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Hematology 1 and Body Fluids > RBC Metabolism and Membrane > Flashcards

RBC Metabolism and Membrane Flashcards

1
Q

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

A
  • Hexose monophosphate
  • Methhemoglobin reductase
  • Rapaport-Luebering
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2
Q

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

A
  • RBC metabolic pathways
  • RBC membrane
  • Hemoglobin structure and function
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3
Q

What is the reason behind hemolytic anemias?

A
  • Defects in one of the three areas of RBC metabolism
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4
Q

What is RBC senescense?

What happens when a cell reaches this stage?

A
  • 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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5
Q

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

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

A
  • Embden-Meyerhof pathway, generates 90% of RBC energy through breakdown of glucose
  • An anerobic pathway
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6
Q

How many phases are involved in anaerobic glycolysis?

A
  • Three
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7
Q

Embden-Meyerhof pathway:

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

A

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

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8
Q

Embden-Meyerhof pathway:

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

A

~ G6P -> Glucose phosphate isomerase -> F6P

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9
Q

Embden-Meyerhof pathway:

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

A

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

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10
Q

Embden-Meyerhof pathway:

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

A

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

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11
Q

Embden-Meyerhof pathway:

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

A

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

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12
Q

Embden-Meyerhof pathway:

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

A

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

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13
Q

Embden-Meyerhof pathway:

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

A

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

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14
Q

Embden-Meyerhof pathway:

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

A

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

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15
Q

Embden-Meyerhof pathway:

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

A

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

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16
Q

Embden-Meyerhof pathway:

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

A

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

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17
Q

Embden-Meyerhof pathway:

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

A

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

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18
Q

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

A
  • Generates 2 molecules of ATP

- 90% energy is obtained via this pathway

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19
Q

How does the Hexose monophosphate shunt protect RBCs?

A
  • Protects RBCs from environmental oxidants by detoxifying accumulated peroxide
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20
Q

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

A
  • 5-10% of glucose utilization

- done aerobically

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21
Q

What is the most common RBC enzyme deficiency?

What pathway is this enzyme prominent in?

A
  • Glucose-6-phosphate dehydrogenase

- Hexose monophosphate pathway

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22
Q

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

A
  • 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).
23
Q

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

A
  • Maintains iron in the ferrous (Fe2+) state

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

24
Q

Methemoglobin Reductase Pathway:

  • What causes iron to go from ferrous to ferric states?
  • What is a product of the changing iron states?
A
  • 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
25
Q

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

A
  • Initiates reduction of methemoglobin by NADPH

- Reaction is more efficient in the presence of methemoglobin reductase.

26
Q

What is the role of the Rapaport-Luebering pathway?

A
  • Synthesis of 2,3-bisphosphoglycerate (2,3-BPG, also called 2,3, DPG)
27
Q

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

A
  • Regulates oxygen delivery to the tissues
28
Q

Regulation of Metabolism:

What does hexokinase activity regulate (3)?

A
  • G6P
  • 2,3-BPG
  • Hydrogen ions
29
Q

Regulation of Metabolism:

What does phosphofructokinase activity regulate (3)?

A
  • Adenosine triphosphate (ATP)
  • 2,3-BPG
  • Hydrogen ions
30
Q

Regulation of Metabolism:

What does G6PD activity regulate (1)?

A
  • NADPH
31
Q

Regulation of Metabolism:

What does 2,3-BPG activity regulate (5)?

A
  • Diphosphoglycerate mutase
  • 3-PGA and 2-PGA
  • 2,3-BPG
  • Phosphate ions
  • Hydrogen ions
32
Q

Define RBC deformability.

A
  • The ability for RBCs to stretch/change shape to fit through narrow spaces undamaged
  • Primarily through capilllaries and splenic pores
33
Q

Osmotic Balance and Permeability of the cell membrane:

  • Define selective permeability.
  • What are examples of permeable substances?
  • What are examples of impermeable substances?
A
  • Definition – RBC membrane permeable to some substances and impermeable to others
  • Permeable substances-water, HCO3- and Cl-
  • Impermeable to Na+, K+ and Ca2+
34
Q

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?
A
  • Regulates the concentrations of the ions Na+ and K+
  • Concentrations
    Intracellular to extracellular:
    Na+ = 1:12
    K+ = 25:1
35
Q

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

A
  • 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
36
Q

What is the role of Ca2+ ATPase?

A
  • It extrudes calcium to maintain very low levels of intracellular calcium.
37
Q

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

A
  • SCA causes increased cation permeability

- Increased levels of Na+, K+ and Ca2+ exchange result in hemolysis

38
Q

RBC Membrane Composition

- What are the three elements and their ratios that comprise the the membrane?

A
  • Carbs - 8%
  • Proteins - 52%
  • Lipids - 40%
39
Q

RBC Membrane composition:

  • What are the two main properties of the lipid bilayer?
  • What is the composition of the bilayer (3)?
A
  • Hydrophilic properties (water loving)
  • Hydrophobic properties
    (water hating)
  • Composition:
    – Cholesterol
    – Phospholipids
    – Glycolipids
40
Q

What is a feature of the membrane cholesterol?

A
  • RBC membrane cholesterol is in continual exchange with plasma cholesterol
41
Q

What is the most abundant transmembranous protein?

A
  • Band 3
42
Q

How are the transmembranous proteins grouped?

A
  • The transmembranous proteins assemble in one of two complexes defined by their anchorage to skeletal proteins ankyrin and 4.1
43
Q

How does the transmembranous protein complex ankyrin work?

A
  • In the ankyrin complex band 3 and protein 4.2 anchor to ankyrin, which is bound to the spectrin backbone
44
Q

How does the transmembranous protein complex 4.1 work?

A
  • Band 3, Rh, and other transmembranous proteins bind the complex of dematin, adducin, actin, tropomyosin, and tropomodulin through protein 4.1.
45
Q

How many major and minor proteins are in the cell membrane?

What are two of the most important proteins in the cell membrane?

A
  • 10 major and over 200 minor proteins in the membrane
  • Glycophorin, an integral protein
  • Spectrin, a peripheral protein
46
Q

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

A
  • Function- transport and adhesion sites, transport receptors
  • Integral proteins
  • Peripheral proteins (also called skeletal proteins)
47
Q

Integral versus Peripheral Proteins:

- Differentiate

A
  • 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
48
Q

Membrane Composition:

What are three types of integral proteins?

A
  • Glycophorins
  • Protein 3
  • Rh blood group antigens
49
Q

Membrane Composition:

What are five types of peripheral proteins?

A
  • Spectrin (bands 1 and 2)
  • Actin (band 5)
  • Protein (band 4.1)
  • Ankyrin (bands 2.2, 2.3, and 2.6)
  • G3PD (band 6)
50
Q

Glycophorin versus Spectrin:

- Functions

A
  • 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)
51
Q

Examples of a Structural Membrane Defect:

- What does accumulation of cholesterol in the RBC membrane do/look like?

A
  • liver disease
    • increases cell surface area
    • decreases intracellular hemoglobin
    • see target cells on a peripheral blood smear
52
Q

Examples of a Structural Membrane Defect:

- What is abetalipoproteinemia?

A
  • 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
53
Q

What are bite cells and why do they occur?

A
  • 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

Hematology 1 and Body Fluids (9 decks)

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