Structure
- Collagen is one of the four major components of connective tissue.
- It forms 25-35% of the total body protein weight.
- Tropocollagen is the structural unit of collagen which consists of 3 alpha chains in a right-handed triple helical structure held together by hydrogen bonds- homotrimeric or heterotrimeric.
- Proline, hydroxyproline and glycine are helix destabilizing amino acids which prevent the formation of alpha-helical and beta-pleated structure.
- Based on the different helical combinations, 28 distinct collagens are found of which Type I is the most abundant
- Amino Acid composition of collagen:-
- Glycine- 33%
- Proline- 10%
- Hydroxyproline- 10%
- Hydroxylysine- 1%
- Regular arrangement of amino acid residues is 3 per turn in the pattern of Glycine-X-Y where X and Y are other amino acids, mostly proline and hydroxyproline.
- Glycine, being the smallest amino acid, is the only amino acid small enough to be accommodated inside the limited space of core of helix and is hence found in every third position of the polypeptide chain.
- Individual tropocollagen molecules aggregate laterally by overlapping approximately a third of their neighbor.
- They arrange into quarter staggered, parallel and overlapping array structures.
- The regularity of gaps and overlaps generates the banded appearance of collagen fiber.
- The fibrillar array are stabilized by the following inter and intra crosslinks with the help of copper requiring enzyme lysyl oxidase:-
- Aldol condensation
- Schiff Base
- Lysinonorleucine
- These crosslinks along with hydroxylation of proline and lysine provide tensile strength to collagen and prevent it from stretching
Disorders
- Ehlers-Danlos Syndrome(EDS)-
- Genetic disorder
- Caused by mutation in COL5A1 and COL5A2 genes encoding alpha-1 and alpha-2 chains of Type V collagen
- Hyperextensibility of Skin
- Hypermobility of joints
- Fragile Skin
- Laxity in Musculo skeleton
- Alport Syndrome-
- Defect in formation of Type IV collagen fibres
- Hematuria and Renal disease
- Osteogenesis Imperfecta-
- Brittle bone syndrome
- Mutation in COL1A1 and COL1A2 genes which code for two chains of Type-I Collagen.
- Glycine is substituted by Cysteine.
- Brittle bones, thin skin, abnormal teeth, and weak tendons
- Sclera abnormally thin, translucent, blue.
- Scoliosis and hearing loss
- Epidermolysis bullosa(EB)-
- Genetic- Mutation in COL7A1 gene encoding Type VII collagen responsible for anchoring basal lamina to dermis.
- Anchoring filaments are reduced causing skin breaks
- Blistering of skin and epithelial tissue
- Scurvy-
- Nutritional disorder, Vitamin C deficiency
- Vitamin C is required for prolyl hydroxylase and lysyl hydroxylase in collagen biosynthesis
- Abnormal bone development in infants and children
- Loosening of teeth
- Swollen bleeding gums
- Poor wound healing
- Easy bruising and subcutaneous hemorrhage due to fragile capillaries.
- Lathyrism-
- Dietary disease due to inhibition of Lysyl oxidase by compounds like BAPN (Beta Amino Propionitrile) and BOAA (Beta Oxalyl Amino Alanine) found in Sweet Pea(Lathyrus odoratus)
- Lysyl oxidase is required for cross linking of collagen chains.
- Deformation of spine
- Demineralization of bone
- Dislocation of joints
- Aortic aneurism
- Fragility and weakness of Skin, Blood vessels, and bone.