Haemoglobin Structure & Synthesis Flashcards
What is Haemoglobin?
An iron containing protein synthesised by erythroblast precursors in bone marrow
What is Haemoglobin composed of?
2 dissimilar pairs of polypeptide chains which encloses an iron containing porphyrin ring called haem
What are the functions of the components of Haemoglobin?
Haem - O2 transport
Globin - Protects haem from oxidation, renders molecule soluble, variation in O2 affinity
What are the 3 stages of Haemoglobin synthesis?
Embryonic, foetal, & adult
What differs between different haemoglobin structures?
Globin chains
What 2 chromosomes are responsible for haemoglobin synthesis?
11 & 16
What are the types of Haemoglobin
~A
~A2
~F (Foetal)
~Gower 1
~Gower 2
~Portland 1
~Portland 2
Where in the early embryo is haemoglobin synthesised?
Yolk sac
What types of Haemoglobin are synthesised at week 5?
Gower 1, Gower 2, Portland 1, Portland 2
When are other forms of haemoglobin synthesised?
6 weeks
The formation of what Haemoglobin is essential for life?
Gower 2
During weeks 10-12 where is haemoglobin synthesised and what type is synthesised?
~Liver & spleen
~Foetal haemoglobin & haemoglobin A (later)
What takes over haemoglobin synthesis from the liver and spleen in later foetal development?
Bone marrow
What happens when bone marrow takes over haemoglobin synthesis?
Increased production of Haemoglobin A
Healthy levels (%) of haemoglobin A, A2 and F in adults?
A: ~97%
A2: 2.0-3.3%
F: 0.2-1.0%
How much iron should be in the body?
Male: 50 mg/kg
Female: 35 mg/kg
How much of the body’s iron is in haemoglobin?
65%
What is haemoglobin used for in RBC precursor cells?
Erythropoiesis
Where else is iron stored in the body?
~Ferritin and it’s insoluble form haemosiderin (macrophage of bone marrow, liver, spleen) ~30%
~Myoglobin in muscles
~Cytochrome enzymes in cells
Dietary sources
Red meat (especially liver), animal & fish products, leafy greens (poor source), legumes, fortified cereals & milks
What is the average amount of iron consumed in the Western diet
10-15mg - 5-10% absorbed
What percentage of dietary iron is absorbed during iron deficiency and pregnancy?
20-30%
What forms can dietary iron he found in?
Ferrous (Fe2+) & Ferric (Fe3+) states
What is the haem form of iron?
-Red meat & fish
-Ferrous state - quicker to absorb
-Released from the gut by haemoxygenase 1
What is the non-haem form of iron?
-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
What controls iron absorption?
Amount of iron in diet, availability and the form, the bodies stores and requirements
What causes iron to be lost?
Menstruation, GI bleeds, epithelial cells in skin, gut, urinary tract
What is the main source of iron in the body?
The breakdown of RBCs
What happens to old RBCs?
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
What can the amount of iron being carried by transferrin tell us?
General iron status
Where are transferrin receptors found?
On the lining of cells involved in erythropoiesis and iron storage
What is the function of transferrin receptors?
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
What stages of erythropoiesis does haemoglobin get synthesised at?
Erythroblast stage - 65%
Reticulocyte stage - 35%
Where is haem synthesised?
Mitochondria
Where is globin synthesises?
Ribosome
Haem structure
-Pigment - porphyrin class
-4 pyrrole rings linked by methene bridges each bound to central ferrous ion
Haem synthesis
-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
Globin synthesis
-chains of amino acids
-adults - 2 alpha (chromosome 16) & 2 beta (chromosome 11)
-different globin chains in embryo and foetus
Primary Structure of Globin
Amino acid chain - sequence & identities known
Secondary Structure of Globin
9 non-helical sections & 8 helical sections
Tertiary Structure of Globin
Folding of individual chains into 3D shapes
Quaternary Structure of Globin
4 subunits join together (globin & haem ring) - tetramer
Functions of haemoglobin
Transport 02 to tissues, transport CO2 to lungs
What are the 3 different forms of CO2 that exist in the body for removal?
Bicarbonate ions 78%
Haemoglobin 13%
Solution in plasma 9%
3 Stages of iron deficient anaemia
1 iron stores depleted
2 RBC synthesis altered
3 Isn’t enough iron to make haemoglobin
Markers of iron deficient anaemia
-Microcytic hypochromic RBCs
-Decrease in RBC, Hb, MCV, MCH, MCHC
-Decrease in ferritin
Symptoms of iron-deficient anaemia
-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
Treatment of iron deficient anaemia
-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
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