L3- Haemoglobin and Myoglobin Flashcards Preview

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Flashcards in L3- Haemoglobin and Myoglobin Deck (37):

What is the physiological role of Haemoglobin?

Oxygen is not a polar molecule and therefore does not dissolve well in blood. Haemoglobin carries oxygen from the lungs to respiring tissues.


What is the physiological role of myoglobin?

Oxygen is not a polar molecules and therefore does not dissolve well in aqueous solutions. Myoglobin accepts oxygen from Haemoglobin and transports it to the tissues and muscles where it is mainly present.


Why is Haemoglobin more suitable for its role as an oxygen transporter?

Co-operative binding - more sensitive to smaller changes in oxygen concentration, therefore can pick up in lungs and drop off at tissues.
Cooperative binding allows it to carry twice the amount of oxygen (thanks to increases afinity) than it could without this cooperation.
Can carry 4 O2 vs Myoglobin's 1


How is myoglobin more suitable for its role as an oxygen carrier in tissues?

It has a higher afinity for oxygen than myoglobin and therefore can take oxygen off of Haemoglobin at the tissues.


How many oxygens can each haeme bind to in Haemoglobin and myoglobin?



What is the maximum amount of oxygen that Haemoglobin can carry?



How is haem bound to the protein part of Haemoglobin?

Via a covalently bound histidine residue


How does the oxygen dissociation curves of Haemoglobin and myoglobin differ?

Myoglobin' curve is hyperbolic - as the concentration of oxygen increases so does the percentage saturation of myoglobin until it levels off at 100%.
Haemoglobin's curve is sigmoidal and it has lower afinity than myoglobin (shifted further to the right). It is sigmoidal because its showing a the percentage saturation of a mixed population of Haemoglobin in its T-state or R-state at each ppO2, therefore is a mix of the low-affinity state curves and the high-affinity state curves.


Describe the structure of haemoglobin

Tetramer: 2 alpha and 2 beta chains in the adult form
Each chain contains a haeme prosthetic group
Conformation of each polypeptide chain is very similar to that of myoglobin


What effect does oxygen binding have on Haemoglobin's conformation?

Oxygen binding promotes a change in Hb from its T-state to its higher oxygen-afinity R-state. This promotes the binding of subsequent oxygen molecules = COOPERATIVE BINDING


Define cooperative binding of oxygen to haemoglobin

The binding of one oxygen molecule promotes the binding of oxygen to the next subunit.


What are the advantages to Haemoglobin's sigmoidal dissociation curve?

It means that Haemoglobin is more sensitive to small differences in O2 concentrations and therefore is more efficiently carried from the lungs to the tissues. Thanks to cooperative binding Haemoglobin can carry double the amount of oxygen.


What is the affect of 2,3-BPG on Haemoglobin?

It is a bi-product of glycolysis that acts like an allosteric inhibitor to Haemoglobin.

It lowers Haemoglobin's affinity for oxygen and therefore increases the amount of oxygen that is released at respiring tissues


How many 2,3-BPG bind per Hb tetramer? How does it bind?

One. It contains negatively charged phosphate groups which bind to positively charged Haemoglobin residues.


What affect does BPG have on the oxygen dissociation curve?

Shifts it to the right


What is the Bohr Effect?

The Bohr effect is the name given to the effect that pH and CO2 had on the binding and release of oxygen by Haemoglobin. It refers specifically to the release of oxygen from Haemoglobin when the pH falls (increase in the concentraion of H+) or the [CO2].
Metabolically active tissues produce large amounts of H+ and CO2 (both from H2CO3 ions), therefore the Bohr effect ensures that delivery of oxygen is coupled to demand.


What affect do H+ and CO2 have on the oxygen dissociation curve?

Both shift the curve to the right.


What is the affect of CO on oxygen transport?

CO combines with ferromyoglobin and ferrohaemoglobin and blocks oxygen transport.
It binds 250X more readily to Hb than oxygen.
It also increases the affinity for oxygen for unaffected subunits, so Hb can take up oxygen in the lungs but cannot release it at the tissues.
COHb> 50% is fatal
If all 4 subunits of Hb are blocked with CO the molecule is effectively dead.


