RBC Metabolism and Membrane Flashcards by Penny Nichols

What are the three glycolosis diversion pathways RBCs use for energy?

Hexose monophosphate
Methhemoglobin reductase
Rapaport-Luebering

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What are the three areas of RBC metabolism that are crucial for normal (RBC) survival and function?

RBC metabolic pathways
RBC membrane
Hemoglobin structure and function

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What is the reason behind hemolytic anemias?

Defects in one of the three areas of RBC metabolism

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What is RBC senescense?

What happens when a cell reaches this stage?

Senescense (old age) - As enzymes decrease, there is loss of production of energy and deformability
When RBCs are no longer able to traverse the microvasculature, they are phagocytized by the RES cells

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What is the most common pathway an RBC uses to make energy?

What type of pathway is it? (aerobic/anaerobic)

Embden-Meyerhof pathway, generates 90% of RBC energy through breakdown of glucose
An anerobic pathway

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How many phases are involved in anaerobic glycolysis?

Three

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Embden-Meyerhof pathway:

What is the first step in phase one of anaerobic glucose catabolism? Substrate -> Enzyme -> Product

~ Glucose, ATP -> Hexokinase -> G6P, ADP

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Embden-Meyerhof pathway:

What is the second step in phase one of anaerobic glucose catabolism? Substrate -> Enzyme -> Product

~ G6P -> Glucose phosphate isomerase -> F6P

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Embden-Meyerhof pathway:

What is the third step in phase one of anaerobic glucose catabolism? Substrate -> Enzyme -> Product

~ F6P, ATP -> Phosphofructokinase -> F-1,6-P & ADP

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Embden-Meyerhof pathway:

What is the last step in phase one of anaerobic glucose catabolism? Substrate -> Enzyme -> Product

~ F-1,6-P -> Fructodiphosphate adolase -> DHAP, G3P

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Embden-Meyerhof pathway:

What is the first step in phase two of anaerobic glucose catabolism? Substrate -> Enzyme -> Product

~ G3P -> Glyceraldehyde-3-phosphate dehydrogenase -> 1,3-BPG

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Embden-Meyerhof pathway:

What is the second step in phase two of anaerobic glucose catabolism? Substrate -> Enzyme -> Product

~ 1,3-BPG, ADP -> Phosphoglycerate kinase -> 3-PG, ATP

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Embden-Meyerhof pathway:

What is the third step in phase two of anaerobic glucose catabolism? Substrate -> Enzyme -> Product

~ 1,3-BPG -> Bisphosphoglyceromutase -> 2,3-BPG

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Embden-Meyerhof pathway:

What is the last step in phase two of anaerobic glucose catabolism? Substrate -> Enzyme -> Product

~ 2,3-BPG -> Bisphosphoglycerate phosphatase -> 3-PG

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Embden-Meyerhof pathway:

What is the first step in phase three of anaerobic glucose catabolism? Substrate -> Enzyme -> Product

~ 3-PG -> Monophosphoglyceromutase -> 2-PG

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Embden-Meyerhof pathway:

What is the second step in phase three of anaerobic glucose catabolism? Substrate -> Enzyme -> Product

~ 2-PG -> Phosphopyruvate hydratase (enolase) -> PEP

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Embden-Meyerhof pathway:

What is the last step in phase three of anaerobic glucose catabolism? Substrate -> Enzyme -> Product

~ PEP, ADP -> Pyruvate kinase -> Pyruvate, ATP

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Embden-Meyerhof pathway:
How much ATP does the pathway generate?
How much of the overall energy for an RBC is obtained from this pathway?

Generates 2 molecules of ATP

- 90% energy is obtained via this pathway

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How does the Hexose monophosphate shunt protect RBCs?

Protects RBCs from environmental oxidants by detoxifying accumulated peroxide

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How much of the cells’ glucose is utilized to power the Hexose monophosphate shunt?
Is it done aerobically or anaerobically?

5-10% of glucose utilization

- done aerobically

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What is the most common RBC enzyme deficiency?

What pathway is this enzyme prominent in?

Glucose-6-phosphate dehydrogenase

- Hexose monophosphate pathway

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What role does the Hexose Monophosphate Pathway play in RBC energy generation?

Diverts glucose-6-phosphate (G6P) to pentose phosphate (PP) by the action of glucose-6- phosphate dehydrogenase (G6PD).
In the process, nicotinamide adenine dinucleotide phosphate (NADP) is reduced to NADPH.
NADPH is then available to reduce glutathione disulfide (GSSG) to glutathione (GSH).

What is the main function of the Methemoglobin Reductase Pathway?
Why is this function crucial to the RBC/patient?

Maintains iron in the ferrous (Fe2+) state

- If iron is in the ferric (Fe3+) state, it can’t bind and carry oxygen

Methemoglobin Reductase Pathway:

What causes iron to go from ferrous to ferric states?
What is a product of the changing iron states?

Heme iron is constantly exposed to oxygen, an oxidizing agent.
Methemoglobin results from the oxidation of heme iron from the ferrous to the ferric state

How does the Methemoglobin Reductase Pathway keep iron in the ferrous state? What enzyme is necessary for the reaction?

- Initiates reduction of methemoglobin by NADPH | - Reaction is more efficient in the presence of methemoglobin reductase.

