Haemoglobin and Haem Synthesis Flashcards
Where is most of the iron in the body taken from?
The recycled rbc, these are taken up by transferrin molecules and moved around the body to where they need to be.
Only a small proportion of plasma comes from dietary iron (absorbed through d and j)
What is the amount of iron being carried by transferrin a good indicator of?
The general iron status.
What are transferrin receptors and what is their role in the iron transport around the body?
Receptors on the lining od cells.
These receptors bind to transferrin and play a major role in the release of iron into the cell.
Increase in expression of surface transferrin - inadequate iron (occurs when iron deficiency (ferritin) is present.
What is the role of ferritin in the transport of iron in the body?
Ferritin is the storage form of iron.
Where does haemoglobin synthesis begin?
In the proerythroblast, this is an early precursor of the red cell found in the bone marrow.
What are the two stages that haemoglobin synthesis occurs at and that are their percentages?
Erythroblast (65%)
Reticulocyte (35%)
Is haem and globin synthesis synthchronised?
Yes, they are well synchronised.
What is the name of the class of pigments which haem belongs to?
Proyphyrin.
What is the haem structure composed of generally?
4 pyrrole rings linked by methene bridges
Each bound to a central ferrous iron.
Where is the most important site of haem synthesis?
In the developing red cell precursors, the erythroblasts.
What are the two main enzymes involved in haem synthesis?
Succinyl Co enzyme A transferase
Aminolevulinate synthase (ALAS)
Also: Ferrochelatase
What is another name for the haem synthase enzyme and what is its role?
Ferrochelatase
Catalyses the insertion of iron into the haem molecule in the mitochondria.
What does the first step of haem synthesis involve. Combination of 2 molecules, product and catalyst name?
Location?
Glycine + Succinyl Co A
ẟ - Aminolevulinic Acid (ẟ -ALA)
Catalyst: ẟ - ALA synthase
Mitochondria
What relies on ẟ - ALA synthesis? (from step 1 )
Several cofactors, vitamin B6, free ferrous and copper ions.
What does the second step of haem synthesis consist of?
A product, under the influence of 2 enzymes.
Location?
2 ẟ - ALA combine to form Pyrrole (called Pophobiliogen (PBG))
Under influence of ẟ Dehydrogenase + Glutathione.
Occurs in cytoplasm.
What does the third step in haem synthesis consist of?
Location?
Four PBG combine to form a tetrapyrrole (Uroporphyrinogen (UPG)
In cytoplasm.
What does the fourth step in haem synthesis consist of? Conversion
Conversion to UPG to CPG
What does the fifth step in haem synthesis consist of? Change of location, conversion
This is the movement of CPG from cytoplasm to mitochondria
Conversion of CPG to protoporphyrinogen IX to protoporphyrin IX.
What is the final step in haem synthesis.
Insertion, catalyst
A central ferrous ion is inserted to complete the synthesis.
Ferrochelatase catalyzes the insertion of the haem molecule into the mitochondria.
What does a hemoglobin consist of?
4 globin chains each containing a prosthetic haem group.
The synthesis of the haem and the globin moieties proceeds separately.
Which chromosome controls the alpha globin chain sythnesis?
Chromosome 16
Which chromosome controls the beta globin chain synthesis?
Chromosome 11
What does the formation of haem increase?
Globin synthesis.
Lack of haem formation reduced globin synthesis.
What are the four structures of haem?
Primary (aa sequence)
Secondary (globin chain types)
Tertiary (folding into 3D)
Quaternary ( 4 subunits - each with haem group)
What are the different globin chain types in the secondary structure of hemoglobin synthesis?
9 non-helical sections
8 helical sections.
What is the name of the haemoglobin molecule as it has four globin chains each with haem groups attached?
Tetramer.
Describe the binding of O2 to H?
What does this do to the beta chains?
Each H can bind 4 O2 molecules - less than 0.01 sec needed for oxygenation.
Beta chains move closer to each other when H is oxygenated.
What happens to the H molecule structure when it is oxygenated?
Beta chains move closer pushing the 2, 3 - DPG out of the H.
When the O2 is being unloaded, the Beta chains are pulled apart permitting the entry of the 2, 3 - DPG . This results in a lower affinity of O2.
What does the oxygen-hemoglobin dissociation curve plot?
% saturation of H against the partial pressure of O2 carrying the H at different PO2.
The H oxygen dissociation curve is?
Sigmoidal.
What is P50?
This is the pressure of O2 at which H is 50% saturated with O2, normally 26.6mmgHg (mercury)
4kPa pf pressure.
What does the position of the curve depend on ?
2, 3 - DPG
H+ ion conc (pH)
CO2 in rbc.
Different types of H
What do ventilators do?
They artificially increase the pressure of oxygen in the body needed to saturate H.
Different types of H will have different affinities for oxygen.
What conditions can affect oxygen saturation?
High altitude (O2 tension low - difficult to saturate)
Types of H
Certain pathological conditions.
What can cause a right shift in the oxygen dissociation curve?
High 2, 3 - DPG
High H+ (pH)
Increased temp
Reduced affinity
What can cause a left shift in the oxygen dissociation curve?
Low 2, 3 - DPG HF Decreased pH / H+ CO Decreased temp
How is CO2 excreted via the lungs? (3 - forms)
Form of bicarbonate ions (HCO3-) - 78%
Bound to H and other blood proteins - 13%
In plasma solution - 9%
What is responsible for the catabolism of red cells?
Enzymes
As the red cell ages, the enzymes that are responsible for producing the energy in the cell decrease in activitiy.
Where are old rbc broken down?
Within the RE system in the spleen, bone marrow and liver.
What happens to the iron released from the haemoglobin?
This iron can be reutilized to form new H in primitive red cells in the marrow.
What are the two pathways for the catabolism of protoporphyrin (last step in haem synthesis before insertion of central ferrous ion)?
Can be expired by the air as CO2
Brought to liver, bilirubin is produced, conjugation of bilirubin glucuronicides - stercobilinogen - urobilinogen —— urine and faeces.
