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Erythrocytes
Anucleate and no mitochondria for metabolizing

fatty or amino acids

ERYTHROCYTE METABOLISM

Derives energy from breakdown of glucose

Processes which Requires Energy

Maintenance of the following:

Glycolysis

Intracellular cationic gradient Membrane phospholipid Skeletal protein plasticity Functional ferrous hemoglobin

Glucose enters thru facilitated transport

Anaerobic metabolism Aerobic metabolism

Protection from oxidative degeneration Initiation and maintenance of glycolysis Glutathione synthesis Neucleotide salvage mechanisms

Anaerobic Metabolism
Comprises 90-95% of glucose consumption All enzymes are fond in the cytosol

Ebden-Meyerhof Pathway

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Reaction 1
Glucose phosphorylated by Hexokinase to Glucose 6- Phosphate
Uses ATP as phosphate donor Essentially irreversible Hexokinase

Lowest activity among glycolytic enzymes Inhibited by G6P Increased activity when H+ ion concentration is high

Reaction 2
Glucose 6 phosphate undergoes aldoseketose isomerization by phosphoisomerase
Product: Fructose 6 Phosphate G6P: important and serves as the junction of other

metabolic pathways
Glycolysis Gluconeogenesis Pentose phosphate pathway Glycogenesis Glycogenolysis

Reaction 3
Phosphorylization of F6P by phosphofructokinase to Fructose 1,6 bisphosphate
Uses ATP as phosphate source Irreversible

Phosphofructokinase is regulated by ADP, H+ ion,

and inorganic phosphates

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Reaction 4

Cleavage of F1,6P aldolase

Products: Glyceraldehyde 3 phosphate and

dihydroxyacetone phosphate
Interconverted by phosphotriose isomerase

Reaction 5
Glyceraldehyde 3 phosphate is oxidized by Glyceraldehyde 3 phosphatedehydrogenase
Product: 1,3 bisphoglycerate Enzyme is NAD dependent

Available as a cofactor for reduction of methemoglobin

Reaction 6
Substrate level phosphorylation of ADP into ATP
1,3 biphosphoglycerate is converted to 3

phosphoglycerate
Catalyzed by phosphoglycerate kinase 1,3 bisphosphoglycerate may also be shunted to another pathway

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Reaction 7

Isomerization of 3 phosphoglycerate by

phosphoglycerate mutase
Product: 2 phosphoglycerate

Reaction 8
Dehydration of 2 phosphoglycerate by enolase
Product: phosphoenolpyruvate Enolase inhibited by fluoride

Reason why you can use fluoride as additive for glucose determination

Reaction 9
Phosphate transfer from phosphoenolpyruvate to ADP by pyruvate kinase
Product: ATP and enolpyruvate

Enolpyruvate spontaneously isomerizes to pyruvate Pyruvate kinase reaction is irreversible

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Reaction 10
Redox state of the body dictates which pathway is followed
Anaerobic:

Pyruvate is reduced by NADH to lactate Enzyme: LDH

Allows glycolysis to proceed without oxygen by producing NAD for another cvycle of use in glyceradlehyde 3 phosphate dehydorgenase

Rapaport Luebering Pathway

Aerobic

Pyruvate is taken up by mitochondria and metabolized by the citric acid cycle RBC: No mitochondria hence, inapplicable.

Reaction catalized by phosphoglycerate may be bypassed

Rapaprot Luebering Pathway Dissipates the free energy from 1,3 BPG as heat

Rapaport Luebering Pathway

Involves no net yield of ATP Provide 2,3 bisphophoglycerate phosphatase Most concentrated organophosphate in RBC

Binds to hemoglobin to decrease its affinity to oxygen

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Aerobic Glycolysis
Diverts glucose metabolism into Hexome monophosphate shunt
Diverts 10% of G6P Maintains reduced glutathione and reduced NADP

Ribulose 5 phosphate
Used for nucleotide metabolism

May re-enter anaerobic glycolysis pathways

Nucleotide Metabolism
NADPH
Reduces oxidized glutathione via glutathione

Nucleotides cannot be synthesized and must be maintained:

ATP 88% ADP 10% AMP 2%

reductase
Can convert hydrogen peroxide to water in

presence of glutathione peroxidase

Accumulation oh H2O2 decreases RBC lifespan

Maintained by adenylate cyclase and glycolysis May also be salvaged by adenosine phosphoribosyl transferase which converts adenine to AMP

Erythrocyte Membrane
Main functions:
Maintain cell shape and deformibility Maintain osmotic balance Act as supporting skeletal system for surface

Composition
Lipid bilayer: 40% lipid, 58% protein, 8 carbohydrate

antigens and receptors

Aid in ion and gas transport

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Glycophorins
Transmembrane protein extending across the lipid

Band 3
Ion exchange channel Forms key site of attachment of RBC membrane

layer once A:
Trasmembrane antigen that is heavily glycosylated and extrudes to the surface of the RBC Contains 90% of sialic acid and forms basis of MN blood group system Binding sites for influenza and plasmodium

to cytoskeleton
Associated with ABO antigens Senescence antigen

Membrane Protein Skeleton

Interlocking network of proteins for defomability and elasticity Supports the lipid layer and supplies the peripheral proteins
Spectrin
Major protein of the cytoskeleton (5070%) Composed of Alpha and beta chains antiparallel

manner and loosely intertwined into a dimer

Each dimer interacts with another Confers flexibility Contains 4 binding sites Self association Ankyrin Actin Protein 4.1

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Ankyrin
Pyramid shaped protein Binds tightly to band 3 to secure attachemnt of

spectrin to membrane Sensitive to rproteolysis

Actin
Short double helical filaments of F actin
Binds with the tail end of Spectrin Binds with protein 4.1

End
Protein 4.1
Globular protein bound tight to the tail end of

spectrin near the actin binding site.

Binds glycophorin A and C

Attaches the glycophorins to the membrane

Interacts with phospholipids

Attaches lipid bilayer to cytockeleton