2. Introduction
• Hemoglobin is a protein ( Heme protein )
• Types of proteins are
globular proteins ( functional proteins )
linear proteins ( structural proteins )
• Hb is considered of globular proteins.
• Mature RBCs do NOT synthesis Hb, while
immature RBCs synthesis Hb.
• Mitochondria is very important for Heme
synthesis
3. Hemoglobin = Heme + globin ( protein )
Note : globin is considered as a protein so
that it synthesized by RER.
4. Heme synthesis
• Heme = Protoporphyrin + Iron
• Protoporphyrin = Iron free Heme
• Protoporphyrin consist of 4 pyrrol rings.
• Iron have 6 coordination, 4 bind with these 4
pyrrol rings of protoporphyrin, 1 bind with
histidine ( anino acid ) from globulin and 1 is
free (bind to Oxygen , CO2 respectively)
6. Each hemoglobin molecule ( Globular protein ) consists of
1. 4 Heme
2. 4 linear proteins each one bind to a Heme
7. 1) Heme synthesis start with 2 simple molecules
a. Glycine ( amino acid )
b. Succinyl Co-A (intermediate of citric acid cycle)
2) Reaction of these 2 simple molecule together
with a Co-Factor ( Vitamin B6 ) will produce
aminolevulinic acid synthase ( ALA Synthase )
• This step also called ( regulatory step ) or ( rapid
limited step )
• Regulatory step : When this step being enhanced
, all other pathways will be enhaced ( fast ) and if
this step have inhibitory action, all other pathways
will be inhibited.
8. 3. Then some steps will happened in the
cytoplasm. ( NOT important )
4. Then this molecule will return to
mitochondria, when a protoporphyrin
formed.
5. Protoporphyrin will bind to Iron (ferrous)
6. At same time, globulin is being
synthesized in RER.
7. Protoporphyrin + ferrous + globulin will
form Hemoglobin.
9.
10. Iron in Hemoglobin is ferrous or
ferric ? Why ?
• Iron in ferrous form ( 6 coordination )
1) 4 bind with protoporphyrin
2) 1 bind to histidine ( globin )
3) 1 free bind to O2 or CO2 respectively
• Where in ferric form we well have one bond
missing ( malfunctional hemoglobin )
• Heme and globulin are not isolated, the bind
together by Iron,
11. Notes
• When O2 bind to Iron this process is called “
oxygenation “ not “ oxydation “ and oxygen transport
through circulation as a mloecular form ( O2 ).
• The oxidation stage of the iron does NOT change.
Oxidation of Fe2+ to Fe3+ only occurs occasionally.
The oxidized form, methemoglobin, is then no longer
able to bind O2. The proportion of Met-Hb is kept low
by reduction (see p. 284) and usually amounts to only
1–2%.
12. Types of Hemoglobin
Normal
• Different types of Hb due to different type
of globin NOT Heme.
and small amount of
• Adult have HbA
HbA2.
• Fetus Have HbF.
13. Types of Hemoglobin
Type Formula
HbA α2β2
HbA2 α2δ2
HbF α2γ2
HbF have more affinity to oxygen than HbA.
14. Gas Transportation
• Why we use hemoglobin as a transporter for
oxygen ?
1. Because of low solubility of oxygen in
water.
2. Hemoglobin have a regulatory effect on
oxygen concentration in lungs and tissues.
Note : all tissue required of oxygen and 20% of
CO2 from metabolic wastes transport via Hb.
15. Allosteric effect
• When an enzyme reacts to effectors with
conformational changes that increase or
reduce its activity, it is said to show
allosteric behavior
• Many substances act on Hb as an allosteric
substances.
• Although Hb is NOT an enzyme, but it have
all the characteristics of enzymes
16. • Substances that have an allosteric effect on
Hb are :
1. 2,3 DGP (intermediate factor in glycolysis)
2. H+ ( i.e. ph affect on Hb )
3. CO2
17.
18. Forms of Hb
• When Hb have high affinity to oxygen in
lung is called ( oxyhemoglobin ) and
refereed to as R form ( R from Relax )
19. • When Hb have low affinity to oxygen in
tissue is called ( deoxyhemoglobin ) and
refereed to as T form ( T from Tense )
20. • Allosteric substances act as a stabilizer for
T form of Hb.
• in other worsds, affecting on the saturation
of Hb with oxygen.
21. • Myoglobin saturation curve do not show
allosteric effect because of have NO affinity
to 2,3 DGP.
• Hb saturation curve is sigmoidal ( S shape,
means saturation changes ) due to allosteric
effect.
22. Steps for O2- CO2 Transport
1. In lungs, Pressure of oxygen is high so it
diffuse from outside the body to inside the
body and bind with Hb. ( bond of one O2
to hemoglobin fascilate the binding of
other O2 moleculse )
2. In tissues, hemoglobin bind to 2,3 DPG
and that cause to decrease affinity of Hb to
Oxygen and releasing Oxygen to the
tissues.
23. 3. In the same time, CO2 is being bind to Hb
due to high pressure of CO2 inside tissues
and that reducing Hb affinity to Oxygen
( allosteric effect )
24. Affect of allosteric effectors
1. 2,3 DGP or ( BGP )
enters between two chains of β and
convert Hb from R to T form, reducing
affinity of Hb to oxygen and cause it to
release, also it referred to as
( shift to the right )
*Note : HbF have no affinity to 2,3DGP, So
the affinity of HbF to oxygen is more than
HbA that have affinity to 2,3DGP.
25. 2. H+ or pH and CO2
form from metabolic reactions in tissue,
bind to Hb and decrease the affinity of Hb
to Oxygent ( allosteric effect ) ans
specificly called ( Bohr effect ) .
