OXYGEN CARRYING

PROTEINS
 MYOGLOBIN
• Oxygen carrying protein in muscle
• Myoglobin is found in muscle cells which binds oxygen
efficiently and stores oxygen until muscle tissue needs it
• Skeletal muscles and heart muscles have high demand for
oxygen
• Myoglobin is important muscle protein that contains stored
oxygen
• Myoglobin has higher affinity to oxygen compared to oxygen
 MYOGLOBIN…
• Myoglobin is a monomeric protein or single
polypeptide chain of amino acids with tertiary
structure
• It contains heme proteins but unlike
hemoglobin it contains single polypeptide
chain
• Myoglobin has only one binding site for oxygen
 MYOGLOBIN…
• Myoglobin serve as an intracellular
storage site of oxygen in muscle tissues
• Myoglobin binds to single oxygen
molecule, stores oxygen in muscle tissues
HEMOGLOBIN
 HEMOGLOBIN
• Hemoglobin is oxygen carrying protein in
the blood specifically in red blood cells of
humans and animals.
• Globular protein that binds to oxygen
molecules and transports them from lungs
to other organs throughout the body.
• Cells in human body needs oxygen to produce
energy and oxygen is transported to the cell by
hemoglobin
• Hemoglobin also carries CO2 from cells to the
lung to be expelled
• Has lower affinity for oxygen compared to
myoglobin
• Hemoglobin is a tetramer with quaternary
structure containing four polypeptide chain
which are two alpha and two beta units
• Each polypeptide chain consists of amino acids
and heme group
• Heme contain poryphyrin which attaches iron
• Oxygen binds to iron and transported to
different parts of the body
 HEMOGLOBIN
• Hemoglobin is a complex protein found in
erythrocytes that contains an iron molecule
• Hemoglobin contain heme as prosthetic group
• The adult the polypeptide chain of globin is
characterized by high content of histidine and
lysine and small amount of isoleucine
 HEMOGLOBIN…
• In hemoglobin iron is linked to nitrogen of four
pyrole rings, nitrogen of histidine molecule of
globin and O2
• The pyrroles rings of Heam are connected to
each other by –CH bridges called methylene or
methyledine bridges to form poryphrin nucleus
 HEMOGLOBIN…
• The outer carbons of the four pyrrole rings
are which are not linked to methylene bridges
are numbered 1to8
• The Hydrogen at positions 1 to 8 are
substituted by different groups such as methyl,
vinyl, propionic acid.. in different compounds
• COOH group of 6 and 7 position of propionic
acid of Heam is linked with Arginine and Lysine
of polypeptide chain
• Hemoglobin contain four Polypeptide chains
and four Heam units
• Hydrophobic amino acids are found in the
interior of Hemoglobin molecule and
hydrophilic amino acids on their surfaces
 HEMOGLOBIN TYPES
1. Hb-A₁: Contains two α and two β polypeptide chains
with 141 and 146 amino acids respectively
• 90-95% of adult hemoglobin
2. Hb-F: found in Human fetal hemoglobin
• Contains α and γ chains
• Disappears at the end of year 1.
• If it persists after year 1 it shows some pathology
 HEMOGLOBIN TYPES…
3. Hb-A₂: 2.5% of adult Hemoglobin
• Contains two ẟ and two α polypeptide chains
4. Embryonic Hb: it is hemoglobin found in
first trimester (1 3months) of intra uterine
st

life.
• Contains two ε and two α polypeptide chains
• Occur in human erythrocytes
 HEMOGLOBIN TYPES…
• During the first three months of intrauterine life
there is rapid production of α and ε chains
• After three months of intrauterine life the α chain
persists and ε chain starts to disappear and new
polypeptide γ chain starts to develop
• After that during later stage of fetal life and after
birth the γ chain starts to decrease and β
polypeptide chain starts to increase
 HEMOGLOBIN TYPES…
5. Hb-A₃: an altered form of Hb-A₁ found chiefly
in old red cells.
6. Hb-A₁с (Glycosylated Hb): 3 to 5% of total
Hemoglobin
• In person with DM it can be 6 to 15%
• The major Hb in adult in addition to Hb-A₁
 RELAXED (R) AND TENSE (T) FORM
HEMOGLOBIN
• Oxygenated hemoglobin exists in relaxed (R)
state and in this state and O2 can enter to β
sub unit because valine residue in heam
pocket of β sub unit is removed.
• Relaxed (R) form hemoglobin Has high
affinity for O2
 RELAXED (R) AND TENSE (T) FORM
HEMOGLOBIN…
• Deoxygenated hemoglobin exists in tense or
taut (T ) state and O2 cannot enter into β
sub unit because heam pocket of β sub unit
is occupied by Valine
• Tense (T) form hemoglobin has low affinity
for O2
 HEMOGLOBIN
• Oxygen carrying pigment of RBC and Iron is essential
component of RBC

• The most widely used test of iron deficiency anemia but

results in miss classification of those with iron deficiency
as normal because, decline in hemoglobin occurs at the
last stage iron depletion stages

• There is a fall of hemoglobin during pregnancy due to

expansion of plasma volumes
 HEMOGLOBIN
• There is a fall of hemoglobin during pregnancy due to
expansion of plasma volumes

