MYOGLOBIN

SUBMITTED BY:
SAKSHI SHARMA
ROLL NO.-5855
SECTION-B, 3RD YEAR
 CONTENTS

INTRODUCTION
HISTORY
STRUCTURE
HEME GROUP
MECHANISM
FUNCTION
COMPARISON B/W Hb AND Mb
ROLE IN DISEASE
 INTRODUCTION

 Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in

the muscle tissue of vertebrates in general and in almost all mammals. It is
distantly related to hemoglobin which is the iron- and oxygen-binding protein
in blood, specifically in RBC’s. Myoglobin is the primary oxygen-carrying
pigment of muscle tissues.[7] High concentrations of myoglobin in muscle cells
allow organisms to hold their breath for a longer period of time. Diving
mammals such as whales and seals have muscles with particularly high
abundance of myoglobin.[6] Myoglobin is found in Type I muscle, Type II A,
and Type II B, but most texts consider myoglobin not to be found in smooth
muscle.
 HISTORY

 In 1897 Mörner described a red protein in muscle, which he called

“myochrome”.
 Early studies of myoglobin are considered to be where the science of
protein structure began. John Kendrew and his coworkers determined
the atomic structure of sperm whale myoglobin, making it the first
protein to have its three dimensional structure revealed by X-ray
crystallography. This feat earned Kendrew the Nobel Prize in 1962,
shared with Max Perutz who revealed the structure of hemoglobin
(Kendrew et al. 1958, Perutz et al. 1960, and Watson and Kendrew
1969).
 STRUCTURE

 Myoglobin is a monomeric protein that has 154 amino acids residues. It

consists of eight α-helicies connected through the turns with an Oxygen
binding site. It has a globular structure. Myoglobin contains a heme
(prosthetic) group which is responsible for its main function (carrying of
oxygen molecules to muscle tissues). Myoglobin can exist in the oxygen
free form, deoxymyoglobin, or in a form in which the oxygen molecule is
bound, called oxymyoglobin. Myoglobin is a protein found in muscles that
binds oxygen with its heme group like hemoglobin.

This is an image of an oxygenated myoglobin

molecule. The image shows the structural change
when oxygen is bound to the iron atom of the
heme prosthetic group. The oxygen atoms are
Myoglobin 3D structure
colored in green, the iron atom is colored in red,
and the heme group is colored in blue.
 HEME GROUP
 Heme group consists of protoporphyrin organic component and an iron atom
located in its center. The heme group gives muscle and blood their distinctive
red color. The organic component consists of four pyrrole rings that are linked
by methine bridges. In addition, heme is responsible for the red color of the
blood and muscle. Oxidation of the iron atom (Fe2+ -> Fe3+) is mainly
responsible for the color of muscle and blood. At the center of protporphyrin,
the iron atom is bonded to nitrogen atoms from four pyrrole rings. The iron
atom can form two additional bonds, one on each side of the heme plane.
These binding sites are called the fifth and sixth coordination sites.

Heme group molecular structure

 .

 In myoglobin, the fifth coordination site is occupied by the

imidazole ring from a histidine residue on the protein. This
hisitidine is referred to as the proximal histidine. The sixth
coordination site is available to bind oxygen. The iron atom in
deoxymyoglobin lies about four angstroms out of the plane of
the protoporphyrin plane because it is too big in that form to
fit into the well defined hole.

MYOGLOBIN MOLECULAR
STRUCTURE
 MECHANISM
 Myoglobin contains a Fe(II) cation bound to a heme group, which gives it the ability to
bind to oxygen reversibly. The normal oxidation state of an iron atom has a positive
two charge (ferrous ion) instead of three charge (ferric ion) and it is too large to fit
into the plane of protoporphyrin. Thus, a ferrous ion is often 0.4 Å away from the
porphyrin plane. However, when iron oxidized from ferrous ion (Fe 2+) to ferric ion
(Fe3+), because the loss of one extra electron, forces between protons and electrons
increases so that the electron cloud will penetrate more towards to the nucleus. As a
result, the ferric ion (Fe3+) has a smaller size then ferrous ion (Fe2+) and fits into the
protoporphyrin plane when it attaches to an oxygen.
When oxygen leaves the myoglobin, it leaves as dioxygen rather than superoxide.
This is because superoxide can be damaging to many biological process, and in the
leaving of superdioxide, the iron ion will be in the ferric state which stops biding
oxygen. to bind to oxygen reversibly.

The interaction between myoglobin and

oxygen included the resonance of iron (II)
ion with oxygen and iron (III) ion with
superoxide ion
The distal histidine amino acid from the hemoglobin protein molecule further stabilizes
the O2 molecule by hydrogen-bonding interactions.
Molecular orbital description of Fe-O2 interaction in
myoglobin.
 FUNCTION

 Myoglobin, an iron-containing protein in muscle, receives oxygen from the red

blood cells and transports it to the mitochondria of muscle cells, where the
oxygen is used in cellular respiration to produce energy. Each myoglobin
molecule has one heme prosthetic group located in the hydrophobic cleft in the
protein. The function of myoglobin is notable from Millikan's review in which
he put together an accomplished study to establish that myoglobin is formed
adaptively in tissues in response to oxygen needs and that myoglobin
contributes to the oxygen supply of these tissues. Oxymyoglobin regulates both
oxygen supply and utilization by acting as a scavenger of the bioactive molecule
nitric oxide. Nitric oxide is generated continuously in the myocyte .
Oxymyoglobin reacts with NO to form harmless nitrates, with concomitant
formation of ferric myoglobin, which is recycled through the action of the
intracellular enzyme metmyoglobin reductase. Flogel conducted a study that
showed how the interaction of NO and oxymyoglobin controls cardiac oxygen
utilization.
Myoglobin Binding Curve
 COMPARISON B/W Hb AND Mb
BASIS FOR COMPARISON HEMOGLOBIN MYOGLOBIN
Number of chains Haemoglobin has It contains single polypeptide chains.
4 chains of two
different types-
alpha and beta,
delta, gamma, or
epsilon
(depending on
the type of
hemoglobin).
Type of structure A tetramer. A monomer.
Binds Binds CO2, CO, Binds to O2, tightly and firmly.
NO, O2 and H+.
Their presence Systemically all In muscles cells.
over the body.

Types of curve Sigmoid binding Hyperbolic curve.

curve.
Also known as Hb. Mb.

Role Haemoglobin is Myoglobin supplies oxygen to muscles only,

transported along which is helpful at the starving time of oxygen.
with blood to
whole body and
carry oxygen.

Concentration in blood High in RBC. Low.

.
 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 kidney injury. It is not the myoglobin itself that is toxic (it is a
protoxin) but the ferrihemate portion that is dissociated from myoglobin in
acidic environments (e.g., acidic urine, lysosomes).
 Myoglobin is a sensitive marker for muscle injury, making it a potential
marker for heart attack in patients with chest pain. However, elevated
myoglobin has low specificity for acute myocardial infarction (AMI) and thus
CK-MB, cardiac Troponin, ECG, and clinical signs should be taken into
account to make the diagnosis.

RHABDOMYOLYSIS
 .

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