What is the role of the Rapaport-Luebering pathway?

- Synthesis of 2,3-bisphosphoglycerate (2,3-BPG, also called 2,3, DPG)

Why is 2,3-bisphosphoglycerate (2,3-BPG, also called 2,3, DPG) so important?

- Regulates oxygen delivery to the tissues

Regulation of Metabolism: | What does hexokinase activity regulate (3)?

- G6P - 2,3-BPG - Hydrogen ions

Regulation of Metabolism: | What does phosphofructokinase activity regulate (3)?

- Adenosine triphosphate (ATP) - 2,3-BPG - Hydrogen ions

Regulation of Metabolism: | What does G6PD activity regulate (1)?

- NADPH

Regulation of Metabolism: | What does 2,3-BPG activity regulate (5)?

- Diphosphoglycerate mutase - 3-PGA and 2-PGA - 2,3-BPG - Phosphate ions - Hydrogen ions

Define RBC deformability.

- The ability for RBCs to stretch/change shape to fit through narrow spaces undamaged - Primarily through capilllaries and splenic pores

Osmotic Balance and Permeability of the cell membrane: - Define selective permeability. - What are examples of permeable substances? - What are examples of impermeable substances?

- Definition – RBC membrane permeable to some substances and impermeable to others - Permeable substances-water, HCO3- and Cl- - Impermeable to Na+, K+ and Ca2+

Osmotic Balance and Permeability of the cell membrane: - What is the function of the cation pump? - What are the concentrations of electrolytes the pump maintains?

- Regulates the concentrations of the ions Na+ and K+ - Concentrations Intracellular to extracellular: Na+ = 1:12 K+ = 25:1

What happens to the RBCs when the cation pump is damaged?

- If the cation pump is damaged, there will be influx of Na+ with water following; the cell swells and ruptures. (spherocytes) - Cell rupture allows release of K+ into the plasma = hemolysis

What is the role of Ca2+ ATPase?

- It extrudes calcium to maintain very low levels of intracellular calcium.

What effect does sickle-cell anemia have on membrane permeability? What does it do to the cells/electrolytes?

- SCA causes increased cation permeability | - Increased levels of Na+, K+ and Ca2+ exchange result in hemolysis

RBC Membrane Composition | - What are the three elements and their ratios that comprise the the membrane?

- Carbs - 8% - Proteins - 52% - Lipids - 40%

RBC Membrane composition: - What are the two main properties of the lipid bilayer? - What is the composition of the bilayer (3)?

- Hydrophilic properties (water loving) - Hydrophobic properties (water hating) - Composition: -- Cholesterol -- Phospholipids -- Glycolipids

What is a feature of the membrane cholesterol?

- RBC membrane cholesterol is in continual exchange with plasma cholesterol

What is the most abundant transmembranous protein?

- Band 3

How are the transmembranous proteins grouped?

- The transmembranous proteins assemble in one of two complexes defined by their anchorage to skeletal proteins ankyrin and 4.1

How does the transmembranous protein complex ankyrin work?

- In the ankyrin complex band 3 and protein 4.2 anchor to ankyrin, which is bound to the spectrin backbone

How does the transmembranous protein complex 4.1 work?

- Band 3, Rh, and other transmembranous proteins bind the complex of dematin, adducin, actin, tropomyosin, and tropomodulin through protein 4.1.

How many major and minor proteins are in the cell membrane? | What are two of the most important proteins in the cell membrane?

- 10 major and over 200 minor proteins in the membrane - Glycophorin, an integral protein - Spectrin, a peripheral protein

What are some of the functions and types of cell membrane proteins?

- Function- transport and adhesion sites, transport receptors - Integral proteins - Peripheral proteins (also called skeletal proteins)

Integral versus Peripheral Proteins: | - Differentiate

- Integral Proteins - - Extend from outer surface through the lipid bilayer - Peripheral Proteins - - Do not penetrate the lipid bilayer - - Line the inner membrane surface to form the membrane cytoskeleton

Membrane Composition: | What are three types of integral proteins?

- Glycophorins - Protein 3 - Rh blood group antigens

Membrane Composition: | What are five types of peripheral proteins?

- Spectrin (bands 1 and 2) - Actin (band 5) - Protein (band 4.1) - Ankyrin (bands 2.2, 2.3, and 2.6) - G3PD (band 6)

Glycophorin versus Spectrin: | - Functions

- Glycophorin (integral) - - Accounts for most of the membrane sialic acid …gives RBC its negative charge - - Location of many RBC antigens - Spectrin (peripheral) - - Strengthens membrane → shape and stability - - Preserves deformability (pliability)

Examples of a Structural Membrane Defect: | - What does accumulation of cholesterol in the RBC membrane do/look like?

- liver disease - - increases cell surface area - - decreases intracellular hemoglobin - - see target cells on a peripheral blood smear

Examples of a Structural Membrane Defect: | - What is abetalipoproteinemia?

- a rare autosomal recessive disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food - deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively - see acanthocytes (spiked cell membrane) on a blood smear

What are bite cells and why do they occur?

- RBCs that look like they have had a "bite" taken out of them - occur due to decreased spectrin = decreased pliablity. - - Decreased pliability makes it harder to pass through the spleen, so the macrophages there try to phagocytize the "sluggish" cells