How would you treat carbon monoxide poisoning?

Could use a hyperbaric chamber to increase the ppO2 in the lungs or in serious cases do a blood transfusion.


What are the subunits that make up normal adult HbA?

2x alpha subunits
2x beta subunits


What are the subunits that make up foetal Haemoglobin HbF?

2x alpha subunits
2x gamma subunits


What are the subunits that make up HbA2?

2x alpha subunits
2x delta subunits


Glycosylation of Hb produces which marker for long-term diabetes control?



What property of HbF is advantageous to the foetus?

HbF has a greater afinity for oxygen than HbA which allows transfer of oxygen to the foetal blood supply from the mother.


What amino acid substitution occurs to Haemoglobin causing sickle cell anaemia?

Glutamate to Valine ("glutval'!)


How does the amino acid substitution in Sickle Cell anaemia affect the Haemoglobin?

1. It changes a hydrophilic amino acid for a hydrophobic amino acid
2. HbS then cluster together to prevent this hydrophobic AA interacting with water.
3. These clumps tend to bind the the RBC membrane, making the membrane more rigid.
4. This means that the RBC is not as flexible and can get block microvasculature and is more prone to lyse.


What causes Thalassaemias?

Thalassaemias are a group of genetic disorders where there is an imbalance between the number of alpha- and beta- globin chains.


What happens in Beta-Thalassaemias?

There is a decreased or absent beta-globin chain production.
Alpha-chains are UNABLE to form stable tetramers and can precipitate out of solution.
Symptoms appear AFTER birth.


What happens in Alpha-Thalassaemias?

There is a decreased or absent alpha-globin chain production.
Beta-chains CAN form stable tetramers (HbH) with increased afinity for oxygen (don't release)
Onset BEFORE birth


Name three things that decrease Haemoglobin's afinity for oxygen



Why does BPG have a greater afinity for deoxygenated Hb than oxygenated?

It is due to spatial changes 2,3-BPG (with an estimated size of 9 angstroms) fits in the deoxygenated Haemoglobin configuration (11 angstroms), but not as well in the oxygenated (5 angstroms).


Why can acidosis precipitate a Sickle Cell crisis?

At high concentration of H+, the afinity of Haemoglobin for oxygen will be decreased (the Bohr effect), therefore more Haemoglobin will be in their deoxygenated T-state. In this state the mutant hydrophobic residue in Sickle Cell individuals is more exposed and Hb polymerises, causing sickling of cells. Therefore the more T-state Haemoglobin, the more Sickled cells, which can cause a sickle cell crisis.


The binding curve of Haemoglobin is sigmoidal because:

The binding of oxygen to one haem group increases the oxygen affinities of the other haem groups.


In Haemoglobin the transition form T state to R state (low to high afinity) is triggered by:

Oxygen binding


Why is the Bohr effect physiologically important?

It allows a link between oxygen demand of the tissues to be coupled with oxygen delivery by Haemoglobin. Metabolically active tissues produce CO2 and other acidic compounds (e.g. Lactate). This causes a localised lowering of the blood pH, causing a decrease in the affinity of Haemoglobin for oxygen. Hence, O2 is released at the sites of most need.


How can a deficiency of niacin in the diet cause a reduction in the activity of NAD and NADP dependent enzymes?

Niacin is needed in the body for the formation of Nicotinamide, a component of the coenzymes Nicotinamide adenine dinucleotide (NAD) and NADP. A deficiency in niacin affects all NAD(P) dependent dehydrogenases and can cause the disease pellagra.
Niacin (nicotinic acid) is a vitamin that is synthesised from the amino acid tryptophan. However humans cannot synthesise sufficient quantities of this to meet its requirements and most niacin must be derived from dietary sources.


How does a competitive inhibitor differ from a non-competitive inhibitor?

A competitive inhibitor affect the Km but not the Vmax
A non-competitive inhibitor affects the Vmax but not the Km.