Haemoglobin and Haem Synthesis

Question 1

Where is most of the iron in the body taken from?

Answer 1

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)

Question 2

What is the amount of iron being carried by transferrin a good indicator of?

Answer 2

The general iron status.

Question 3

What are transferrin receptors and what is their role in the iron transport around the body?

Answer 3

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.

Question 4

What is the role of ferritin in the transport of iron in the body?

Answer 4

Ferritin is the storage form of iron.

Question 5

Where does haemoglobin synthesis begin?

Answer 5

In the proerythroblast, this is an early precursor of the red cell found in the bone marrow.

Question 6

What are the two stages that haemoglobin synthesis occurs at and that are their percentages?

Answer 6

Erythroblast (65%)

Reticulocyte (35%)

Question 7

Is haem and globin synthesis synthchronised?

Answer 7

Yes, they are well synchronised.

Question 8

What is the name of the class of pigments which haem belongs to?

Answer 8

Proyphyrin.

Question 9

What is the haem structure composed of generally?

Answer 9

4 pyrrole rings linked by methene bridges

Each bound to a central ferrous iron.

Question 10

Where is the most important site of haem synthesis?

Answer 10

In the developing red cell precursors, the erythroblasts.

Question 11

What are the two main enzymes involved in haem synthesis?

Answer 11

Succinyl Co enzyme A transferase
Aminolevulinate synthase (ALAS)
Also: Ferrochelatase

Question 12

What is another name for the haem synthase enzyme and what is its role?

Answer 12

Ferrochelatase

Catalyses the insertion of iron into the haem molecule in the mitochondria.

Question 13

What does the first step of haem synthesis involve. Combination of 2 molecules, product and catalyst name?
Location?

Answer 13

Glycine + Succinyl Co A
ẟ - Aminolevulinic Acid (ẟ -ALA)
Catalyst: ẟ - ALA synthase
Mitochondria

Question 14

What relies on ẟ - ALA synthesis? (from step 1 )

Answer 14

Several cofactors, vitamin B6, free ferrous and copper ions.

Question 15

What does the second step of haem synthesis consist of?
A product, under the influence of 2 enzymes.
Location?

Answer 15

2 ẟ - ALA combine to form Pyrrole (called Pophobiliogen (PBG))
Under influence of ẟ Dehydrogenase + Glutathione.
Occurs in cytoplasm.

Question 16

What does the third step in haem synthesis consist of?

Location?

Answer 16

Four PBG combine to form a tetrapyrrole (Uroporphyrinogen (UPG)
In cytoplasm.

Question 17

What does the fourth step in haem synthesis consist of? Conversion

Answer 17

Conversion to UPG to CPG

Question 18

What does the fifth step in haem synthesis consist of? Change of location, conversion

Answer 18

This is the movement of CPG from cytoplasm to mitochondria

Conversion of CPG to protoporphyrinogen IX to protoporphyrin IX.

Question 19

What is the final step in haem synthesis.

Insertion, catalyst

Answer 19

A central ferrous ion is inserted to complete the synthesis.
Ferrochelatase catalyzes the insertion of the haem molecule into the mitochondria.

Question 20

What does a hemoglobin consist of?

Answer 20

4 globin chains each containing a prosthetic haem group.

The synthesis of the haem and the globin moieties proceeds separately.

Question 21

Which chromosome controls the alpha globin chain sythnesis?

Answer 21

Chromosome 16

Question 22

Which chromosome controls the beta globin chain synthesis?

Answer 22

Chromosome 11

Question 23

What does the formation of haem increase?

Answer 23

Globin synthesis.

Lack of haem formation reduced globin synthesis.

Question 24

What are the four structures of haem?

Answer 24

Primary (aa sequence)
Secondary (globin chain types)
Tertiary (folding into 3D)
Quaternary ( 4 subunits - each with haem group)

Question 25

What are the different globin chain types in the secondary structure of hemoglobin synthesis?

Answer 25

9 non-helical sections

8 helical sections.

Question 26

What is the name of the haemoglobin molecule as it has four globin chains each with haem groups attached?

Answer 26

Tetramer.

Question 27

Describe the binding of O2 to H?

What does this do to the beta chains?

Answer 27

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.

Question 28

What happens to the H molecule structure when it is oxygenated?

Answer 28

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.

Question 29

What does the oxygen-hemoglobin dissociation curve plot?

Answer 29

% saturation of H against the partial pressure of O2 carrying the H at different PO2.

Question 30

The H oxygen dissociation curve is?

Answer 30

Sigmoidal.

Question 31

What is P50?

Answer 31

This is the pressure of O2 at which H is 50% saturated with O2, normally 26.6mmgHg (mercury)
4kPa pf pressure.

Question 32

What does the position of the curve depend on ?

Answer 32

2, 3 - DPG
H+ ion conc (pH)
CO2 in rbc.
Different types of H

Question 33

What do ventilators do?

Answer 33

They artificially increase the pressure of oxygen in the body needed to saturate H.
Different types of H will have different affinities for oxygen.

Question 34

What conditions can affect oxygen saturation?

Answer 34

High altitude (O2 tension low - difficult to saturate)
Types of H
Certain pathological conditions.

Question 35

What can cause a right shift in the oxygen dissociation curve?

Answer 35

High 2, 3 - DPG
High H+ (pH)
Increased temp
Reduced affinity

Question 36

What can cause a left shift in the oxygen dissociation curve?

Answer 36

Low 2, 3 - DPG
HF
Decreased pH / H+
CO
Decreased temp

Question 37

How is CO2 excreted via the lungs? (3 - forms)

Answer 37

Form of bicarbonate ions (HCO3-) - 78%
Bound to H and other blood proteins - 13%
In plasma solution - 9%

Question 38

What is responsible for the catabolism of red cells?

Answer 38

Enzymes

As the red cell ages, the enzymes that are responsible for producing the energy in the cell decrease in activitiy.

Question 39

Where are old rbc broken down?

Answer 39

Within the RE system in the spleen, bone marrow and liver.

Question 40

What happens to the iron released from the haemoglobin?

Answer 40

This iron can be reutilized to form new H in primitive red cells in the marrow.

Question 41

What are the two pathways for the catabolism of protoporphyrin (last step in haem synthesis before insertion of central ferrous ion)?

Answer 41

Can be expired by the air as CO2
Brought to liver, bilirubin is produced, conjugation of bilirubin glucuronicides - stercobilinogen - urobilinogen —— urine and faeces.