Catabolism of hemoglobin by human erythrocyte membranes.

The role of the human erythrocyte membrane in degrading hemoglobin and hemoglobin subunits was investigated by determined the total radioactivity (cpm) of the nascent alpha and beta globin chains attached to the membrane after labeling of intact cells with 14C-leucine. In conditions characterized by balanced globin synthesis (normal and sickle cell anemia), the total radioactivity of membrane-attached alpha globin is always less than membrane-attached beta globin (alpha/beta = 0.60 +/- 0.10) despite the equal synthesis of alpha and beta chains in the hemolysate. In conditions characterized by unbalanced globin synthesis (alpha-thal and beta-thal traits) the cpm of membrane-attached alpha are also less than those of membrane-attached beta. Attachment of globin chains to the membrane is not related to the net ionic charge of individual chains, but the amount of attachment is related to the relative size of the free intracellular alpha chain pool. The alpha/beta ratio of less than 1 is not due to selective attachment of nascent beta chains or selective destruction of nascent alpha chains. The data indicate that part of the discrepancy between membrane and hemolysate alpha/beta radioactivities seen in the conditions studied is due to different rates of entry into the membrane and catabolism of newly labeled globin polypeptide chains by it.