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 causes polymerization of hemoglobin upon deoxygenation, which results in reduced erythrocyte flexibility, deformation, and numerous theologic effects. However, the wide array of protean complications and the huge variations in the intensity of the manifestations in individual patients are poorly understood. Somatic characteristics and plasma levels of creatinine, L-arginine, hemoglobin, and arginase activity were measured in 19 African-American children and young adults with sickle cell anemia when they were not in overt crises. These parameters were compared with those measured in 16 healthy African-Americans of similar age and gender. Plasma creatinine levels were significantly 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 moles per liter), respectively. Mean L-arginine plasma level was also significantly 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 control subjects. Both plasma hemoglobin and arginase activity values were significantly much higher in the patients than in the controls, with wide differences 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 for more available L-arginine in young persons with this disease may include: 1) increased synthesis of creatine for increased cellular concentrations of creatine for shuttling as reactant for creatine kinase isoenzymatic synthesis of phosphocreatine for many cellular energetics, 2) increased substrate for greater vasoprotection mediated by the arginine nitric-oxide pathway, and 3) correction of a relative deficiency of L-arginine for greater protein synthesis, better immune responses, and better health. (C) 1999 Elsevier Science Inc.