly unders tood. Somatic characteristics and plasma levels of creatinine, L-arginine, hemoglobin, and arginase activity were measured in 19 African-American chil dren and young adults with sickle cell anemia when they were not in overt c rises. These parameters were compared with those measured in 16 healthy Afr ican-Americans of similar age and gender. Plasma creatinine levels were sig nificantly lower in subjects with sickle cell anemia. Mean values were 0.56 +/- 0.19 mg/dl (49.5 +/- 16.8 mu moles per liter) in the males and 0.42 +/ - 0.10 mg/dl (37.1 +/- 8.8 mu moles per liter) in the females. In male and female controls, plasma creatinine levels averaged 0.97 +/- 0.26 mg/dl(85.7 +/- 23.0 mu moles per liter) and 0.79 +/- 0.19 mg/dl (69.8 +/- 16.8 mu mol es per liter), respectively. Mean L-arginine plasma level was also signific antly lower in the patients. Values measured 57.8 +/- 12.0 and 79.0 +/- 13. 6 mu M (mean +/- SD) in the patients and controls, respectively. Levels of L-arginine ranged lower also, from 34.9 to 75.6 mu M, in the 19 sickle-cell -anemia patients. L-arginine ranged from 57.0 to 103.9 mu M in the 16 contr ol subjects. Both plasma hemoglobin and arginase activity values were signi ficantly much higher in the patients than in the controls, with wide differ ences in individual patients. Height and weight were significantly less in the subjects with sickle cell anemia. Therefore, L-arginine appears to be a key conditionally essential amino acid in sickle cell anemia. Key needs fo r more available L-arginine in young persons with this disease may include: 1) increased synthesis of creatine for increased cellular concentrations o f creatine for shuttling as reactant for creatine kinase isoenzymatic synth esis of phosphocreatine for many cellular energetics, 2) increased substrat e for greater vasoprotection mediated by the arginine nitric-oxide pathway, and 3) correction of a relative deficiency of L-arginine for greater prote in synthesis, better immune responses, and better health. (C) 1999 Elsevier Science Inc.