Biochemistry of Blood Elements

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The figure is found at http://www.biosbcc.net/doohan/sample/htm/Blood%20cells.htm (March 2007)

Blood Elements Count

erythrocytes

4 - 6 x 106 / l

leukocytes

4 - 9 x 103 / l

neutrophils
eosinophils
basophils
lymphocytes
monocytes

47 - 75 %
1 - 4 %
0 - 1 %
23 - 45 %
2 - 11 %

thrombocytes

150 - 400 x 103 / l

Red Blood Cells

(erythrocytes)

The figure is found at http://www.vghtpe.gov.tw/~hema/hematopoitic%20cell%20differentiation/RBC.htm (March 2007)

Red Blood Cells

(erythrocytes)

Erythrocytes in mammals are anucleate

when mature, meaning that they lack a cell
nucleus and as a result, have no DNA
Red blood cells have nuclei during early
phases of development, but extrude them as
they mature in order to provide more space
for hemoglobin
Mammalian erythrocytes also lose their
other organelles such as their mitochondria

Red Blood Cells

(erythrocytes)

As a result, red blood use none of the oxygen they

transport; they produce the energy carrier ATP by
fermentation, via glycolysis of glucose followed by
lactic acid production
Furthermore, red cells do not have an insulin
receptor and thus glucose uptake is not regulated by
insulin
Because of the lack of nucleus and organelles, the red
blood cells cannot synthesize any RNA, and
consequently they cannot divide or repair
themselves

Red Blood Cells

(erythrocytes)

Adult humans have roughly 23 1013 red blood

cells at any given time
Women have about 4 to 5 million erythrocytes per
microliter of blood
Men about 5 to 6 million per microliter of blood
People living at high altitudes with low oxygen
tension will have more red blood cells
There are about 4,00011,000 white blood cells
and about 150,000400,000 platelets in each
microliter of human blood

Red Blood Cells

(erythrocytes)

1. Function

erythrocyte as a bag for hemoglobin

O2 transport, reactive oxygen species (ROS)

CO2 transport, formation of HCO3-

H+ transport, maintaining pH

(35% of blood buffering capacity)

Red Blood Cells

(erythrocytes)

2. Structure

large surface
(diffusion of gases)

cytoskeletal proteins
(elasticity)

membrane as an osmometer
(Na+/K+-ATPase)

This shape optimizes the cell for the

exchange of oxygen with its surroundings
The cells are flexible so as to fit through
tiny capillaries, where they release their
oxygen load
The figure is found at http://www.biosbcc.net/doohan/sample/htm/Blood%20cells.htm (March 2007)

What happens to red blood cells when placed in

hypotonic, hypertonic, and isotonic solutions?

osmolarity

(285 mosmol/l)

acanthocytes

hemolysis
(blood, plasma)

The figure is found at http://www.vet.purdue.edu/depts/bms/nour/bms520/content/blood/b9.htm (March 2007)

Red Blood Cells

Sickle cell Disease

(erythrocytes)

membrane and
cytoskeletal
proteins

hereditary spherocytosis

The figures are found at http://www.wadsworth.org/chemheme/heme/microscope/pix/spherocytes_nw.jpg and

http://www.mie.utoronto.ca/labs/lcdlab/biopic/fig/4.23b.jpg (March 2007)

Red Blood Cells

(erythrocytes)

3. membrane transporters
Na+/K+-ATPase (active transport)
GLUT-1 (insulin independent)
anion exchanger = band 3 protein (Cl-/HCO3-)

4. membrane antigens
blood groups

Red Blood Cells

(erythrocytes)

5. metabolism
glucose is the main fuel
90% anaerobic glycolysis
(ATP, lactate: Cori cycle; 2,3-BPG)
10% hexose monophosphate pathway
(NADPH)
enzyme defects :

* glucose-6-P dehydrogenase
* pyruvate kinase

hemolytic anemia

Red Blood Cells

(erythrocytes)

Anaerobic glycolysis (lactate formation) is

the only one source of ATP! (Why??)
2,3 BPG shunt is unique for RBC

Biosynthesis of 2,3Bisphosphoglycerate
Note that when
glucose is oxidized by
this pathway the RBC
loses the ability to
gain 2 moles of ATP
from glycolytic
oxidation of 1,3-BPG
to 3-PG via the
phosphoglycerate
kinase reaction
15

Biosynthesis of 2,3Bisphosphoglycerate
The compound 2,3bisphosphoglycerate
(2,3-BPG), derived
from the glycolytic
intermediate 1,3bisphosphoglycerate,
is a potent allosteric
effector on the oxygen
binding properties of
hemoglobin

