3. Objectives Definition Different Types & their Functions Molecular Structure & Synthesis Role of vitamin C in Collagen synthesis Role of Collagen in wound repair Structural and Chemical changes in Collagen as grows older Abnormal Collagen synthesis: Diseases and genetic disorders 3
4. Definition Derived from Greek word “kolla” meaning Glue Producer” : any of a group of fibrous proteins that occur in vertebrates as the chief constituent of connective tissue fibrils and in bones and yield gelatin and glue upon boiling with water 4
5. Basic Information about Collagen Most abundant Fibrous protein (structural protein) in vertebrates 25% or more(up to 35%) of total body protein Major component of connective tissue Provides an extracellular framework for Strength & Flexibility At least 25 distinct types of Collagen 30 distinct types PP chains (each encoded by separate gene) 5
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7. As per latest research 29 types of collagen have been found.
11. Structure of Collagen Collagen has a most unusual amino acid composition in which Glycine, Proline, Hydroxyproline, Lysine & Hydroxylysine are dominant. 10 Glycine
15. The three collagen chains do not form Hydrogen bonds among residues of the same chain. Instead, the collagen chains within each three stranded cable form interchain Hydrogen bonds. This produces a highly interlocked fibrous structure that is admirably suited to its biological role, which is to provide rigid connections between muscles and bones as well as structural reinforcement for skin and connective tissue. 15 From the book:-Analytical Biochemistry - David Holme, Hazel Peck
16. Collagen fibrils consist of recurring three-stranded polypeptide units called tropocollagen, arranged head to tail in parallel bundles. Between the polypeptide strands of the triple helix covalently bonded molecular bridges are erected by a series of reactions that cause Lysine side chains to link together. Part of the toughness of collagen is due to the cross linking of tropocollagen molecules to one another via a reaction involving lysine side chains. These cross links form through the lysyl oxidase. 16
17. This process (of forming cross links through the action of Lysyl oxidase) is continuous throughout the life leading to the accumulation of cross links. This accumulation is usually associated with changes seen in aging like brittle bones and loss of elasticity of the skin. In addition to this, collagen as one ages, becomes less organized and causes loss of skin turgor. 17
20. Collagen is initially synthesized as a larger precursor polypeptide, procollagen. Numerous prolyl and lysyl residues of procollagen are hydroxylated by prolylhydroxylase and lysylhydroxylase, enzymes that require ascorbicacid (vitamin C). Hydroxyprolyl and hydroxylysyl residues provide additional hydrogen bonding capability that stabilizes the mature protein. In addition, glucosyl and galactosyltransferases attach glucosyl or galactosyl residues to the hydroxyl groups of specific hydroxylysyl residues. Registration peptides on amino and carboxyl ends of the alpha chain which serves as extensions (contains Cys) 20
21. The central portion of the precursor polypeptide then associates with other molecules to form the characteristic triplehelix. This process is accompanied by the removal of the globular amino terminal and carboxyl terminal extensions of the precursor polypeptide by selective proteolysis (Procollagen peptidase/Procollagen aminoproteinase/Procollagen carboxyproteinase). 21
22. Certain lysyl residues are modified by lysyloxidase, a copper-containing protein that converts ε-amino groups to aldehydes. The aldehydes can either undergo an Aldol condensation to form a C=C double bond or to form a Schiffbase (eneimine) with the ε-amino group of an unmodified lysyl residue, which is subsequently reduced to form a C-N single bond. These covalent bonds cross-link the individual polypeptides and imbue the fiber with exceptional strength and rigidity. 22
43. The conversion involves a reaction that substitutes a hydroxyl group, OH, for a hydrogen atom, H, in the proline residues at certain points in the polypeptide chains, converting those residues to hydroxyproline. This hydroxylation reaction secures the chains in the triple helix of collagen. The hydroxylation, next, of the residues of the amino acid lysine, transforming them to hydroxylysine, is then needed to permit the cross-linking of the triple helices into the fibers and networks of the tissues. These hydroxylation reactions are catalyzed by two different enzymes: prolyl-4-hydroxylase and lysyl-hydroxylase. Vitamin C also serves with them in inducing these reactions. 33
44. Elemis Pro-Collagen Marine Cream 100ml Elemis Pro-Collagen Marine Cream 100ml is clinically proven to reduce the appearance of wrinkle depth by 78% and increase hydration and moisture levels by up to 45%£125.00 34
45. Ascorbic acid can also stimulate collagen synthesis by other mechanisms, it can induce lipid peroxidation and reactive aldehydes, which is a step required for collagen expression. Collagen gene expression is probably influenced by lipid peroxidation, or through acetaldehyde formation, which consequently increases collagen gene transcription in cultured human fibroblasts 35
46. UsesofCollagen History:- From the Greek for glue, kolla, the word collagen means "glue producer". Collagen adhesive was used by Egyptians about 4,000 years ago, and Native Americans used it in bows about 1,500 years ago. The oldest glue in the world, carbon-dated as more than 8,000 years old, was found to be collagen — used as a protective lining on rope baskets and embroidered fabrics, and to hold utensils together; also in crisscross decorations on human skulls. 36
47. Industrialuses If collagen is partially hydrolyzed, the three tropocollagen strands separate into globular, random coils, producing gelatin, which is used in many foods, including flavored gelatin desserts. Besides food, gelatin has been used in pharmaceutical, cosmetic, and photography industries. Animal glues are thermoplastic, softening again upon reheating, and so they are still used in making musical instruments such as fine violins and guitars. 37
48. Medicaluses:- Collagens are widely employed in the construction of artificial skin substitutes used in the management of severe burns & beauty treatments. (These collagens may be derived from bovine, equine or porcine, and even human sources and are sometimes used in combination with silicones, glycosaminoglycans, fibroblasts, growth factors and other substances) 38
60. Scurvy Gly –X- Y (Y = 4-hydroxyproline) Enzyme : propyl-4-hydroxylase Co-factor: Vit. C. Due to Vit C deficiency (impaired synthesis of collagen due to deficiencies of prolyl and lysyl and lysyl hydroxylases) Characteristics- - bleeding gum - delayed wound healing 49
