Abnormal red cell membrane proteolytic activity in severe heterozygous beta-thalassemia.
A 63-year-old man of italian origin with severe heterozygous beta-thalassemia whose clinical condition deteriorated after splenectomy is described. The alpha/beta synthesis ration in the peripheral blood was 3.02 +/- 0.56 and in the bone marrow 1.43. The free alpha-chain pool comprised 73% of the total radioactive alpha-globin in the peripheral blood and 68% in the bone marrow. RBC membranes isolated from erythrocytes incubated in the presence of 14C-leucine were practically devoid of nascent beta-chains with an alpha/beta ratio of 5.12 +/- 1.47, significantly higher than that present in the corresponding hemolysate. RBC membranes from this patient, compared to control membrane preparations, showed increased proteolytic activity directed against tetrameric hemoglobin and beta-hemoglobin chains, with concomitant decreased catabolism of alpha-hemoglobin chains. RBC membranes from individuals with mild beta-thalassemia trait and from transfused patients with homozygous beta-thalassemia degraded alpha-hemoglobin chains more efficiently than those from the patient described. The data suggest that decreased degradation of the alpha-chain by RBC membranes from this patient might lead to progressive accumulation of this polypeptide and expansion of the free alpha-chain pool, which, in turn, may be responsible for the severity of the clinical picture.
D001853:Bone Marrow / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005914:Globins / Q000096:biosynthesis; D006441:Hemoglobin A / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D066298:In Vitro Techniques; D007930:Leucine / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D013789:Thalassemia / Q000151:congenital / Q000378:metabolism* / Q000601:surgery
D011480:Protease Inhibitors; D005914:Globins; D006441:Hemoglobin A; D010447:Peptide Hydrolases; D007930:Leucine