Presentation on theme: "Eric Niederhoffer SIU-SOM What affects the normal functions of an erythrocyte? A 4-year-old African boy is brought in by his adoptive parents who say that."— Presentation transcript:
Eric Niederhoffer SIU-SOM What affects the normal functions of an erythrocyte? 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
RBC Metabolic Pathways 2,3-BPG BPG mutase 2,3-BPG phosphatase PPP NADPH 6PG 3-7 C metabolites (R5P, F6P, G3P) G6PDH lactonase 6PGDH CO 2 NADP + + H + GSH GSSG GR GP H2O2H2O2 H2OH2O Glc Pyr G6P 1,3-BPG 3PG HK PGI PK F6P G3P PFK aldolase F16BP DHAP 2PG PEP PGK PGM enolase G3PDH Glycolysis Lactate No O 2 LDH
Hemoglobin Genes and Gene Products http://www.mun.ca/biology/desmid/brian/BIOL3530/DB_Ch09/fig9_24.jpg
Hemoglobin Gene Product Production Mehta, A. B., and A. V. Hoffbrand. 2000. Haematology at a glance, Blackwell Science, Malden, Mass. HbF: 2α and 2γ HbA1: 2α and 2β HbA2: 2α and 2δ HbE: 2ζ and 2ε Yolk sacLiverSpleenBone marrow
Sickle Cell Disease http://www.emedicine.com/ped/TOPIC2096.HTM Rare combinations of HbS with HbD Los Angeles, HbO Arab, G-Philadelphia, among others (>6 major genotypes) at least 1 sickle gene, hemoglobin S (HbS) ≥ 50% Hb present. homozygotic HbSS (sickle cell anemia) - HbS = 100% Hb present HbSbeta-0 thalassemia - Severe double heterozygote for HbS and beta-0 thalassemia; almost indistinguishable from sickle cell anemia phenotypically (MCV low) HbSC disease - Double heterozygote for HbS and HbC, with intermediate clinical severity HbS/hereditary persistence of fetal hemoglobin (S/HPHP) - Mild form or symptom free HbS/HbE syndrome - Rare and generally mild clinical course
Hemoglobin Electrophoresis http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.html Homozygous HbS Normal neonate Normal adult HbSC Heterozygous HbS Relative protein charge
Molecular Changes of HbS http://www.sicklecellinfo.net/fiberformation.htm. Daniel J. Harrington, D. J., K. Adachi, and W. E. Royer, Jr. 1997. J. Mol. Biol. 272(3):398-407 Heme Val
Molecular and Cellular Changes of HbS http://www.emedicine.com/ped/TOPIC2096.HTM Decreased P O 2 Permanent damage to RBC Cellendothelium interactions
Effects of Therapy with Hydroxyurea http://www.emedicine.com/ped/TOPIC2096.HTM ★★★
Review Questions What proteins compose the membrane of erythrocytes? What metabolic pathways are used in erythrocytes? What is hemoglobin; what changes with sickle cell disease? What clinical observations would you make concerning patients with SCD? What are the thalassemias?
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