• In higher altitude due to the lower partial pressure of

oxygen and the reduced oxygen saturation of blood
there is the body generates adaptive mechanisms which
result in increasing concentration of hemoglobin and
hematocrit to compensate for reduced oxygen
saturation and the lower partial pressure of oxygen
 HEMOGLOBIN
• Deficiencies of other micronutrients such as folate,
vit-B12, vit-A, ribflavin, vit-B6, vit-C and copper are
associated with anemia
• Parasite infections lowers hemoglobin level by
rupturing RBCs
• Helminthes such as hookworms and flukes such as
shistosomiasis causes lower hemoglobin levels by
causing blood loss
 HEMOGLOBIN
• Chronic illnesses lowers hemoglobin levels
• Polycythemia and dehydration increases
hemoglobin levels
• Cigarette smoking is associated with elevated
levels of hemoglobin due to its effect on
reduction of oxygen carrying capacity of blood
caused by elevated carboxyhemoglobin level
HEMOGLOBIN METABOLISM
 HEME SYNTHESIS
• HEME is prosthetic group of compounds such as
hemoglobin, cytochrome, myoglobin and
catalase, peroxidase and tryphtophan pyrollase
• It is cyclic tetra pyrrole (protoporphyrin) with
ferrous iron at the center
 HEME SYNTHESIS
• Ferrous ion forms six bonds, 4 with pyrrole
rings, the other with histidine on globin
molecule and with O2.

• HEME is synthesized in liver and bone

marrow
 N
H
py rro l e

pyrrole rings
heme
 HEME SYNTHESIS STEPS
1. Condensation of succinyl COA with glycine in
mitochondoria forms aminolevulinic acid (ALA)
catalyzed by ALA synthase which contains
pyridoxal phospate CO-ENZYME
 Rate controlling step in HEME biosynthesis
 ALA SYNTHASE is regulated by the level of
HEME in the cell
 Step 1
In mitochondrion
COOH
COOH
H C
HSCoA + CO2 2

H 2C
CH 2
NH 2
CH 2

CH 2 + ALA synthase
（pyridoxal phosphate） C O

COOH CH 2
NH 2
C¡«SCoA

O
 HEME SYNTHESIS STEPS…
2. Two ALA molecules condense together
to form phorpobilinogen catalyzed by
phorpobilinogen synthase or ALA
dehydratase
Step 2 COOH O

O H
CH 2
porphobilinogen
CH HO
2

O C ALA dehydratase
O

H C H

H N H
2H2O
N
H
H 2
N
 HEME SYNTHESIS STEPS…
3) Condensation of four phorpobilinogen
molecules to form uroporphyrinogen Ⅰ
catalyzed by
uroporphyrinogen-1synthase
PBG units are added to the dipyrromethane until a linear
hexapyrrole has been formed.
 HEME SYNTHESIS STEPS…
4. formation of uroporphyrinogen Ⅲ from
uroporphrinogen Ι catalyzed by
uroporphyrinogen-Ⅲ co-synthase
Uroporphyrinogen III synthase converts the linear tetrapyrrole
hydroxymethylbilane to the macrocyclic uroporphyrinogen III.
 HEME SYNTHESIS STEPS…
5. Coproporphyrinogen Ⅲ formation from
uroporphyrinogen Ⅲ catalyzed by
coproporphyrinogen decarboxylase
• The above four reactions from step 2 to step 5
occur in cytoplasm after that
coproporphyrinogen is transported back to
mitochondoria
6. Formation of protoporphyrin-Ⅸ from
coproporphyrinigen Ⅲ catalyzed by
coprophyrinogen oxidase
 HEME SYNTHESIS STEPS…
7. Protoporphyrin-Ⅸ is formed by the action
of protoporphyrinogen oxidase
8. Synthesis of HEME by insertion of ferrous
iron at the middle of protoporphyrin-Ⅸ
catalyzed by FERROCHELATASE or HEME
SYNT5HASE
 heme is formed by incorporation of iron (Fe+2)
 partly spontaneous
 ferrochelatase enhances rate
 inhibited by lead
 Fe++ is added to protoporphyrin IX via Ferrocheletase.
 URO

COPRO
PROTO
 HEMOGLOBIN…
• Globin protein folds around HEME to form
protective hydrophobic pocket
• In the absence of Globin Heme iron is
oxidized into ferric state and heme is changed
into HEMIN which inhibits ALA synthase.
• Ferric ions activate synthesis of globin
 REGULATION OF HEME synthesis

1. ALA SYNTHASE: HEME inhibits synthesis of

ALA synthase by repressing transcription
of the ALA synthase gene in most cells
• The feedback regulatory effect is end
product inhibition.
 REGULATION OF HEME synthesis…

• When there is excess HEME without globin

hematin is formed and hematin inhibits the
action of ALA synthase

• Lack of Vitamin B-6 decrease synthesis of

ALA
 REGULATION OF HEME synthesis…
• Porphobilinogen synthase or ALA
dehydratase contain zink and inhibited by
LEAD that results in high ALA level which
causes neurologic symptoms excess lead
due to its similarity to GABA
2. ALA Dehydratase and ferrochelatase are
inhibited by excess lead
3. Erythropoetin: low level production due to
kidney failure leads to low RBC synthesis
inturn decreases heme synthesis and low
erythropoetin also leads to anemia
 PORPHYRIA
• Metabolic disorder caused by accumulation of
porphryins due to decreased level of enzymes
involved in Heme synthesis which occurs genetic
diseases and the other cause of poryphria is due to
hepatic dysfunction and excess amount of lead
• Grouped into hepatic poryphria and erythropoetic
poryphria
 PORPHYRIA…
• Clinical manifestations includes
neurologic symptoms and skin symptoms
Biochemical causes of major sign and symptoms of porphyria
 HEME
CATABOLISM