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Department of Biochemistry
Faculty of Medicine UNHAS
Biomedical Science 2
Makassar, 9thMarch 2011
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Introduction
Plasma proteins Membrane of erythrocytes
Structure and function of Hemoglobin
Metabolism of Erythrocytes
Metabolism of LeukocytesClinical correlations
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Human blood constitutes about 8% of the
bodysweight
Consists of cellsand cell fragments in anaqueous medium, the blood plasma
The proportion of cellular elements, known
as hematocrit, in the total volume isapproximately 45%
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The blood plasma is an aqueous solution
of electrolytes, nutrients, metabolites,
proteins, vitamins, trace elements, andsignaling substances
The fluid phase of coagulated blood is
known as blood serum It differs from the plasma in that it lacks
fibrin and other coagulation proteins
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Quantitatively, proteinsare the most
important partof the soluble components
of the blood plasmaWith concentrations of between 60 and 80
g/L, they constitute approximately 4% of
the bodys total protein
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Some 100 different proteins occur in
human blood plasma.
Based on their behavior duringelectrophoresis they are broadly dividedinto five fractions: albuminsand 1, 2,
and-globulins
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Under the microscope, the red blood cell appears
to be a red disc with a pale central area (biconcave
disc)
The biconcave disc shape serves to facilitate gasexchange across the cell membrane
The membrane proteins: maintain the shape of the red blood cell
allow the red blood cell to traverse the capillaries with very
small luminal diameters to deliver oxygen to the tissues
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The interior diameters of many capillariesare smaller than the approximately 7.5m
diameter of the red cell
The spleen is the organ responsible for
determining the viability of the red blood
cells
Erythrocytes pass through the spleen 120times per day
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The elliptical passageways through thespleen are approximately 3m in diameter,
and normal red cells traverse them in
approximately 30 seconds
Damaged red cells that are no longer
deformable become trapped in the
passages in the spleen, where they aredestroyed by macrophages
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On the cytoplasmic side of the membrane,
proteins form a two-dimensional lattice that
gives the red cell its flexibility
The major proteins are spectrin, actin,
band 4.1, band 4.2, and ankyrin.
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The most important task of the red blood
cells (erythrocytes) is to transport
molecular oxygen (O2) from the lungs intothe tissues, and carbon dioxide (CO2) from
the tissues back into the lungs
To achieve this, the higher organisms
require a special transport system, since
O2 is poorly soluble in water
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Only around 3.2 mL O2 is soluble in 1 L
blood plasma. By contrast, the protein
hemoglobin (Hb), contained in theerythrocytes, can bind a maximum of 220
mL O2 per liter70 times the physically
soluble amountThe Hb content of blood:
140180 g/L in men
120160 g/L in women
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Adult hemoglobin is a tetrameric
hemeprotein (quartenery structure) found
in erythrocytes where it is responsible for
binding oxygen in the lung andtransporting the bound oxygen throughout
the body where it is used in aerobic
metabolic pathwaysThe tetramers are composed of pairs of
two different polypeptide subunits
The subunits are -, -, -, -chain
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The haemoglobin molecule is a tetramer consisting of 4 polypeptide
chains, known as globins, which are usually:
2 alpha chains that are each 141 amino acids long
2 beta chains that are each 146 amino acids long
Attached to each chain is an iron-containing molecule known as haem
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Adult hemoglobin is a tetrameric hemeprotein(HbA1, 22, 97%), (HbA2, 22, 2-3%)
Two other forms occur during embryonic and
fetal development the first three months, embryonic hemoglobins
are formed, with the 22and 22
up to the time of birth, fetal hemoglobin then
predominates (HbF, 22)
during the first few months of life, it is replaced
gradually by HbA
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Oxygenated dan Deoksigenated Hemoglobin The subunit of deoxyhemoglobin are held
together by salt bonds between the
polypeptide Upon oxygenation the salt bonds break
and a new set of hydrogen bonds form
The interactions between the subunits areweaker in oxyhemoglobin than in
deoxyhemoglobin
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Methemoglobin
The heme iron is ferric rather than ferrous Can neither bind nor transport O2
Normally, the enzyme methemoglobin reductasereduces the Fe3+of methemoglobin to Fe2+
Methemoglobin can arise by oxidation of Fe2+to
Fe3+as a side effect of agents such as
sulfonamides, from hereditary hemoglobin M, orconsequent to reduced activity of the enzyme
methemoglobin reductase
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Erythrocytes can only generate adenosine
triphosphate (ATP) by glycolysis
The ATP is used for:
ion transport across the cell membrane (primarilyNa+, K+, and Ca2+)
the phosphorylation of membrane proteins
the priming reactions of glycolysis
Erythrocyte glycolysis also uses the
Rapaport-Luebering shunt to generate 2,3-
bisphosphoglycerate (2,3-BPG).
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The Respiratory Burst
When neutrophils and other phagocytic cellsengulf bacteria, they exhibit a rapid increase
in oxygen consumption known as the
respiratory burst
This phenomenon reflects the rapid utilization
of oxygen and production from it of large
amounts of reactive derivatives, such as
O2, H2O2, OH, and OCl(hypochlorite
ion)
Some of these products are potent icrobicidal
agents.
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The mutated
hemoglobin tends to
aggregate in the
deoxygenated form
This leads to sickle-
shaped distortion of the
erythrocytes anddisturbances
of O2 transport (sickle-
cell anemia)
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