BY /

AMR
ASHR

BIOCHEMICTRY
RESPIRATORY SYSTEM
LECTURE 2

BY / AMR ASHRAF AWAD

BY / AMR ASHRAF AWAD
[BIOCHEMICTRY] BY / AMR ASHRAF AWAD

HB structure and binding

HB chemical structure
• Haemoglobin is a conjugated protein, containing haemas prosthetic groupand
globin as the protein part.
• The polypeptide chains of globin of adult Hb, are characterised by a relatively
high content of histidine (His) and lysine (Lys).

Haem Globin
It is a Fe-porphyrin compound. The protein part of
✓ The porphyrins are complex compounds with a Hb. It is composed
tetrapyrrolestructure, each pyrrole ring having the following of four
structure: polypeptide
✓ Four such pyrroles called I to IV, are combined through – chains.
CH= bridges, called as methylene bridges to form a ✓ Each
porphyrin nucleus. polypeptide chain
✓ Ferrous iron (Fe++) occupy the centre of the compound contains a ‘haem’,
ring structure and establish linkages with all the four in the socalled
nitrogens of all the pyrrole rings. haem-pocket. Thus
✓ The Fe, besides its linkages to four nitrogens of the one Hb molecule
pyrrole rings, is also linked internally (5th linkage) to the contains four
nitrogen of the imidazole ring of histidine (His) of the haem units.
polypeptide chains.

Different HB types
• Most normal human Hb contains two αchains + 2 other chains (which may be
β,Y ,E or ) depending on the type.

1. Hb-A1: (α2β2) 2. Hb-F 3. Hb-

Normal adult Hb • Human foetalHb is designated as • A minor
consists of two α Hb-F and it is α2Y2. component of
and two β chains. 90 • Has higher affinity than HBA1 normal adult Hb
to 95 per cent of Hb (↓ o2 delivery to tissues).
of normal adult is of • Present infoetal life & disappears
(2.5%).
this type. after one year.
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4. Hb-A1C 5. Methaemoglobin 6. HB S
(Glycosylated Hb) (chocolate colored)
• A minor • It is a derivative in which • Due to mutation in β-
glycosylated form Fe is in the ferric state globin gene.
is also found in • it is a true oxidation • Causes sickle cell disease.
adult RBCs. • Normal RBCs are quite
• Normally, it is
product of Hb. elastic, which allows the
present in conc.of • Increased amount of cells to deform to pass
3 - 5 % of total Hb. methaemoglobin in blood through capillaries.
However, in above normal is called as • In sickle cell disease, low
patients with D.M. “methaemoglobinaemia”. O2 tension promotes RBCs
it may be • Can’t bind O2. sickling → damage the cell
increased to as membrane and decrease the
much as 6 -15 % of cell's elasticity → these rigid
total Hb. blood cells are unable to
deform as they pass through
narrow capillaries →vessel
occlusion and ischemia.
• RBCs becomes liable for
hemolysis.
Mechanism of HB binding to oxygen
1-Hb can readily combine with O2. 3- Each haem can bind only one mol.
The combination is loose and of O2. Since each molecule of Hb
reversible. The gas is taken up readily contains 4 mols. ofhaem; hence
at high partial pressures (e.g. in the
lungs) and is released as readily at
one mol. of Hb can maximally
low O2 pressures (e.g. in tissues), combine with four mols of O2.
thus providing an effective system
for transport of O2 from the
atmosphere to the cells of the body.
2- Fe remains in the ferrous 4-Cooperative binding of oxygen by the four
subunits of hemoglobin means that the binding
state both in deoxygenated Hb of an oxygen molecule at one heme group→
and oxy-Hb. increases the oxygen affinity of the remaining
heme groups in the same hemoglobin tetramer

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(Haem-haem Interactions).
Two states of Hb
‘R’ state ‘T’ state
-This is a relaxed state and it is -This is a tense/taut state and it is
oxygenated Hb. deoxygenated Hb.
This form is interconvertible This form is interconvertible

Correlation of structure of different types of HB to oxygen binding

capacity
Carboxy-Hb Met HB
• Oxidation of the
Combination with CO Combination with heme iron in
CO2 hemoglobin to the
-CO combines with haem portion of Hb to • Hb combines with ferric (Fe3+) state
form carbon monoxide Hb (carboxy-Hb or CO2 to form forms
carbonyl Hb). methemoglobin,
carbaminohaemogl
✓ It is a much firmer combination, as
obin. In this case, which cannot
compared to oxy-Hb and not reversible.
✓ Affinity of Hb to CO is 210 times more the combination is bind O2. This
than O2. with the globin oxidation may be
✓ Lethal action is due to inhibition of rather than with the caused by the
cytochrome oxidase of electron transport haem. CO2 action of certain
chain and thus stops cellular respiration. combines with NH2 drugs, such as
✓ Poisoning by CO is a common danger of group. nitrates, or
modern life. Carbon monoxide is
endogenous
particularly dangerous as It is
colourlessand odourless. products.

Case
A 67-year-old man presented to the emergency department with a 1-week
history of angina and shortness of breath. He complained that his face and
extremities had a “blue color.” His medical history included chronic stable angina
treated with dinitrate and nitroglycerin. Blood obtained for analysis was chocolate
colored

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