Transcript FIBROUS PROTEINS

FIBROUS PROTEINS
BY
DR.MARYJANE
INTRODUCTION
• Collagen and elastin are examples of fibrous
proteins that have structural functions in the
body.
• For example, collagen and elastin are found as
components of skin, connective tissue, blood
vessel walls, sclera and cornea of the eye.
COLLAGEN
• Collagen is the most abundant protein in the human body.
• Collagen provides strength and structure.
• Typical collagen molecule is a long, rigid structure in which
three polypeptides (referred to as α-chains) are wound
around one another in a rope like triple helix
• The three polypeptide α-chains are held together by
hydrogen bonds
• Amino acid sequence and composition:
• Collagen contains 33% glycine, 10% proline, 10%
hydroxyproline and 1% hydroxylysine.
TYPES OF COLLAGEN
TYPE
TISSUE DISTRIBUTION
I (most common type)
Skin, bone, tendon, blood vessels, cornea
II
Cartilage, vitreous body, intervertebral disk
III
Blood vessels, fetal skin
IV
Basement membrane
VII
Beneath stratified squamous epithelium
IX
Cartilage
XII
Tendon, ligaments, some other tissues
COLLAGEN DISEASES
• Scurvy: is due to a deficiency in ascorbic acid (vitamin C) required
for synthesis of collagen in humans.
• Symptoms include abnormal bone development, bleeding, loosing
of teeth and swollen gums.
• Osteogenesis imperfecta (OI): known as brittle bone syndrome it
is a genetic disorder characterized by bones that easily bend or
fracture, blue sclera, hearing loss, retarded wound healing
kyphosis, scoliosis (S-curve spine)
• Type I OI is called osteogenesis imperfecta tarda: this disease
presents in early infancy with fractures secondary to minor trauma
• It is a consequence of decreased production of α₁ and α₂ chains
• Type II OI called osteogenesis imperfecta congenita: is more
severe and patients die in utero
• Autosomal dominant disorder.
• It is due to a deficiency in collagen type I
OSTEOGENESIS IMPERFECTA
SCURVY
• Ehlers-Danlos syndrome: is a genetic disorder
that leads to connective tissue diseases.
Usually a deficiency of type I,III & V collagen
but most commonly type III
• Symptoms include: stretchy skin and loose,
hyperextensible joints, joint dislocation, easy
scarring and poor wound healing
• ELASTIN: it is a connective tissue protein
synthesized from the precursor tropoelastin which
is a linear polypeptide composed of about 700 small
non-polar amino acids(glycine, alanine, valine).
• Structure:.Elastin is rich in lysine and proline. It is
poor in hydroxyproline and hydroxylysine.
• Location: present in lungs, the walls of large blood
vessels and elastic ligaments.
• characteristic: It is rubber like i.e. it can be
stretched to several times but return to its original
shape when the stretching force is relaxed.
ROLE OF α₁-ANTITRYPSIN IN ELASTIN
DEGRADATION.
• α₁-antitrypsin is a protein secreted mainly by liver. It is
also secreted by blood cells monocytes and
macrophages.
• It is present in blood and other body fluids.
• It inhibits a number of proteolytic enzymes (proteases
or proteinases) that destroy proteins.
• Role of α₁-AT in the lungs: in the normal lung, the
alveoli are exposed to low levels of elastase enzyme
released from activated neutrophils whose proteolytic
activity can destroy the elastin in alveolar walls. This
elastase enzyme activity is inhibited by α₁-antitrypsin.
Deficiency of α₁-AT
• Leads to:
• Emphysema: which can be genetic or acquired
• Treatment: weekly intravenous administration
of α₁-AT
1-antitrypsin (1-AT) Deficiency
emphysema
• Emphysema is an autosomal recessive disorder
characterized by destruction of connective tissue
elastin of alveolar wall by the enzyme elastase due
to deficiency of α₁-antitrypsin called panacinar
emphysema OR due to cigarette smoking called
centrilobular emphysema.
• Normally elastin keeps the small airways open
when we exhale, but destruction of elastin results
in narrowing of the airway affecting exhalation such
that air in the lungs are not fully exhaled leading to
air trapping and hyperinflation of the lung
1. MARFAN SYNDROME: Connective tissue disorder.
– PATHOGENESIS: Mutation in the gene for FIBRILLIN,
which serves as a scaffold for the deposition of elastin.
– SYMPTOMS: Tall and slender
• SKELETAL:
– Arachnodactyly = spider finger, long fingers
– Hyperextensible, weak tendons and joints.
– Pectus excavatum or Carinatum
• CARDIOVASCULAR: Most common cause of death.
– DISSECTING AORTIC ANEURYSMS.
– Heart valvulopathies. (floppy valve syndrome)
• EYES: Connective tissue problems.
– Bilateral dislocation of lens (weakness of suspensory
ligament), severe myopia, retinal detachment.