Collagen and Proteoglycans Flashcards
Discuss the genetics of collagen and what fibrillar collagens are
About 40 genes encode polypeptides that make up around 29 different types of collagen proteins in humans. Ten of these types are fiber-forming, so-called “fibrillar collagens.”
All fibrillar collagen genes contain exactly 42 exons each. The genes vary in overall length due to differences in intron sizes
All have a central region that encodes a 1014 amino acid stretch with the repeating unit: (Gly-X-Y)338
Discuss the general structure of collagen
All types contain 3 long polypeptide chains, with at least one stretch wound together to form a triple-helix.
Collagens are glycoproteins, but the amount of carbohydrate
is highly variable
Discuss glycine and hydroxyproline as they relate to collagen structure
Glycine residues are shoved to the middle of the collagen. Every third residue must be Gly since there is no room near the helix axis for the side chain of any other amino acid
Defects that produce collagen
lacking hydroxyproline can drop the melting point to 27 deg C or lower.
What are the two enzymes that cleave procollagen and what locations do they hit?
Aminoprocollagen peptidase cleaves the N terminal propeptide off and Carboxylprocollagen peptidase cleaves the C Terminal propeptide off.
Failure to remove N-terminal domain due to defective N-terminal peptidase results in
Ehlers-Danlos type VII
The first step of collagen synthesis involves hydroxylating proline and lysine residues. What enzymes do these?
Proline residues get hydroxylated (add -OH) by Prolyl Hydroxylase.
Lysine residues get hydroxylated by Lysyl Hydroxylase.
Both types need ascorbic acid.
Deficiency of lysyl hydroxylase gives you ED Type IV, and deficiency of ascorbic acid gives you scurvy
What happens after you hydroxylate the residues on collagen?
You slap sugars on those -OHs (glycosylate them), slap three together, make a triple helix and viola, procollagen.
How do we bind collagen so tightly?
For this, we need to oxidize our lysine residues to allysine, which reacts with a lysine to make a schiff base. Two allysines can also aldol condensate to make lysineorleucine (correct spelling)
What are proteoglycans and what do they do?
Proteoglycans (formerly called mucopolysaccharides) are
highly osmotically active extracellular polymers with gel-like properties that protect cells and provide tissues with mechanical resiliency
Hurler Syndrome
Autosomal recessive disorder caused by a deficiency of α-L-iduronidase, resulting in abnormal intra-lysosomal accumulation of dermatan and
heparan sulfate leading to cell death and organ dysfunction.
How do Hurler patients present?
Characterized by developmental delays, mental retardation, coarse facial
features with macroglossia, skeletal abnormalities, organomegaly, cardiovascular disease with valvular dysfunction, joint stiffness,
hydrocephalus, corneal clouding, umbilical and inguinal hernias.
