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BLOOD CELLS METABOLISM

BLOOD CELLS METABOLISM. Objectives of the Lecture. 1- Understanding the general structural & functional features of red blood cells (RBCs). 2- Recognizing the main metabolic pathways occurring in RBCs with reference to their relations to functions of RBCs.

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BLOOD CELLS METABOLISM

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  1. BLOOD CELLS METABOLISM

  2. Objectives of the Lecture 1- Understanding the general structural & functional features of red blood cells (RBCs). 2- Recognizing the main metabolic pathways occurring in RBCs with reference to their relations to functions of RBCs. 3- Identifying some of the main & common diseases of RBCs as implication of defects of RBCs metabolism. 4- Understanding the relation of characteristic features of structure of membrane of RBCs. 5-Recognizing the main functions of other blood cells and their metabolism

  3. RBCs Metabolism & Functions Introduction: • RBCs contain nomitochondria, so there is norespiratory chain, nocitric acid cycle, and nooxidation of fatty acids or ketone bodies. • Energy in the form of ATP is obtained ONLYfrom the glycolytic breakdown of glucose with the production of lactate (anaerobic glycolysis). • ATP produced being used for keeping the biconcave shape of RBCs & in the regulation of transport of ions & water in and out of RBCs.

  4. Red Blood Cells(erythrocytes) • Function erythrocyte as a bag forhemoglobin • O2→ transport, reactive oxygen species (ROS) • CO2→ transport, formation of HCO3- • H+→ transport, maintaining pH(35% of blood buffering capacity) • Structure • large surface(for diffusion of gases) • cytoskeletal proteins (for elasticity) • membrane as an osmometer(Na+/K+-ATPase)

  5. RBCs membrane structure • RBCs must be able to squeeze through tight spots in microcirculation (capillaries). For that RBCs must be easily & reversibly deformable. Its membrane must be both fluid & flexible . • About 50% of membrane is protein, 40% is fat & up to 10% is carbohydrate. • RBCs membrane comprises a lipid bilayer (which determine the membrane fluidity), proteins(which is responsible for flexibility) that are either peripheral or integral penetrating the lipid bilayer & carbohydrates that occur only on the external surface. • Defects of proteins may explain some of the abnormalities of shape of RBCs membrane as hereditary spherocytosis & elliptocytosis.

  6. The membrane skeleton is four structural proteins that include  &  spectrin, ankyrin, protein 4.1 & actin • Spectrinis major protein of the cytoskeleton & its two chains ( & ) are aligned in an antiparallel manner .  &  chains are loosely interconnected forming a dimer, one dimer interact with another, forming a head to head tetramer. • Ankyrinbinds spectrin& in turn binds tightly to band 3 securing attachment of spectrin to membrane. • band 3is anion exchange protein permits exchanges of Cl- for HCO3+. • Actin binds to the tail of spectrin& to protein 4.1which in turn binds to integral proteins, glycophorins A, B & C. • GlycophorinsA,B,C are transmembrane glycoproteins

  7. What happens to red blood cells when placed in hypotonic, hypertonic, and isotonic solutions? • acanthocytes • hemolysis • osmolarity(0.9%NaCl)

  8. Red Blood Cells(erythrocytes) • membrane transporters • Na+/K+-ATPase (active transport) • GLUT-1 (insulin independent) • anion exchanger = band 3 protein (Cl-/HCO3-) • membrane antigens • blood groups: ABO system Differ in antigen (glycoprotein) Over the surface of RBCs

  9. Red Blood Cells(erythrocytes) • metabolism • glucose is the main fuel • 90% anaerobic glycolysis(ATP, lactate: Cori cycle; 2,3-BPG) • 10% hexose monophosphate pathway(NADPH) • enzyme defects : * glucose-6-P dehydrogenase * pyruvate kinase→ hemolytic anemia ??? • ATP is generated by anaerobic glycolysis→ ATP is used for ion transport across the cell membrane • glycolysis produces 2,3-BPGand lactate • approx. 5 to 10% of Glc is metabolized by hexose monophosphate pathway → production of NADPH → it is used to maintain glutathione in the reduced state

  10. Red Blood Cells(erythrocytes) 6. Enzymes • carbonate dehydratase (= carbonic anhydrase, CA) CO2 + H2O  HCO3- + H+ • The red cell also contain rhodanaseresponsible for the detoxication of cyanides. • methemoglobin reductase • superoxide dismutase • catalase antioxidative enzyme system • glutathione peroxidase • glutathione reductase

  11. Red Blood Cells(erythrocytes) • Erythropioesis

  12. White Blood Cells(leukocytes) Classification • granulocytes • neutrophils (phagocytosis) • eosinophils (allergy, parasites) • basophils (allergy) • agranulocytes • monocytes→ macrophages • lymphocytes (B, T)→ immunity Reactive oxygen ROS and nitrogen RNS speciesin blood elements ERYTHROCYTES: enzymes for deactivation of ROS formed from high content of oxygen found in the cells PHAGOCYTES:enzymes for production of ROS and RNS to destroy particles in phagosomes

  13. White Blood Cells(leukocytes) Neutrophils (microphages) • high content of lysosomes (hydrolytic enzymes) • few mitochondria • glucosedependent: NADPH production • NADPH is used for production of reactive oxygen species → they kill bacteria

  14. Basofils contain heparin and histamine

  15. B-lymphocytes produce antibodies (= immunoglobulins, -globulins)

  16. Platelets(thrombocytes) participate in hemostasis

  17. Platelets(thrombocytes)

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