1. Mammalian Transport System
Ch. 8 Part 3 Hemoglobin and Bohr Shift

2. Haemoglobin Globular protein 4 polypeptide chains
Haem group on each polypeptide chain (prosthetic group); each with iron atom
4 iron atoms in 1 haemoglobin = 4 O2 molecules (total of 8 oxygen atoms per haemoglobin)
Hb + 4 O2 --><-- Hb O8

3. How Oxygen is Transported in Blood
Dissolved oxygen in plasma
Oxyhemoglobin (HbO2)

4. Partial Pressure = concentration
Haemoglobin
Partial Pressure = concentration
Picks up AND drops off oxygen
Things to understand:
Partial pressures of oxygen
Different concentrations of oxygen gas
Saturation
When a sample of haemoglobin is combined with its maximum amount of oxygen (100%)
When identical samples of haemoglobin are used with lower concentrations of oxygen (lower partial pressure), then amount of oxygen-haemoglobin combinations will be a percentage of 100

5. Dissociation Curve
When the percentage saturation of each haemoglobin sample is plotted against the partial pressure of oxygen
Partial pressure of oxygen = different concentrations of oxygen
High partial pressure = lots of oxygen
Low partial pressure = less oxygen
kPa is used to measure partial pressure of oxygen

7. DESCRIBING the Haemoglobin Dissociation Curve
Shows:
At low partial pressure of O2, % saturation of haemoglobin is very low
At high partial pressure of O2. % saturation of haemoglobin is very high

8. Differences in Saturation
Haemoglobin in capillary
Lots of oxygen (high partial pressure)
Lots haemglobin-oxygen combinations
High saturation 95-97%
Haemoglobin in RBC at respiring tissue
Less oxygen available (b/c cells are using it) LOW partial pressure
Less haemglobin-oxygen combinations
Low saturation 20-25%

10. EXPLAINING the Haemoglobin Dissociation Curve
Explain behavior of haemoglobin and oxygen molecules
Oxygen atoms combine with Fe atoms in the haem group of each of the 4 polypeptide chains in haemoglobin
When 1 oxygen molecule combines with 1 iron atom in 1 haem group, entire haemoglobin molecule becomes distorted (conformation change!)
Makes it easier for 2nd oxygen Molecule to attach to 2nd iron atom in 2nd haem group
Makes it easier for 3nd oxygen Molecule to attach to 3nd iron atom in 3nd haem groups
Very easy for 4th oxygen molecule to attach to iron in the last haem group
COOPERTIVITY!

11. Analyzing the dissociation curve
Small change in partial pressure causes large change in saturation of haemoglobin with oxygen
Curve rises steeply
once oxygen molecules begin attaching to haemoglobin, it becomes easier for successive oxygens to attach
“Coopertivity”

12. Factors that effect haemoglobins ability to carry oxygen
Partial Pressure of oxygen
High partial pressure = haemoglobin picks up oxygen (makes HbO2)
Low partial pressure = haemoglobin releases oxygen
Partial pressure of carbon dioxide
High partial pressure of CO2 = haemoglobin releases oxygen
Low partial pressure of CO2 = haemoglobin picks up oxygen

13. Think about where in the body we would have these different conditions
Reasons for O2 Delivery
Low partial pressure of oxygen (O2)
Diffusion of O2 from high concentration to low concentration
Hydrogen ions (H+) compete with O2 for Hb
DECREASED pH
CO2 competes with O2 for Hb
Think about where in the body we would have these different conditions
Reasons for CO2 Delivery
Low partial pressure of carbon dioxide (CO2)
Diffusion of CO2 from high concentration to low concentration
Oxygen (O2) competes with H+ ions and CO2 for Hb

14. 3 ways of CO2 transport As Hydrogencarbonate ion HCO3- (85%)
Made in cytoplasm by dissociation of carbonic acid Ions diffuse out of RBC into plasma
2. As Carbamino-haemoglobin (10%)
When CO2 molecules that diffused in RBC didn’t undergo carbonic anhydrase reaction
CO2 combines w/terminal amine group of polypeptide chain in haemoglobin
As Carbon Dioxide gas CO2 (5%)
Diffuse back into blood plasma

15. When CO2 diffuses into the RBC
CARBONIC ANHYDRASE
Catalyzes the formation of Carbonic acid by combining water and carbon dioxide
Carbonic acid dissociates into H+ ion and a hydrogen carbonate ion (HCO3-)
Hydrogen carbonate ion (bicarbonate) diffuses into plasma of blood and is carried to lungs
Haemoglobin prefers H+ ions, so it releases oxygen and picks up H+ ions (high AFFINITY for hydrogen ions)
Becomes haemoglobinic acid (HHb)
Haemoglobin CLEANS up RBC of H+ ions created from the dissociation of carbonic acid, preventing pH inside RBC from dropping
Haemoglobin acts BUFFER

