Collagen & Elastin Lecture Notes PDF

# Collagen & elastin ## Your Patient A 28 year old tall and slender build man is brought to an OPD with shortness of breath and early arthritis. On physical examination disproportionately long arms, legs, fingers, flat feet and abnormal curved spine was found. What's wrong with that man? ## Learn...

# Collagen & elastin ## Your Patient A 28 year old tall and slender build man is brought to an OPD with shortness of breath and early arthritis. On physical examination disproportionately long arms, legs, fingers, flat feet and abnormal curved spine was found. What's wrong with that man? ## Learning Objectives By the end of this lecture students will be able to know: - What are fibrous proteins and their importance. - Difference between fibrous and globular proteins. - Collagen and elastin, types, structure, synthesis and function. - Diseases associated with collagen and elastin. ## Fibrous Proteins - A Fibrous protein is a protein with an elongated shape, form 'rod' or 'wire' -like shapes and are usually inert structural or storage proteins. - Globular proteins are spiral and helical, linked by disulfide and hydrogen bond. - E.g. keratin, myosin, elastin & collagen (fibrous) ## Functions of Fibrous Proteins - Provide structural support for cells and tissues. - Used to construct connective tissues, tendons bone and muscle fiber. - Special types of helices present in two fibrous proteins α-keratin and collagen. - Form long fibers that serve a structural role in the human body. ## Fibrous vs. Globular Proteins | Feature | Fibrous | Globular | |----------------|-------------------|----------------| | Shape | Long and narrow | Round / spherical | | Purpose | Structural | Functional | | Acid Sequence | Repetitive amino acid sequence | Irregular amino acid sequence | | Durability | Less sensitive to changes in pH, temperature, etc. | More sensitive to changes in pH, temperature, etc. | | Examples | Collagen, myosin, fibrin, actin, keratin, elastin | Enzymes, haemoglobin, insulin, immunoglobulin | | Solubility | (Generally) insoluble in water | (Generally) soluble in water | ## Collagen & elastin - Collagen and elastin are well-characterized fibrous proteins, serve structural functions in the body. - Found as - components of skin - connective tissue - blood vessel walls - sclera, cornea. ## Collagen - The most abundant protein in the human body (25%). - Collagen molecule is a long, rigid structure in which three polypeptides "α-chains" are wound around one another in a rope-like fashion ## Types of Collagen | Type | Tissue Distribution | Description | |------|-------------------------------------------------------------|--------------------------------------------------------------------------------------| | I | Skin, bone, tendon, blood vessels, cornea | Forming rope like structure, linear polymers of fibrils have banding pattern | | II | Cartilage, intervertebral disk, vitreous body | | | III | Blood vessels, fetal skin | | | IV | Basement membrane | Network-forming, form a 3D mesh | | VII | Beneath stratified squamous epithelia | | | IX | Cartilage | Fibril-associated, linking fibrils to one another and to other components of ECM | | XII | Tendon, ligaments, some other tissues | | ## Structure of Collagen 1. **Amino acid sequence** - Rich in proline and glycine, they are important in the formation of the triple-stranded helix. - Proline facilitates the formation of the helical conformation of each α-chain because its ring structure → "kinks" in the peptide chain. - Glycine, is found in every third position of the polypeptide chain. - It fits into the restricted spaces where the three chains of the helix come together. ## Triple-Helical Structure - Collagen has elongated, triple-helical structure - Hydroxyproline & hydroxylysine - Present in collagens, not on other proteins - Result from hydroxylation after incorporation in to polypeptide chains. Hydroxyproline involve in stabilizing the triple-helical structure (interchain hydrogen bond formation -maximizes) ## Importance of Vitamin C - These hydroxylation reactions require molecular oxygen and the reducing agent vitamin C. - Why Vit C is needed? Hydroxylating enzymes prolyl hydroxylase and lysyl hydroxylase, are UNABLE to function without vit. C ## Vitamin C Deficiency - In the case of vit.C deficiency (↓prolyl and lysyl hydroxylation), collagen fibers cannot be cross-linked, greatly →↓↓ the tensile strength of the assembled fiber. - Vit.C deficiency → disease known as scurvy. - Patients with vit.C deficiency often show bruises on the limbs as a result of subcutaneous extravasation of blood (capillary fragility) ## Synthesis of Collagen - Synthesis: Precursor molecule formed in fibroblasts (osteoblasts of bone & condroblast of cartilage) & secreted in to ECM. - Enzymatic modification mature collagen monomers aggregates → cross linked →collagen fibril ## Diseases Associated with Collagen - Defects in any one of the many steps in collagen fiber synthesis → genetic disease → inability of collagen to form fibers properly provide tissues with the needed tensile strength ## Ehlers-Danlos Syndrome (EDS) - ↓ lysyl hydroxylase or procollagen peptidase - Mutation in the AA sequence of collagen types I, III or V ## Osteogenesis Imperfecta (OI) - Also known as brittle bone syndrome, a heterogeneous group of inherited disorders distinguished by bones. - Retarded wound healing and a rotated and twisted spine → 'humped-back" appearance are common features ## Different Types of Osteogenesis Imperfecta - **Type I** Mild to moderate bone fragility, kyphoscoliosis, hearing loss, easy bruising, short stature. - **Type II** Neonatal lethal; multiple in utero fractures. Patient usually dies of pulmonary hypoplasia in utero or during the neonatal period. - **Type III** Infant often born with fractures. The whites of the eyes may be white, blue, purple, or gray. People with type III osteogenesis imperfecta are generally shorter than average. They may have spinal deformities, respiratory complications, and brittle teeth. ## Elastin - Connective tissue with rubber-like properties. - Tough and tensile strength. - Found in the lung, the wall of large arteries & elastic ligaments. - Can be stretched to several times their normal length recoil to original shape when stretching force is relaxed. ## Marfan Syndrome - A genetic disorder that affects the body's connective tissue. - Results in abnormalities in the skeletal, cardiovascular, and ocular systems - Characterized by tall stature with long arms and legs, abnormally long fingers, chest deformities, and eye problems, particularly a dislocation of the lens of the eye. ## Summary of Fibrous Proteins - **Collagen:** The most abundant protein in the human body. It provides structural support for cells and tissues. - **Types:** There are 28 distinct types of collagen, each with a specific structure and function. - **Structure:** Collagen is made up of three polypeptide chains that are wound around each other in a rope-like fashion. - **Diseases:** Defects in collagen synthesis can lead to a variety of diseases, including Ehlers-Danlos syndrome and osteogenesis imperfecta. - **Elastin:** A protein that provides elasticity to tissues. It is found in the lungs, arteries, and skin. - **Structure:** Elastin is made up of a single polypeptide chain that is cross-linked to form a network. - **Diseases:** Defects in elastin synthesis can lead to diseases such as Marfan syndrome.