Biosynthesis of 2,3Bisphosphoglycerate
In the deoxygenated T conformer, a cavity capable of
binding 2,3-BPG forms in the center of the molecule
2,3-BPG can occupy this cavity stabilizing the T state
Conversely, when 2,3-BPG is not available, or not
bound in the central cavity, Hb can be converted to
HbO2 (R) state more readily
Thus, like increased hydrogen ion concentration,
increased 2,3-BPG concentration favors conversion
of R form Hb to T form Hb and decreases the amount
of oxygen bound by Hb at any oxygen concentration

Red Blood Cells

(erythrocytes)

5. other important enzymes

carbonate dehydratase (= carbonic anhydrase, CA)
methemoglobin reductase
superoxide dismutase
catalase
glutathione peroxidase
glutathione reductase

antioxidative system

Carbonic Anhidrase

Red Blood Cells

(erythrocytes)

superoxide dismutase (SOD)

O2 + O2 + 2 H+ H2O2 + O2
catalase (CAT)
H2O2 + H2O2 2 H2O + O2

Red Blood Cells

(erythrocytes)

glutathione peroxidase (GPx)

2 GSH + H2O2

GS-SG + 2 H2O

2 GSH + R-O-OH GS-SG + H2O + ROH

glutathione = redox buffer

The figure is found at

http://www.cs.stedwards.edu/chem/Chemistry/CHEM47/Res
Methods2003/graphics/?M=A

glutathione reductase
GS-SG + NADPH+H+
2 GSH + NADP+

Hexose Monophosphate
Pathway

The figure is found at http://www.med.unibs.it/~marchesi/ppp.html (March 2007)

Glutathione system

NADPH+H+

The figure is found at http://www.vrp.com/newsimages/march04Fig1.jpg (March 2007)

Red Blood Cells

(erythrocytes)

High tension of oxygen

GSH as a defense against harmful oxygen
radicals
Inactivation of O is coupled with GSH
oxidation, back reduction need NADPH
NADPH + GSSG = NADP + GSH
Pentose phosphate pathway is a source of
NADPH
Glc-6-P deficiency hemolytic anemia

Red Blood Cells

(erythrocytes)

6. Erythropoesis

The figure is found at http://www.biosbcc.net/doohan/sample/htm/Blood%20cells.htm (March 2007)

Red Blood Cells

(erythrocytes)

The process by which red blood cells are produced is

called erythropoiesis
Erythrocytes are continuously being produced in the
red bone marrow of large bones, at a rate of about
tow million per second
The production can be stimulated by the hormone
erythropoietin (EPO), synthesized by the kidney;
which is used for doping in sports
Erythrocytes develop from committed stem cells
through reticulocytes to mature erythrocytes in about 7
days and live a total of about 120 days

White Blood Cells

(leukocytes)

The figure is found at http://faculty.ccp.edu/dept/biol/All_five_leukocytes.jpg (March 2007)

White Blood Cells

(leukocytes)

Classification
granulocytes
neutrophils (phagocytosis)
eosinophils (alergy, parasites)
basophils (alergy)

agranulocytes
monocytes macrophages
lymphocytes (B, T)

Reactive oxygen and nitrogen species

in blood elements
ERYTHROCYTES
enzymes for deactivation of ROS formed
from high content of oxygen found in the
cells
PHAGOCYTES
enzymes for production of ROS and RNS to
destroy particles in phagosomes

White Blood Cells

(leukocytes)

Neutrophils (microphages)
high content of lysosoms (hydrolytic enzymes)
few mitochondria
glucose dependent: NADPH production
NADPH is used for production of reactive
oxygen species they kill bacteria
after activation: RESPIRATORY BURST
= increased consumption of O2 and glucose

Reactive oxygen species (ROS)

produced by neutrophils

ClOThe figure is found at http://courses.washington.edu/conj/bloodcells/radicals.gif (March 2007)

White Blood Cells

(leukocytes)

proteolytic enzymes /
elastase
collagenase
gelatinase
kathepsin G

produced by phagocytes

protease inhibitors
1-protease inhibitor
(= 1-antitrypsin)
1-antichymotrypsin
2-macroglobulin

= plasma proteins

Their ratio affects an extent of inflammation!

Basofils
contain heparin and histamine

The figures are found at http://life.nthu.edu.tw/~lslpc/BioPhyTalk/heparin01.jpg and

http://www.nottingham.ac.uk/~mqzwww/images/histamine.gif (March 2007)

B-lymphocytes
produce antibodies (= immunoglobulins, -globulins)

( or )

(, , , , )
The figure is found at http://www-immuno.path.cam.ac.uk/~immuno/part1/lec06/ab12.gif (March 2007)

Platelets

(thrombocytes)

The figure is found at http://image.bloodline.net/stories/storyReader$590 (March 2007)

Platelets

(thrombocytes)
participate in hemostasis

adhesion: glycosaminoglycans and glycoproteins (hyalomera)

activation: free collagen, thrombin, ADP, TxA2, serotonin
contraction of thrombus: Ca2+, glycogen, ATP
The figure is found at http://www.biosbcc.net/doohan/sample/htm/Hemostasis.htm (March 2007)