Haemoglobin Structure & Synthesis

Question 1

What is Haemoglobin?

Answer 1

An iron containing protein synthesised by erythroblast precursors in bone marrow

Question 2

What is Haemoglobin composed of?

Answer 2

2 dissimilar pairs of polypeptide chains which encloses an iron containing porphyrin ring called haem

Question 3

What are the functions of the components of Haemoglobin?

Answer 3

Haem - O2 transport
Globin - Protects haem from oxidation, renders molecule soluble, variation in O2 affinity

Question 4

What are the 3 stages of Haemoglobin synthesis?

Answer 4

Embryonic, foetal, & adult

Question 5

What differs between different haemoglobin structures?

Answer 5

Globin chains

Question 6

What 2 chromosomes are responsible for haemoglobin synthesis?

Answer 6

11 & 16

Question 7

What are the types of Haemoglobin

Answer 7

~A
~A2
~F (Foetal)
~Gower 1
~Gower 2
~Portland 1
~Portland 2

Question 8

Where in the early embryo is haemoglobin synthesised?

Answer 8

Yolk sac

Question 9

What types of Haemoglobin are synthesised at week 5?

Answer 9

Gower 1, Gower 2, Portland 1, Portland 2

Question 10

When are other forms of haemoglobin synthesised?

Answer 10

6 weeks

Question 11

The formation of what Haemoglobin is essential for life?

Answer 11

Gower 2

Question 12

During weeks 10-12 where is haemoglobin synthesised and what type is synthesised?

Answer 12

~Liver & spleen
~Foetal haemoglobin & haemoglobin A (later)

Question 13

What takes over haemoglobin synthesis from the liver and spleen in later foetal development?

Answer 13

Bone marrow

Question 14

What happens when bone marrow takes over haemoglobin synthesis?

Answer 14

Increased production of Haemoglobin A

Question 15

Healthy levels (%) of haemoglobin A, A2 and F in adults?

Answer 15

A: ~97%
A2: 2.0-3.3%
F: 0.2-1.0%

Question 16

How much iron should be in the body?

Answer 16

Male: 50 mg/kg
Female: 35 mg/kg

Question 17

How much of the body’s iron is in haemoglobin?

Answer 17

65%

Question 18

What is haemoglobin used for in RBC precursor cells?

Answer 18

Erythropoiesis

Question 19

Where else is iron stored in the body?

Answer 19

~Ferritin and it’s insoluble form haemosiderin (macrophage of bone marrow, liver, spleen) ~30%
~Myoglobin in muscles
~Cytochrome enzymes in cells

Question 20

Dietary sources

Answer 20

Red meat (especially liver), animal & fish products, leafy greens (poor source), legumes, fortified cereals & milks

Question 21

What is the average amount of iron consumed in the Western diet

Answer 21

10-15mg - 5-10% absorbed

Question 22

What percentage of dietary iron is absorbed during iron deficiency and pregnancy?

Answer 22

20-30%

Question 23

What forms can dietary iron he found in?

Answer 23

Ferrous (Fe2+) & Ferric (Fe3+) states

Question 24

What is the haem form of iron?

Answer 24

-Red meat & fish
-Ferrous state - quicker to absorb
-Released from the gut by haemoxygenase 1

Question 25

What is the non-haem form of iron?

Answer 25

-Vegetables & cereals -Ferric state - slow to absorb -Enzymes & acids release iron from protein complexes in food -Ferroreductase convert ferric ions to ferrous ions to be easily absorbed -Same process as Haem iron digestion after

Question 26

What controls iron absorption?

Answer 26

Amount of iron in diet, availability and the form, the bodies stores and requirements

Question 27

What causes iron to be lost?

Answer 27

Menstruation, GI bleeds, epithelial cells in skin, gut, urinary tract

Question 28

What is the main source of iron in the body?

Answer 28

The breakdown of RBCs

Question 29

What happens to old RBCs?

Answer 29

Broken down by macrophages of RE system - iron is released into the plasma - provides iron for transport protein transferrin - carries to be used to make new RBC

Question 30

What can the amount of iron being carried by transferrin tell us?

Answer 30

General iron status

Question 31

Where are transferrin receptors found?

Answer 31

On the lining of cells involved in erythropoiesis and iron storage

Question 32

What is the function of transferrin receptors?

Answer 32

Bind to transferrin - facilitates release of iron into cell -Increased during iron deficiency (low ferritin) to bind to more transferrin -Some are shed into plasma and can be measured

Question 33

What stages of erythropoiesis does haemoglobin get synthesised at?

Answer 33

Erythroblast stage - 65% Reticulocyte stage - 35%

Question 34

Where is haem synthesised?

Answer 34

Mitochondria

Question 35

Where is globin synthesises?

Answer 35

Ribosome

Question 36

Haem structure

Answer 36

-Pigment - porphyrin class -4 pyrrole rings linked by methene bridges each bound to central ferrous ion

Question 37

Haem synthesis

Answer 37

-Synthesised in most cells - most importantly in erythroblasts -Enzymes involved are Succincyl Co Enzyme A transferase, aminolaevulininic acid synthase (ALAS) -Haem synthase/Ferrocheletase - catalyses insertion of iron into haem in the mitochondria -Sychronised with globin synthesises - haem synthesis increases = globin synthesises increases -Needs entry of iron into the cell to occur

Question 38

Globin synthesis

Answer 38

-chains of amino acids -adults - 2 alpha (chromosome 16) & 2 beta (chromosome 11) -different globin chains in embryo and foetus

Question 39

Primary Structure of Globin

Answer 39

Amino acid chain - sequence & identities known

Question 40

Secondary Structure of Globin

Answer 40

9 non-helical sections & 8 helical sections

Question 41

Tertiary Structure of Globin

Answer 41

Folding of individual chains into 3D shapes

Question 42

Quaternary Structure of Globin

Answer 42

4 subunits join together (globin & haem ring) - tetramer

Question 43

Functions of haemoglobin

Answer 43

Transport 02 to tissues, transport CO2 to lungs

Question 44

What are the 3 different forms of CO2 that exist in the body for removal?

Answer 44

Bicarbonate ions 78% Haemoglobin 13% Solution in plasma 9%

Question 45

3 Stages of iron deficient anaemia

Answer 45

1 iron stores depleted 2 RBC synthesis altered 3 Isn't enough iron to make haemoglobin

Question 46

Markers of iron deficient anaemia

Answer 46

-Microcytic hypochromic RBCs -Decrease in RBC, Hb, MCV, MCH, MCHC -Decrease in ferritin

Question 47

Symptoms of iron-deficient anaemia

Answer 47

-Pale or yellow scaly skin -Fatigue -Shortness of breath & chest pain after exercise -hearaches, dizziness, light headedness -Cold hands & feet -inflammation of tongue -Brittle nails

Question 48

Treatment of iron deficient anaemia

Answer 48

-Oral administration of iron (II) salt or iron (III) - 100-200mg/ day for 3 months - increase of 0.2-0.3 g/dl/day -Parenteral iron treatment (iron saccharate complex or ferric carboxymaltose

Question 49

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