HEMOGLOBIN AND

MYOGLOBIN STRUCTURE
AND FUNCTION
Abdul Musasizi
MBChB 1.1

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 1

 HEMEPROTEINS
• Group of specialized proteins that contain heme as a
tightly bound prosthetic group
• Heme is a complex of protoporphyrin IX and ferrous iron
(Fe2+)
• Hemoglobin and Myoglobin are the most abundant
heme proteins in humans
• The heme group group serves to bind reversibly with
oxygen.

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 2

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 4
 Myoglobin
• Hemeprotein present in heart and skeletal muscle.
• Consists of a single polypeptide chain structurally
similar to the a subunit polypeptide chains of the
hemoglobin molecule.
• It is a reservoir for oxygen by binding it to iron atom.
• An oxygen carrier thus increases the rate of transport of
oxygen within the muscle cell.

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 5

 Myoglobin Structure
• Compact molecule, with approximately 80% of its polypeptide
chain folded into eight stretches of α-helix
• Myoglobin is composed of a single polypeptide chain of 153
amino acid residues.
• Interior of the molecule is composed almost entirely of nonpolar
amino acids
• The structure is stabilized by hydrophobic interactions between
these clustered residues
• Charged amino acids are located almost exclusively on the
surface of the molecule, w
• They form hydrogen bonds, both with each other and with
water.
10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 6
10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 7
 Structure and bonding
• Heme group is a flat ring molecule containing carbon, nitrogen
and hydrogen atoms, with a single Fe2+ ion at the center.
• In a heme molecule, the iron is held within the flat plane by four
nitrogen ligands from the porphyrin ring.
• The globin portion provides an environment for the heme that
can bind only one oxygen molecule.
• It has eight alpha helices and a hydrophobic core.
• There is a proximal histidine group attached directly to the Iron
centre.
• A distal histidine group exists on the opposite face, not bonded
to the iron, but it stabilizes the binding of oxygen to the iron.
10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 8
 Haemoglobin
• Found exclusively in red blood cells
(RBCs)
• Functions to transport oxygen from the
lungs to the capillaries of the tissues
• Haemoglobin A, the major haemoglobin
in adults.
• It is a tetrameric protein
• Composed of four polypeptide chains ;-
two α chains and two β chains held
together by non-covalent interactions

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 9

 Structure and Bonding
• Composed of two identical dimers, (αβ)1 and (αβ)2
• The polypeptide chains within each dimer are held
tightly primarily by hydrophobic interactions
• Interchain hydrophobic interactions form strong
associations between α-subunits and β-subunits in the
dimers
• Ionic and hydrogen bonds also occur between the
members of the dimer

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 10

 Forms of Haemoglobin
T,” or taut(tense) form R (relaxed) form
• Deoxy form of hemoglobin • Oxy form of haemoglobin
• The two αβ dimers interact • Binding of oxygen to
through ionic bonds and hemoglobin causes the
hydrogen bonds. rupture of some of the ionic
• T form is the low oxygen- bonds and hydrogen bonds
affinity form of hemoglobin. between the αβ dimers.
• R form is the highoxygen-
affinity form of hemoglobin

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 11

 T - form R - form

Deoxy State Oxy state

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 12

 Myoglobin

• Myoglobin can bind one molecule of oxygen, because it contains one

heme group.

• The oxygen disassociation curve is Hyperbolic for Mb.

• It means that Mb has high affinity for oxygen at all pO2.

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 13

• pO2 needed to achieve half saturation of the binding site is approx: 1
mm of Hg.
( 26 mm of Hg -Hb).

• Advantage: Mb can bind O2 released by the Hb in the tissues at low

pO2, and then release it within the muscle cell in response to O2
demand.

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 14

• High concentrations of myoglobin in muscle cells allow organisms to
hold their breaths longer.

• Oxygen binds to myoglobin and is released only when the hemoglobin

can no longer supply adequate oxygen to muscle cells.

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 15

 Differences
Haemoglobin Myoglobin
Tetrameric protein Monomeric protein
2-alphas 141aas & 2-beta 146aas 153aa residues
Four heme groups A single heme group
Sigmoid Oxygen dissociation curve Hyperbolic
Binds to four Oxygen molecules Binds to a single Oxygen molecule
Saturation at high pO2 Saturation at low pO2
Exclusively in RBCs Located mainly in very active
tissues

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 16

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 17
 HEMOGLOBINOPATHIES
• Genetic disorders caused by production of a structurally
abnormal haemoglobin molecule, synthesis of insufficient
quantities of normal haemoglobin.
• Sickle cell anemia (Hb S)
• Hemoglobin C disease (Hb C) (lysine)
• Hemoglobin SC disease (Hb S + Hb C)
• Thalassemia syndromes
• Qualitative hemoglobinopathy result from production of
hemoglobin with an altered amino acid sequence
• Quantitative hemoglobinopathy are caused by decreased
production of normal haemoglobin e.g. thalassemias

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 18

 Hemoglobin S disease
• A genetic disorder of the blood caused by a single nucleotide alteration
(a point mutation) in the gene for β-globin.
• Most common inherited blood disorder in the United States, affecting
80,000 Americans
• Sickle cell anaemia is a homozygous, recessive disorder.
• Occurs in individuals who have inherited two mutant genes (one from
each parent) that code for synthesis of the β chains of the globin
molecules.
Note: The mutant β-globin chain is designated βS, and the resulting
hemoglobin, α2βS2, is referred to as Hb S
• HbS is characterized by lifelong episodes of pain (“crises”), chronic
hemolytic anemia with associated hyperbilirubinemia, and increased
susceptibility to infections, usually beginning in early childhood.
Note: Lifetime of erythrocyte in sickle cell anemia is less than 20 days,
compared with120 days for normal RBCs
10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 19
 Hemoglobin S disease
More symptoms…,
• A molecule of Hb S contains two
• Acute chest syndrome normal α-globin chains and two
• Stroke mutant β-globin chains (βS), in
which glutamate at position six has
• Splenic and renal been replaced with valine.
dysfunction, • At low oxygen tension,
• Bone changes due to deoxyhemoglobin S polymerizes
marrow hyperplasia inside the RBC
• A network of fibrous polymers that
stiffen and distort the cell,
producing rigid, misshapen
erythrocytes.
10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 20
 Treatment
• Adequate hydration
• Analgesics
• Aggressive antibiotic therapy if infection is present.
• Transfusions in patients at high risk for fatal occlusion of blood vessels.
• GENE THERAPY….BONE MARROW TRANSPLANT RESEARCH IS
ON!
• Intermittent transfusions with packed red cells reduce the risk of stroke
• Hydroxyurea, an antitumor drug, is therapeutically useful because it
increases circulating levels of Hb F, which decreases RBC sickling
Note: A selective advantage exists for heterozygotes for the sickle cell
gene that makes them less susceptible to malaria, caused by the parasite
Plasmodium falciparum.
10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 21
 Thalassemias
• These are hereditary hemolytic diseases in which an imbalance occurs in
the synthesis of globin chains
• In the thalassemias, the synthesis of either the α- or the β-globin chain is
defective
• Caused by a variety of mutations; entire gene deletions, substitutions or
deletions of one to many nucleotides in the DNA.

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 22

Role in disease
• Myoglobin is released from damaged muscle tissue (rhabdomyolysis),
which has very high concentrations of myoglobin.

• The released myoglobin is filtered by the kidneys but is toxic to the

renal tubular epithelium and so may cause acute renal failure.

10/11/2019 SAIU BIOCHEMISTRY DEPARTMENT 23