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 TYPETISSUE DISTRIBUTION I (most common type)Skin, bone, tendon, blood vessels, cornea IICartilage, vitreous body, intervertebral disk IIIBlood vessels, fetal skin IVBasement membrane VIIBeneath stratified squamous epithelium IXCartilage XIITendon, 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 α ₁ and α ₂ 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.