A 4-year-old African boy is brought in by his adoptive parents who say that he has pain in his limbs and does not want to walk A 40-year-old man complains of progressive exertional shortness of breath How are CO2, NO, and O2 processed and transported? How is heme synthesized? Eric Niederhoffer SIU-SOM Small Molecule Processing and Transport • CO2 processing and transport carbonic anhydrase, anion exchanger, carbamate formation, Bohr effect • NO processing and transport glutathione • O2 processing and transport hemoglobin/myoglobin structure, allostery, cooperativity • Heme synthesis pathway, disorders CO2 Processing and Transport CO2 from tissues CO2 H2O CA HbNH2 H2CO3 + Hb(O2)4 + H+ + HbNH-CO2ClAE1 HCO 3 ClHCO3- + H+Hb + O2 plasma O2 to tissues Percent Distribution of CO2 Species Arterial Venous Carbamino 5 30 HCO3CO2 dissolved CO2 to air CO2 H2O CA HbNH2 H2CO3 + Hb(O2)4 + H+ + HbNH-CO2AE1 ClHCO3plasma ClHCO3- + H+Hb + O2 O2 from air 87 8 60 10 NO Processing and Transport http://www.comprehensivephysiology.com/WileyCDA/CompPhysArticle/refId-c090009.html Hemoglobin Structure Changes http://www.mfi.ku.dk/PPaulev/chapter8/images/8-3.jpg Factors Affecting Binding of O2 Depends on pH ([H+]), CO2, BPG, Temp Factors Affecting Binding of O2 Adaptation Figures from http://www.wiley.com/college/voet/047119350X/image_gallery /ch10/index.html Heme Synthesis mit SCoA + Gly 5-Aminolevulinic acid synthase Porphobilinogen synthase PBG 5ALA PBG deaminase Heme Hydroxymethylbilane Ferrochelatase Uroporphyrinogen III synthase UPGIII PPIX UPGIII decarboxylase Coproporphyrinogen oxidase CPGIII PPGIX Protoporphyrinogen oxidase Review Questions • How are CO2 and NO processed and transported? • How are myoglobin and hemoglobin similar and different? • What portion of hemoglobin is involved in small molecule transport? • What allosteric effectors bind hemoglobin? • How do allosteric effectors produce left and right shifts of the hemoglobin-O2 binding curves? • How is heme synthesized? • How is heme synthesis regulated?