RBC membrane RBC metabolism Erythrocyte Membrane and Membrane Structure & Function RBC membrane Topic 5 RBC metabolism Lecturer: Marilyn Garzon, MSMT, MLT Anucleated No organelles Biconcave Volume: 90 fL (ave) Lifespan: 100 days (ave) Nucleus: extruded (Metarubricyte last nucleated stage) Cytoplasmic ribosomes & mitochondria: disappear 24-48 hrs after BM release Cytoplasm: Hemoglobin Biconcave: deformability Limited lifespan: energy metabolism RBC metabolism • • • • • RBC membrane structure Erythrocytes Membrane Composition & Structure allow the membrane to perform 3 basic functions: Composition: Lipids (40%) Phospholipids (lipid bilayer) Unesterified cholesterol – regulate membrane fluidity and permeability Stained peripheral blood smear showing normal red cells & a lymphocyte RBC metabolism 1. Separate intracellular and extracellular fluid environments 2. Selective passage of nutrients and ions 3. Allow cell to deform when required Proteins (52%) Cytoskeletal/Peripheral proteins RBC metabolism - principal: α- and β- Spectrin - lateral/horizontal stability - deformability - other: ankyrin protein 4.1 actin adducin dermatin tropomyosin tropomodulin Transmembrane/Integral proteins - vertical stability/anchorage - structural integrity - serve as transport & adhesion sites and signaling receptors - principal: Band 3 - support blood group antigens (ABH, MNSs, Rh systems) Membrane enzyme systems: 1. Na+,K+ ATPase - K+ : major intracellular cation - Na+: major extracellular cation RBC metabolic processes requiring energy for: • Maintenance of: Intracellular cationic gradient Membrane phospholipid distribution *Aquaporin I – transmembrane protein that forms pores/channels Functional hemoglobin (Fe2+) Hemoglobin Viscosity *RBCs become less deformable and more susceptible to lysis: - Loss of cellular water - Hb is: precipitated (Heinz bodies) polymerized (Hb S) crystallized (Hb C) Skeletal protein deformability • Protection of cell proteins from oxidative denaturation • Glycolysis initiation and maintenance • Glutathione synthesis • Nucleotide salvage reactions RBC metabolism 2. Ca+2-ATPase - Calcium pump - controlled by Calmodulin Membrane enzyme systems: 1. Na+,K+ ATPase - K+ : major intracellular cation - Na+: major extracellular cation RBC metabolic processes requiring energy for: • Maintenance of: Intracellular cationic gradient Membrane phospholipid distribution *Aquaporin I – transmembrane protein that forms pores/channels Functional hemoglobin (Fe2+) Hemoglobin Viscosity *RBCs become less deformable and more susceptible to lysis: - Loss of cellular water - Hb is: precipitated (Heinz bodies) polymerized (Hb S) crystallized (Hb C) Skeletal protein deformability • Protection of cell proteins from oxidative denaturation • Glycolysis initiation and maintenance • Glutathione synthesis • Nucleotide salvage reactions RBC metabolism 2. Ca+2-ATPase - Calcium pump - controlled by Calmodulin Embden-Meyerhof Pathway (EMP) Anaerobic glycolysis Glucose catabolized to Pyruvate (uses 2 ATP to generate 4 ATP = net gain of 2 ATP) Glycolysis Diversion Pathways (Shunts) 1. Hexose Monophosphate Pathway (Pentose Phosphate Shunt) Aerobic process Detoxifies peroxide (H2O2) Extends lifespan of RBCs Diverts Glucose-6-phosphate to ribulose-5-phosphate by glucose-6phosphate-dehydrogenase (G-6-PD) Generation of reduced glutathione - Protects RBC from oxidative damage 2. Methemoglobin Reductase Pathway Peroxide oxidizes Fe2+ to Fe3+ producing Methemoglobin or Hemiglobin Methemoglobin reductase or cytochrome b5 reductase - act as electron carrier - 65% of methemoglobin reducing capacity of RBCs 3. Rapoport-Luebering Pathway Generation of 2,3-diphosphoglycerate (2,3-DPG; or 2,3-biphosphoglycerate/ 2,3-BPG) - regulates O2 delivery to tissues Summary: References: 1. Membrane composition and function Keohane,E et al (2016). Rodak’s Hematology a. Lipids b. Proteins - cytoskeletal proteins - integral proteins - membrane enzyme systems Hemoglobin viscosity 2. Red cell membrane metabolism a. Embden-Meyerhof Pathway - Hexose-Monophosphate Pathway - Methemoglobin Reductase Pathway - Rapoport-Luebering Shunt Clinical Principles and Applications 5th edition. Lotspeich-Steininger, C. et al (1992). Clinical Hematology Principles, Procedures, Correlations.
