The effects of oxygen affinity and gelation of hemoglobin S crosslinked by reaction with methyl acetimidate. 1981

T L Chao, and M R Berenfeld, and T Gelbart, and T G Gabuzda

The contribution of the high molecular weight hemoglobin (HMW Hb) to the antisickling effect produced by treatment of sickle cell erythrocytes with methyl acetimidate (MAI) was investigated. Erythrocytes obtained from sickle cell anemia and normal individuals were incubated with varying concentrations of MAI. The presence of intermolecularly crosslinked HMW Hb was detected by gel filtration of dialyzed hemolysates obtained from the incubated cells. HMW Hb has an increased oxygen affinity and a decreased Hill constant. Intermolecular crosslinking per se was shown to have no additional effect on Hb oxygen affinity other than that due to Hb amino group modification. Modified deoxy Hb S of normal molecular weight has a higher minimum gel concentration (MGC) than control deoxy Hb S. Deoxy HMW Hb did not gel at intracellular Hb concentrations. Therefore, the intracellular concentration of deoxy Hb S that gels necessarily decreases as the HMW Hb concentration increases. This "excluded volume effect" of the non-gelling Hb would be expected to increase the MGC of completely deoxygenated hemolysate obtained from the treated cells. The HMW Hb contributes to the inhibition of sickling resulting from treatment of sickle erythrocyte with MAI by increasing both MGC and oxygen affinity of the modified Hb.

UI MeSH Term Description Entries
D007096 Imidoesters Esters of the hypothetical imidic acids. They react with amines or amino acids to form amidines and are therefore used to modify protein structures and as cross-linking agents. Imidates
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D010100 Oxygen An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration. Dioxygen,Oxygen-16,Oxygen 16
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D002850 Chromatography, Gel Chromatography on non-ionic gels without regard to the mechanism of solute discrimination. Chromatography, Exclusion,Chromatography, Gel Permeation,Chromatography, Molecular Sieve,Gel Filtration,Gel Filtration Chromatography,Chromatography, Size Exclusion,Exclusion Chromatography,Gel Chromatography,Gel Permeation Chromatography,Molecular Sieve Chromatography,Chromatography, Gel Filtration,Exclusion Chromatography, Size,Filtration Chromatography, Gel,Filtration, Gel,Sieve Chromatography, Molecular,Size Exclusion Chromatography
D003432 Cross-Linking Reagents Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other. Bifunctional Reagent,Bifunctional Reagents,Cross Linking Reagent,Crosslinking Reagent,Cross Linking Reagents,Crosslinking Reagents,Linking Reagent, Cross,Linking Reagents, Cross,Reagent, Bifunctional,Reagent, Cross Linking,Reagent, Crosslinking,Reagents, Bifunctional,Reagents, Cross Linking,Reagents, Cross-Linking,Reagents, Crosslinking
D004912 Erythrocytes Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN. Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006451 Hemoglobin, Sickle An abnormal hemoglobin resulting from the substitution of valine for glutamic acid at position 6 of the beta chain of the globin moiety. The heterozygous state results in sickle cell trait, the homozygous in sickle cell anemia. Hemoglobin S,Deoxygenated Sickle Hemoglobin,Deoxyhemoglobin S,Hemoglobin SS,Hemoglobin, Deoxygenated Sickle,SS, Hemoglobin,Sickle Hemoglobin,Sickle Hemoglobin, Deoxygenated
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000596 Amino Acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Amino Acid,Acid, Amino,Acids, Amino

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