Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital heinz body hemolytic anemia

The mechanisms of hemoglobin precipitation into Heinz bodies and hemolytic anemia that characterize congenital Heinz body hemolytic anemia (CHBHA) were studied in patients with the unstable hemoglobins, Köln (β-98 valine → methionine) and Hammersmith (β-42 phenylalanine → serine). The cysteines in t...

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Prif Awduron: Jacob, Harry S., Brain, Michael C., Dacie, John V.
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Cyhoeddwyd: 1968
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Mynediad Ar-lein:https://ncbi.nlm.nih.gov/pmc/articles/PMC297438/
https://ncbi.nlm.nih.gov/pubmed/5725279
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spelling pubmed-2974382004-04-12 Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital heinz body hemolytic anemia Jacob, Harry S. Brain, Michael C. Dacie, John V. J Clin Invest Articles The mechanisms of hemoglobin precipitation into Heinz bodies and hemolytic anemia that characterize congenital Heinz body hemolytic anemia (CHBHA) were studied in patients with the unstable hemoglobins, Köln (β-98 valine → methionine) and Hammersmith (β-42 phenylalanine → serine). The cysteines in the 93rd position of the β-chains of CHBHA hemoglobins bound glutathione excessively in mixed disulfide linkage. The resulting diminished “free” GSH within the cell accelerated hexose monophosphate shunt metabolism. The unique precipitability of CHBHA hemoglobins when heated at 50°C could be induced in normal hemoglobin A by artificially blockading its sulfhydryl groups with paramercuribenzoate (PMB). Reflecting the previously reported excessive flux of hemes from hemoglobin Köln, the expected heme/globin ratio in this hemoglobin was reduced by 30%. The further increment in heme loss that occurs with heat (50°C) underlies the unique heat precipitability of CHBHA hemoglobins; it was retarded if detachment of heme was inhibited by cyanide or carbon monoxide. Heinz bodies were attached to red cell membrane thiol groups presumably through mixed disulfide bonds, being released by mercaptoethanol. Binding of hemoglobin Köln-(59)Fe to red cell ghosts, which was markedly enhanced when Heinz bodies were generated at 50°C, was inhibited if membrane thiols were preblockaded by PMB. The depletion of membrane thiols by their reaction with Heinz bodies rendered CHBHA red cells hypersusceptible to membrane sulfhydryl inhibitors, as manifested by inordinate cation leakage, osmotic fragility, and autohemolysis. We conclude that both cellular and membrane thiols bind β-93 sulfhydryls of CHBHA hemoglobins as mixed disulfides. Concomitantly, heme avidity to β-92 lessens, suggesting that degradation of the resulting excessively freed heme may produce the pigmented dipyrroluria of this syndrome. Heinz bodies, reflecting the heightend precipitability of heme-deficient globin, attach to, thereby depleting, membrane sulfhydryl groups. This, as shown previously, could underlie the hemolytic anemia of this syndrome by causing membrane hyperpermeability, premature splenic entrapment, and ultimately osmotic destruction of red blood cells. 1968-12 /pmc/articles/PMC297438/ /pubmed/5725279 Text en
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Articles
spellingShingle Articles
Jacob, Harry S.
Brain, Michael C.
Dacie, John V.
Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital heinz body hemolytic anemia
description The mechanisms of hemoglobin precipitation into Heinz bodies and hemolytic anemia that characterize congenital Heinz body hemolytic anemia (CHBHA) were studied in patients with the unstable hemoglobins, Köln (β-98 valine → methionine) and Hammersmith (β-42 phenylalanine → serine). The cysteines in the 93rd position of the β-chains of CHBHA hemoglobins bound glutathione excessively in mixed disulfide linkage. The resulting diminished “free” GSH within the cell accelerated hexose monophosphate shunt metabolism. The unique precipitability of CHBHA hemoglobins when heated at 50°C could be induced in normal hemoglobin A by artificially blockading its sulfhydryl groups with paramercuribenzoate (PMB). Reflecting the previously reported excessive flux of hemes from hemoglobin Köln, the expected heme/globin ratio in this hemoglobin was reduced by 30%. The further increment in heme loss that occurs with heat (50°C) underlies the unique heat precipitability of CHBHA hemoglobins; it was retarded if detachment of heme was inhibited by cyanide or carbon monoxide. Heinz bodies were attached to red cell membrane thiol groups presumably through mixed disulfide bonds, being released by mercaptoethanol. Binding of hemoglobin Köln-(59)Fe to red cell ghosts, which was markedly enhanced when Heinz bodies were generated at 50°C, was inhibited if membrane thiols were preblockaded by PMB. The depletion of membrane thiols by their reaction with Heinz bodies rendered CHBHA red cells hypersusceptible to membrane sulfhydryl inhibitors, as manifested by inordinate cation leakage, osmotic fragility, and autohemolysis. We conclude that both cellular and membrane thiols bind β-93 sulfhydryls of CHBHA hemoglobins as mixed disulfides. Concomitantly, heme avidity to β-92 lessens, suggesting that degradation of the resulting excessively freed heme may produce the pigmented dipyrroluria of this syndrome. Heinz bodies, reflecting the heightend precipitability of heme-deficient globin, attach to, thereby depleting, membrane sulfhydryl groups. This, as shown previously, could underlie the hemolytic anemia of this syndrome by causing membrane hyperpermeability, premature splenic entrapment, and ultimately osmotic destruction of red blood cells.
author Jacob, Harry S.
Brain, Michael C.
Dacie, John V.
author_facet Jacob, Harry S.
Brain, Michael C.
Dacie, John V.
author_sort Jacob, Harry S.
title Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital heinz body hemolytic anemia
title_short Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital heinz body hemolytic anemia
title_full Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital heinz body hemolytic anemia
title_fullStr Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital heinz body hemolytic anemia
title_full_unstemmed Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital heinz body hemolytic anemia
title_sort altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital heinz body hemolytic anemia
publishDate 1968
url https://ncbi.nlm.nih.gov/pmc/articles/PMC297438/
https://ncbi.nlm.nih.gov/pubmed/5725279
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