Nitrogen metabolism in sickle cell anemia: free amino acids in plasma and urine

Twenty-four hour urinary levels and fasting plasma concentrations of free amino acids (AA) were evaluated in adult sickle cell anemia (HbSS) and age-matched HbAA subjects with comparable daily energy (E) and protein (N) intake. HbSS elicited significant reduction in the sum of plasma indispensable (EAA) with no change in the dispensable (NAA) amino acids, resulting in a prominent (P less than 0.01) reduction in the EAA/NAA ratio from 71% to 55%. Arg (-38%), Leu (-32%), Val (-28%) and His (-32%) were among the AA most severely affected. Despite a twofold increase in 24-hour urine volume in HbSS compared with HbAA subjects, total urinary losses of EAA and NAA were markedly reduced in the former group, with Arg (-53%) and Gly (-56%) levels most prominently affected. Compared with HbAA controls, HbSS subjects showed a three-fourfold increase in 24-hour urinary orotate excretion that had no relationship to amount of N intake. The results indicated that adult subjects with HbSS, who consumed adequate N and E as per the RDA for healthy individuals, behaved like normal HbAA controls on a low protein diet. There was evidence that the HbSS subject might be in a precarious state with respect to sufficiency of several amino acids, particularly L-Arg, which is now classified as conditionally indispensable for the human.