Collagen synthesis structure and disorders. Flashcards
What is the structure of collagen?
Triple helix of amino acid chains of repeating Gly-X-Y amino acids. hydroxylated Proline and lysine are typically the X position.
Hydroxylation of the collagen fibres proline and lysine require what?
Vitamin C, deficiency leads to Scurvy.
What is Scurvy?
Vitamin C deficiency leading to reduced collagen hydroxylation.
What are the symptoms of Scurvy?
Petechiae surrounding hair follicles, Loose Teeth, Bleeding gums, Poor Wound healing, Poor bone development.
After hydroxylation the collagen fibres are Glycosylated, and then formed into triple helices (procollagen). In what condition is this defective?
Osteogenesis imperfecta.
What is Osteogenesis Imperfecta?
Genetic bone disorder leading to a defect in the formation of the triple helix collagen (procollagen)
The most common type is AD and has decreased production of collagen type 1.
Symptoms of Osteogenesis imperfecta?
Multiple fractures with minimal trauma (Brittle bones)
Blue sclerae
Skeletal deformaties,
Hearing loss and dental issues (Lack of dentin)
Once procollagen is formed, secreted and then propeptides are cleaved into insoluble tropocollagen.
Tropocollogen is then stabilised how?
Cross-linkage of lysine-hydroxylysine occurs via copper containing lysyl oxidase.
In what conditions is there a defect in cross linking the tropocollagen fibrils.
Ehler Danlos syndrome and Menkes.
What genes are implicated in Ehler Danlos syndrome
Lysine hydroxylase and collagen genes leading to defects in crosslinking collagen fibres.
Classic EDS has a mutation in type V collagen genes.
What are some symptoms of Ehler Danlos syndrome
Hyperextensible joints, fragile skin,
Hypermobile joints, dislocations
Varicose veins and ecchymoses.
Menkes disease is an X-linked recessive disorder due to deficiency in what?
Copper due to defective menkes protein.
This leads to decrease in lysine oxidase activity (as copper is a needed co-factor)
Symptoms of Menkes disease
Brittle, kinky hair, growth retardation and hypotonia.
What tissues have type 1 collagen?
Bone, Dentine, skin, tendons and fascia
What tissues contain type 2?
Cartilage - hyaline, vitreous body, nucleus pulposus