16. Equations Carbon dioxide diffuses into RBC and immediately:
CO2 + H2O Carbonic anhydrase- H2CO3
Carbonic Acid then dissociates in aqueous cytoplasm of RBC…
H2CO3 <-----> H HCO3-
Increase of H+ ions would decrease pH (make it acidic) if it weren't for haemoglobin’s AFFINITY for H+ ions
Dumps oxygen and picks up H+
Carbonic acid
Hydrogen carbonate ion

17. CO2 carried as Carbamino-haemoglobin (10%)
When CO2 molecules that diffused in RBC didn’t undergo carbonic anhydrase reaction
CO2 combines DIRECTLY with terminal amine group of polypeptide chain in haemoglobin
Reaction causes release of hydrogen ion (H+)
CO2 + HbO2  HbCOO- + H+ + O2
H+ gets “mopped up” by hemoglobin (high affinity for H+)
HHb (hemoglobin carrying hydrogen ion)
O2 gets dropped off
Reverse reaction occurs once RBC and plasma get to the lung

18. CO2 / H+ are affecting he affinity of Hb for O2
Bohr Effect
When the presence of a high partial pressure of carbon dioxide causes haemoglobin to release oxygen
Lots of CO2 makes haemoglobin let go of oxygen atoms
Actively respiring cells (in active muscles) produces lots of CO2
CO2 diffuses from cell into blood plasma and then into RBC
Haemoglobin in RBC QUICKLY let go of oxygen to pick up H+ ions
HALDANE EFFECT
O2 is affecting the affinity of the Hb for CO2 / H+
BOHR EFFECT
CO2 / H+ are affecting he affinity of Hb for O2

22. Changing CO2 and O2 concentrations and the Dissociation Curve
Lungs
Partial pressure CO2 LOW
Partial pressure of O2 HIGH
Active tissues
Partial pressure of CO2 HIGH
Partial pressure of O2 LOW

23. RBCs travel through veins to lungs….
All reactions are reversed to release CO2 gas
Hydrogen carbonate ions change back into carbonic acid and back into carbon dioxide at lungs
Carbon dioxide dissociates from amine-group in hemoglobin and becomes carbon dioxide and diffuses out of blood and into lungs
Blood has a high partial pressure of CO2 than alveoli at lungs
CO2 diffuses down pressure gradient (RBCAlveoli)
Haemoglobin molecules free to pick up oxygen that is in high concentration (high partial pressure) in alveoli

24. CO2 / H+ are affecting he affinity of Hb for O2
Oxygen is transported by:
Dissolved O2
HbO2 (oxyhemoglobin)
OVERVIEW!
Tissue
Lungs
HbO2 + H+  HHb + O2
HbO2 + CO2  HbCoo- + H+ + O2
Carbon Dioxide is transported by:
Dissolved CO2
HHb (HCO3-)  CO2 + H2O
HbCOO- + H+  HHb
BOHR EFFECT
CO2 / H+ are affecting he affinity of Hb for O2
HALDANE EFFECT
O2 is affecting the affinity of the Hb for CO2 / H+

25. Problems with Oxygen Transport
Carbon Monoxide
High Altitude

26. Carbon Monoxide CO
Haemoglobin combines 250 times more readily AND irreversibly with CO (compared to oxygen)
If CO fumes are inhaled, they dissolve immediately through alveoli into blood, into RBCs
CO combines with haem groups (instead of oxygen) making CARBOXYHAEMOGLOBIN
SUPER stable compound = haem will NOT release CO
Low concentrations (0.1%) of CO in air = asphyxiation
CO poisoning treated with high concentration of Oxygen and carbon dioxide
Cigarette smoke  5% CO

27. High Altitude Sea level partial pressure of O2 = 20 pKa
Alveolar partial pressure of O2 = 13 pKa
Mountain (6500m) partial pressure of O2 = 10 pKa
Alveolar partial pressure of O2 = 5.3 pKa
Look at dissociation curve haemoglobin will only be 70% saturated
Less O2 means cells cannot make ATP efficiently fatigue, light-headedness, illness

28. Altitude Sickness
Causes: when someone travels from sea level to high altitude very quickly
Body does not have time to adjust to drop in O2 availability
Symptoms:
Increase in breathing rate
Increase in depth of breathing
Weakness
Dizziness
Disorientation:
Arterioles dilate  more blood rushing into capillaries (increase pressure at arteriole end of capillaries)  more fluid forced out of capillaries increased tissue fluid (especially bad in brain)  hallucinations, lightheadedness
Fluid leakage in lungs

29. Adaptation to High Altitude
Need to build tolerance to high altitude
Body acclimatizes to declining O2 levels
Red blood cell count increases
Normally make up 40-50% of blood
High altitude RBC make up 50-70%
Long time exposure (living in high altitude areas)
Increased RBC production
Increased lung capacity/broader chest
Increased amount of haemoglobin
Increased size in RIGHT side of heart (pumping blood to lung)
High altitude training