BioChemistry: Lecture 20
Oxygen Transport
Terms
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- Hemoglobin (HbA)
- major protein in blood responsible for oxygen transport.
- Myoglobin (Mb)
- This protein is found mostly in skeletal muscle. Consists of a single, carefully folded globin polypeptide. A single heme group is non-covalently associated with each globin chain
- Partial Pressure
- In a mixture of gases, each component makes a specific contribution, which is directly proportional to its concentration.
- Barometric Pressure
- atmospheric pressure or air pressure
- Iron-ferrous iron Fe2+
- The major fraction of oxygen in the blood which is complexed to this. This iron is present in the heme group of Hb
- 0.13 mmol/L
- Oxygen concentration in arterial blood
- 8.7 mmol/L
- In arterial blood, with a Hb concentration of 150g/L and oxygen saturation of 97.4%, the contribution of the protein bound oxygen is this amount
- ~200ml
- amount of dissolved oxygen per liter of blood
- Tetramer
- This is composed of 4 heteromers
- Non-covalent linkages
- Each of the 4 globins has a heme group bound to it be these type of linkages. Each are able to carry an oxygen atom
- HbA chains
- Alpha 1, alpha 2, beta 1, and beta 2
- Fe3+
- If the Fe2+ is oxidized through this, it will not be able to carry oxygen
- Porphyrin ring
- This structure has Fe2+ in the middle with four Nitrogen molecules bound-and in the z plane: histidine is bound in the 5th position & oxygen is bound in 6th position
- Alpha helices
- Most of the helices in HbA and Mb are this type
- 6
- iron prefers this many ligands
- Phenylalanin
- This makes hydrophobic and electrostatic interactions with the porphyrin rings
- Proximal and distal histidines
- In the oxygenated globin structure, the heme is positioned between these, which are also referred to as Histadine F8 and Histadine E7.
- Imadazole nitrogen
- ONly the Histadine F8 has this which is close enough to bond with iron
- Heme
- Gives blood and muscle their characteristic purple-red color
- Deoxygenated
- In this type of globin, the 6th position remains vacant.
- Polar
- These type of amino acids are located on the exterior surface of globin polypeptides-making them highly soluble
- p50
- The value of partial pressure of oxygen at which half of the ligand sites are occupied by oxygen
- 4mmHg
- Mg has a this p50, which represents a high affinity for oxygen
- Structural changes
- When deoxygenated Hb becomes oxygenated, this takes place
- Co-operativeity
- The binding of oxygen to one heme in HbA that will alter the ability of the other heme groups to bind to oxygen. so this is where the globins cooperate to maximize oxygen binding
- Fractional oxygen saturation
- The greater the fraction, the greater the saturation
- Hill coefficient
- Describes cooperativity in the molecule. Ex: if there is no cooperativity in HbA molecule, then n=1, but if n=2.7 it implies cooperativity between subunits
- 27mmHg
- HbA's p50; affinity for oxygen is much lower than compared to 4mmHg of Mb
- Associates or dissociates
- Big structural changes occur when oxygen undergoes this
- Tense and relaxed states
- Structural changes involving a shift between these two conformational states
- Relaxed state (R)
- This state can bind oxygen. It is oxygenated
- Tense state (T)
- It is deoxygenated. Oxygen affinity is lower for the Tense state
- Allosteric
- Binding to the site other than the active site to modify the protein
- 2,3 BPG
- this is an offshoot of glycolosis pathway that reduces affinity of Hb for oxygen. this binds preferably to deoxygenated Hb. A fully saturated Hb is unable to bind to this.
- Homotropic modulator
- If oxygen can influence its own binding
- Heterotropic modulators
- If oxygen can influence it's own binding, then the others (hydrogen ions, CO2, and 2,3 BPG) will be called this
- Bohr effect
- If blood pH decreases, affinity of O2 for Hb will also decrease. [CO2 + H2O -> H2CO3 by CA -> HCO3 + H+ -> ?]
- Highly metabolic tissues (eg-muscle, which is more acidic)
- As blood moves here, the Hb affinity for Oxygen decreases, thus releasing the bound oxygen to these tissues
- Exercising muscles
- This generates more heat which increases temperature
- Increasing temperature
- This decreases the affinity of Hb for oxygen. Thus, Hb readily releases the oxygen.
- To the right
- 2,3 BPG shfits the oxygen dissociation curve this way, which means we need a higher partial pressure of Hb to be saturated. In other words, the presence of 2,3 BPG allows the oxygen to dissociate easily.
- Lack of 2,3 BPG
- Without this, the oxygen saturation curve of HbA would be the same for Mb
- Carbamino Adducts
- CO2 reacts reversibly with unprotonated N-terminal amino groups of the globin chains to form this
- pCO2
- Oxygen dissociation curve will shift to the right as this increases
- Erthyrocyte carbonic annhydrase
- Most of the tissue CO2 is hydrated in the presence of this
- Carbonic acid
- Co2 can form this. it reacts with the N-terminal group to form carbamino adducts
- Nitric Oxide
- Gaseous, free radical that can oxidize biological macromolecules. It is synthesized in endothelial cells and in the brain. It is a vasodilator
- Neuroglobin (Ngb)
- Is expressed in the CNS and some endocrine tissues
- Cytoglobin
- expressed mainly in cell of fibroblast origin
- Methemoglobinemia
- This can be acquired or inherited. It is formed when the ferrous iron (Fe2+) is oxidized to ferric iron (Fe3+)
- Tyrosine
- In mutations, distal histadine is replaced by this, making iron more susceptible to oxidation.
- NADH cytochrome b5 reductase
- can reduce most of the Met-Hb back to normal Hb