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)