MGD insulin & collagen Flashcards
how is insulin secretion regulated?
controlled by blood glucose levels
sensed by glucokinase ß-cells in pancreas
what is insulin? (structure)
a peptide hormone stabilised with 2 intra (3) disulphide bridges
secreted with C-peptide
how is C-peptide useful in diabetes?
in showing endogenous concentration of insulin produced
how is insulin produced?
- translation of pre-proinsulin into ER lumen and cleavage of signal sequence by signal peptidase
- folding of proinsulin and formation of disulphide bridges between A & B peptides (2 inter & 1 intra A)
- concentration and packaging into secretory vesicles in the golgi body
- proteolysis of C domain by proteases in vesicles to form insulin and C-peptide - all secreted together
structure of collagen (& overview of synthesis)
left handed, alpha triple helix:
3 chains modified in RER and come together to form procollagen
procollagen is cleaved outside the cell to form tropocollagen
tropocollagen laterally associates with others to form a collagen fibril
coming together to form collagen fibre
basic unit is tropocollagen
rich in glycine, hydroxyproline, hydroxylysine
v high tensile strength
How is collagen synthesised? (only steps in ER)
Cleavage of signal sequence by signal peptidase
Hydroxylation of proline/lysine via prolyl hydroxylase (add OH) - requires vit C & Fe2+
Addition of N-linked oligosaccharidesto asparagine residues in RER
Addition of galactose to hydroxylysine residue
Disulphide bridge formation through activity of PDI (protein disulphide isomerase)
Triple helix formation (right handed a1 & a2, C–> N terminus)
How is collagen synthesised? (only steps in golgi)
O-linked glycosylation
Golgi body secretion via exocytosis
(both in procollagen)
How is collagen synthesised? (only extracellular)
Into the ECM (extracellular membrane)
Removal of terminal domains (N+C)
Lateral association with covalent cross linking by lysyl oxidase (aggregation of fibrils) - side to side linkage, requires vit B6 & Cu2+
