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Lecture 3

BIOC19H3 Lecture Notes - Lecture 3: Phosphatidylserine, Nucleated Red Blood Cell, Erythropoietin Receptor


Department
Biological Sciences
Course Code
BIOC19H3
Professor
Ian Brown
Lecture
3

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BIOC19
Sept 21, 2017
Lec 3
Development of red blood cells (Erythropoiesis)
Today, we will look at the differentiation of red blood cells as our first model system in Dev Biol
in the following sequence
1. Characteristics of mature red blood cells (RBCs)
2. Development of red blood cells (from stem cell to mature RBC)
3. Pathologies (diseases) of red blood cells (when normal RBC development goes wrong)
- Nucleus in final differentiated cell in Ave, Birds + fish -- > condense
- Final differentiated RBC circulating in body has no nucleus
- So specialized, shut nucleus down
- Humans expelled nucleus in final differentiated cell
- Extreme differentiated human final RBC no nucleus
- In other species birds, fish, amps circulating RBC has nucleus but highly condense
Shape of mature human RBC (called an erythrocyte)
Simple cells: no organelles, no nucleus, only plasma membrane, cytoskeleton and
cytoplasm, 95% of protein content is hemoglobin
Biconcave shape, nucleus lost during development of red blood cell
- Not sphere disc shaped, one side has concave depression
- Differentiated human RBC = simple cell bc if we look inside no organelles like
mitochondria or golgi in fully differentiated cell
- All specialized organelles gone
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Human erythrocytes (mature RBCs) are constantly spinning, tumbling, flexible and squeezing
through large and small blood vessels in all tissues of the body
- To do this to get through small blood cells, differentiated RBC has to be flexible has to
twist and turn without breaking
Cytoskeleton of erythrocytes
Actin (blobs in diagram at lower right) and spectin (rods in diagram) are 2 key proteins
that comprise the mesh-like cytoskeleton that gives the mature RBC its shape
This cytoskeleton mesh structure gives a flexible quality to erythrocytes (ability to bend
without breaking)
Erythrocyte cytoskeleton
The distribution of actin protein molecules in the mesh-like cytoskeletonal structure is
shown in GREEN
The distribution of spectrin protein molecules is shown in RED
Function of Erythrocytes
Key role in oxygen and carbon dioxide exchange:
RBCs transport O2 from lungs to body tissues and carry CO2 away
Why do cells need oxygen?
For cellular respiration:
C6H12O6 + 6O2 6CO2 + 6H2O + 36ATP
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How do erythrocytes (i.e. mature RBCs) transport oxygen?
- Hemoglobin molecule that transport oxygen
- Heme component bind oxygen
Hemoglobin
Each hemoglobin molecule consists of four globin protein subunits, associated with a
heme group
For adult hemoglobin the conformation is: 2α + 2β globin protein subunits, each globin
subunit having a molecular weight of 17kDa
Heme group iron-containing porphyrin ring
Iron atom can be in reduced (Fe2+) or oxidized (Fe3+) form
Each iron can bind one molecule of O2 when in reduced form.
The quaternary structure of hemoglobin is maintained via hydrogen bonds, salt bridges,
and hydrophobic bonds
How do erythrocytes obtain energy?
Principal metabolic pathway of erythrocytes: glycolysis in the RBC cytoplasm
Glycolysis: Glucose + 2 ADP + 2 NAD+ + 2 Pi -----> 2 Pyruvate + 2 ATP + 2 NADH + 2 H+
ATP is used as energy to maintain pumps in erythrocyte membrane, which helps
maintain shape and flexibility of the RBC
Reducing potential of NADH is needed to maintain iron in hemoglobin in its reduced
form (Fe2+) so that it can bind oxygen
Erythrocytes have a limited life span
Erythrocyte life span: ~120 days in circulating human blood
Removal of aged RBCs- 90% are engulfed by macrophages in spleen, liver and lymph
nodes
10% are damaged during circulation and hemolyze (break open). Resulting pieces are
engulfed by macrophages
What triggers erythrocyte removal by macrophages?
Subject is still debated, but the story so far:
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