Effects of cyanate and 2,3-diphosphoglycerate on sickling. Relationship to oxygenation.
Cyanate and 2,3-diphosphoglycerate (2,3-DPG) both influence the oxygen affinity of hemoglobin. The studies presented here concern the effects of these compounds on the sickling phenomenon. The inhibitory effect of cyanate on sickling is largely due to the fact that it increases the percentage of oxyhemoglobin S at a given oxygen tension. In addition, cyanate inhibits sickling by a mechanism that is independent of oxygenation. In this paper, we have demonstrated that the viscosity of carbamylated sickle blood was lower than that of non-carbamylated controls at the same oxygen saturation. Furthermore, carbamylation resulted in an increase in the minimum concentration of deoxy-sickle hemoglobin required for gelation. Like cyanate, 2,3-DPG affected sickling of intact erythrocytes by two mechanisms. Since 2,3-DPG decreases the percentage of oxyhemoglobin S at a given oxygen tension, sickling is enhanced. In addition, 2,3-DPG had a direct effect. When the intracellular 2,3-DPG concentration was increased in vitro, a greater percentage of cells were sickled at a given oxygen saturation. Conversely, sickling was inhibited in cells in which 2,3-DPG was artificially lowered. These data indicate that the enhancement of sickling by 2,3-DPG is in part independent of its influence on oxygen affinity.
D000755:Anemia, Sickle Cell / Q000097:blood*; D003485:Cyanates / Q000494:pharmacology*; D004163:Diphosphoglyceric Acids / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects*; D005988:Glyceric Acids / Q000494:pharmacology*; D006400:Hematocrit; D006451:Hemoglobin, Sickle; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007288:Inosine / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010108:Oxyhemoglobins / Q000378:metabolism; D010710:Phosphates / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology; D013447:Sulfites / Q000494:pharmacology; D014783:Viscosity
D003485:Cyanates; D004163:Diphosphoglyceric Acids; D005988:Glyceric Acids; D006451:Hemoglobin, Sickle; D006454:Hemoglobins; D009943:Organophosphorus Compounds; D010108:Oxyhemoglobins; D010710:Phosphates; D011773:Pyruvates; D013447:Sulfites; D007288:Inosine; D010100:Oxygen