Transcript
Biochemistry of Blood Elements
The figure is found at http://www.biosbcc.net/doohan/sample/htm/Blood%20cells.htm (March 2007)
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Blood Elements Count
erythrocytes 4 - 6 x 106 / l
leukocytes 4 - 9 x 103 / l
neutrophils 47 - 75 %eosinophils 1 - 4 %basophils 0 - 1 %lymphocytes 23 - 45 %monocytes 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 2–3 × 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 4,000–11,000 white blood cells
and about 150,000–400,000 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)
The figure is found at http://www.vet.purdue.edu/depts/bms/nour/bms520/content/blood/b9.htm (March 2007)
• hemolysis(blood,
plasma)
What happens to red blood cells when placed in hypotonic, hypertonic, and
isotonic solutions?
• osmolarity(285 mosmol/l)
• acanthocytes
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)
membrane and cytoskeletal
proteins
hereditary spherocytosis
Sickle cell Disease
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 2,3-Bisphosphoglycerate
• 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
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Biosynthesis of 2,3-Bisphosphoglycerate
• The compound 2,3-bisphosphoglycerate (2,3-BPG), derived from the glycolytic intermediate 1,3-bisphosphoglycerate, is a potent allosteric effector on the oxygen binding properties of hemoglobin
Biosynthesis of 2,3-Bisphosphoglycerate
• 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 antioxidative
system glutathione peroxidase glutathione reductase
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
The figure is found at http://www.cs.stedwards.edu/chem/Chemistry/CHEM47/ResMethods2003/graphics/?M=A
(March 2007)
glutathione = „redox buffer“
The figure is found at http://www.med.unibs.it/~marchesi/ppp.html (March 2007)
Hexose Monophosphate
Pathway
glutathione reductaseGS-SG + NADPH+H+
2 GSH + NADP+
The figure is found at http://www.vrp.com/newsimages/march04Fig1.jpg (March 2007)
2
Glutathione system
NADPH+H+
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
The figure is found at http://www.biosbcc.net/doohan/sample/htm/Blood%20cells.htm (March 2007)
Red Blood Cells(erythrocytes)
6. Erythropoesis
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
The figure is found at http://faculty.ccp.edu/dept/biol/All_five_leukocytes.jpg (March 2007)
White Blood Cells
(leukocytes)
White Blood Cells(leukocytes)
Classification• granulocytes
neutrophils (phagocytosis)eosinophils (alergy, parasites)basophils (alergy)
• agranulocytesmonocytes → macrophages lymphocytes (B, T)
Reactive oxygen and nitrogen species
in blood elementsERYTHROCYTESenzymes for deactivation of ROS formed
from high content of oxygen found in the cells
PHAGOCYTESenzymes 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
The figure is found at http://courses.washington.edu/conj/bloodcells/radicals.gif (March 2007)
Reactive oxygen species (ROS)produced by neutrophils
ClO-
White Blood Cells(leukocytes)
proteolytic enzymes /elastasecollagenasegelatinasekathepsin G
protease inhibitors1-protease
inhibitor(= 1-antitrypsin)
1-antichymotrypsin2-macroglobulin
produced by phagocytes = plasma proteins
Their ratio affects an extent of inflammation!
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)
Basofilscontain heparin and
histamine
The figure is found at http://www-immuno.path.cam.ac.uk/~immuno/part1/lec06/ab12.gif (March 2007)
B-lymphocytesproduce antibodies (= immunoglobulins, -globulins)
( or )
(, , , , )
The figure is found at http://image.bloodline.net/stories/storyReader$590 (March 2007)
Platelets(thrombocytes
)
The figure is found at http://www.biosbcc.net/doohan/sample/htm/Hemostasis.htm (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
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