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BLOOD CELLS METABOLISM
Objectives of the LectureObjectives of the Lecture
1- Understanding the general structural & functional features of red blood 1- Understanding the general structural & functional features of red blood cells (RBCs).cells (RBCs).
2- Recognizing the main metabolic pathways occurring in RBCs with 2- Recognizing the main metabolic pathways occurring in RBCs with reference to their relations to functions of RBCs.reference to their relations to functions of RBCs.
3- Identifying some of the main & common diseases of RBCs as implication 3- Identifying some of the main & common diseases of RBCs as implication of defects of RBCs metabolism.of defects of RBCs metabolism.
4- Understanding the relation of characteristic features of structure of 4- Understanding the relation of characteristic features of structure of membrane of RBCs.membrane of RBCs.
5-Recognizing the main functions of other blood cells and their 5-Recognizing the main functions of other blood cells and their metabolismmetabolism
IntroductionIntroduction:• RBCs contain nono mitochondria, so there is nono
respiratory chain, nono citric acid cycle, and nono oxidation of fatty acids or ketone bodies.
• Energy in the form of ATP is obtained ONLYONLY from the glycolytic breakdown of glucose with the production of lactate (anaerobic glycolysis).
• ATPATP produced being used for keeping the biconcave
shape of RBCs & in the regulation of transport of ions & water in and out of RBCs.
RBCs Metabolism & FunctionsRBCs Metabolism & Functions
Red Blood Cells (erythrocytes)
1. Functionerythrocyte as a bag for hemoglobin
O2 → transport, reactive oxygen species (ROS)
CO2 → transport, formation of HCO3-
H+ → transport, maintaining pH(35% of blood buffering capacity)
2. Structure large surface
(for diffusion of gases)
cytoskeletal proteins (for elasticity)
membrane as an osmometer(Na+/K+-ATPase)
• 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 fluidfluid & flexibleflexible .
• About 50% of membrane is protein, 40% is fat & up to 10% is carbohydrate.
• RBCs membrane comprises a lipid bilayer lipid bilayer (which determine the membrane fluidityfluidity), proteinsproteins (which is responsible for flexibilityflexibility) that are either peripheral or integral penetrating the lipid bilayer & carbohydratescarbohydrates that occur only on the external surface.
• Defects of proteins may explain some of the abnormalities of Defects of proteins may explain some of the abnormalities of shape of RBCs membrane as shape of RBCs membrane as hereditary spherocytosishereditary spherocytosis & & elliptocytosiselliptocytosis..
RBCs membrane structureRBCs membrane structure
The membrane skeleton is four structural proteins that include & spectrinspectrin, ankyrinankyrin, protein 4.1 protein 4.1 & actinactin
•Spectrin Spectrin is 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.•Ankyrin Ankyrin binds spectrin spectrin & in turn binds tightly to band 3band 3 securing attachment of spectrin to membrane.•band 3band 3 is anion exchange protein permits exchanges of Cl- for HCO3
+.•Actin Actin binds to the tail of spectrin spectrin & to protein 4.1protein 4.1 which in turn binds to integral proteins, glycophorins A, B & C.•GlycophorinsGlycophorins A,B,C are transmembrane glycoproteinsglycoproteins
• hemolysis
What happens to red blood cells when placed in hypotonic, hypertonic, and isotonic
solutions?
• osmolarity(0.9%NaCl)
• acanthocytes
Red Blood Cells (erythrocytes)
3. membrane transporters Na+/K+-ATPase (active transport)
GLUT-1 (insulin independent)
anion exchanger = band 3 protein (Cl-/HCO3-)
4. membrane antigens blood groups: ABO system
Differ in antigen (glycoprotein)
Over the surface of RBCs
Red Blood Cells (erythrocytes)
5. 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-BPG and 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
Red Blood Cells (erythrocytes)6. Enzymes
carbonate dehydratase (= carbonic anhydrase, CA) COCO22 + H + H22O O HCO HCO33
-- + H + H++
The red cell also contain rhodanase responsible for the detoxication of cyanides.
methemoglobin reductase
superoxide dismutase
catalase antioxidative enzyme system
glutathione peroxidase
glutathione reductase
Red Blood Cells (erythrocytes)6. Erythropioesis
White Blood Cells (leukocytes)Classification• granulocytes
neutrophils (phagocytosis)eosinophils (allergy, parasites)basophils (allergy)
• agranulocytesmonocytes → macrophages lymphocytes (B, T) → immunity
Reactive oxygen ROS and nitrogen RNS species in 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
White Blood Cells (leukocytes)
Neutrophils (microphages)
high content of lysosomes (hydrolytic enzymes)
few mitochondria
glucose dependent: NADPH production
NADPH is used for production of reactive oxygen species → they kill bacteria
Basofils
contain heparin and histamine
B-lymphocytes
produce antibodies (= immunoglobulins, -globulins)
Platelets(thrombocytes)
participate in hemostasis
Platelets(thrombocytes)
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