Red Blood Cells Flashcards
Blood Gas Transport overview
Haemoglobin binds O2 in lungs (where PO2 is high) and unbinds it in tissues (where PO2 is low) Hb moves CO2 in opposite direction Cooperativity and chemical allosteric effects -> more O2 is bound in lungs and is deposited in tissues.
Characteristics of oxygen
- Poorly soluble in plasma – normal arterial blood carries 70X more O2 on Haemoglobin (Hb in RBCs) than dissolved directly in plasma
Hb is needed to carry O2
Thus, it is possible for arterial PO2 to be normal but hypoxia to occur (b/c there is no Hb to carry O2)
Why you need O2:
- Oxidative Respiration Produces More Energy
muscle: C6H12O6 + 6 O2 -> 6 CO2 + 6 H2O + ~36 ATP - In RBCs without mitochondria (anaerobic glycolysis):
C6H12O6 -> 2 lactate + 2 ATP
How is Hb able to deliver O2 to tissues?
Hb must bind O2 and also release
O2 binding must be weak enough to be reversible
the two mechanisms involved are - Cooperativity and “right shifting” of binding curve
Why do we need Oxygen
Oxidative respiration produces more energy
Haemoglobin characteristics
- 95% of dry weight of RBC
- Each subunit has a small haem group (616 Da) + a large globin peptide (17,000 Da)
- Haem is coloured, contains one Iron atom, and is site of O2 binding
- picks up oxygen in lungs and releases it in tissues
- haemoglobin has allosteric properties:
- cooperativity
Haem group
Each Haemoglobin and myoglobin subunit has 1 haem group
§ Haem carries O2
haem group
§ Haem is a porphyrin ring
§ They are rigid, 2 dimensional, and highly coloured due to sharing of electrons
- Hence red and blue colour
- Not due to Iron
conjugated to iron ion
§ Ferrous (Fe2+)
Explain Hb Cooperativity
§Each subunit can carry 1 O2 molecule on its haem
§Each subunit influences its 3 neighbours
§O2 binding —> more O2 binding
§O2 release —> more O2 release
Difference between Adult and child Hbs
Healthy Adults (HbA)
§2 alpha subunits + 2 beta subunits (4 subunits = tetramer)
§Also called “maternal Haemoglobin”
Foetal Haemoglobin (HbF)
§2 alpha subunits + 2 gamma subunits
§Adults have a small percentage of HbF
§Binds O2 more strongly than HbA
Explain the Bohr effect
the “Bohr effect”
↑ blood carbon dioxide level —> ↓ affinity of Hb for O2
↓ blood pH —> ↑ affinity of Hb for O2
b/c of carbonic anhydrase rxn
↑ blood carbon dioxide level —> ↓ blood pH
CO2 & H+ bind Hb but at a different site from O2
Outline the three ways CO2 is carried in blood
A) 10% as dissolved, B) 22% as carbamino, C) 68% as HCO3-
Oxygen binding by myoglobin and haemoglobin curve
Sigmoid shape of binding curve = that given the average binding affinity, at low levels the affinity will be lower than you expect, while at higher levels the affinity will be higher than you expect. It also means that middle range binding is very strongly substrate dependent. This is quite a useful trait for a carrier, although a less useful trait for a storage bank.
Regulation of oxygen affinity:
explain the cause of and the effect of rightward shift of the Hb dissociation curve
CO2 -> rightward shift (R)
H+ -> rightward shift
Cl- -> rightward shift
2,3-DPG -> R
Diphospho-glycerate
Bis-phospho-glycerate
Muscle activity encourages Hb to release O2
Cause
R (rightward shift) -> ↑ affinity for O2
Facts about 2,3-DPG
- Binds to Hb
- Lowers affinity of Hb for O2
- 2,3-DPG found in erythrocytes at 5 mM
- Tiny molecule compared with Hb
Effect of 2,3 DPG on the Hb dissociation curve
↑ 2,3-DPG —> ↓ affinity for O2
foetal Hb F has low affinity for 2,3-DPG
- versus maternal blood
- Thus Hb F has a higher binding affinity for oxygen than Hb A
Foetal vs Maternal Hb O2 saturation curves
Adult Haemoglobin curve (green) is S shaped.
This is b/c of cooperativity
Myoglobin curve (red) is exponential; not S shaped.
