clinical biochemistry exam 1 - collagen related diseases

describe beta sheets

• hydrogen bonding between adjacent peptide chains

• parallel or antiparallel

• exhbit right-handed twist 

describe alpha helices

• repeating spiral, righthanded

• little steric hindrance

• forms repeated hydrogen-bonds along backbone

what is the secondary structure of collagen

3 left-handed helicies form a right-handed triple helix configuration

which amino acids are involved in the synthesis of collagen

proline and lysine which are hydroxylated to form hydroxyproline and hydroxylysine

what is the amino acid composition of collagen structure 

1/3 gly, 15-30% pro or hyp

what does the presence of hyp do for the collagen structure

confers stability through intramolecular hydrogen bonds that involve bridging water molecules

what amino acid can lie near the center of the triple helix and why

gly because all other amino acids are too bulky

what is the purpose of the pro in collagen

prevents formation of an alpha helix so the collagen polypeptide assumes a left-handed helical conformation

how are the collagen chains cross-linked

• covalently through links between lys and his side chains near the N and C terminals

what is scurvy

deficiancy of vit c which leads to deficiancy of ascorbic acid

how does ascorbic acid affect collagen formation

Hyp is needed for collagen stability, ascorbic acid is used to make Hyp if there is a deficiancy of vit c (ascorbic acid) then the collagen structure doesnt form properly

what does ascorbic acid do

reduces iron so thatit can continue to serve as a cofactor for proline and lysyl hydroxylases

in the case study what was the treatment for the pt with scurvy

vit c and iron

what happens if collagen is not properly hydroxylated 

• ER stress

• misfolded procollagen

• weaker collagen fibers

what is “brittle bone diease”

• autosomal dominant genetic disease that affects the bones

what are the clinical features of brittle bone diease

• fragility of bones

• pale blue sclera and deafness

• abnormal shape of skull and ligaments 

what is the biochemical abnormality of brittle bone disease

frequently defective synthesis of type 1 collagen

how many a2 and a1 chains does a normal collagen helix have

2 a1 and 1 a2

what is a ‘null allele’ mutation for brittle bone diease

mutations in COLA1 in which the cells make half of normal amount of collagen; if mutations in COLA2 collagen has 3 a1 chains

what is a structural mutation for brittle bone disease

either gene produces abnormal type 1 collagen

what leads to structural mutations that lead to brittle bone disease and what do they do

subsitutions of another amino acid leads to affects on

• protein stability

• slower folding

• post translational over modifications 

how can changes to collagen structure be detected

using differential scanning calorimetry

what are bisphosphonates used for

increasing bone density and thickness; prevent tumors from removing bone and spreading

how are bisphophonates used for OI (brittle bone disease)

• reduce fractures and enhance longitidinal bone growth

• block mevalonte pathway inhibits osteoclast activity and hence helps preserve bone

• doesn’t improve collagen synthesis

what are the three drugs used for OI

1. anti-resorptive (bisphosphonates): control osteroclats

2. anabolic: stimulate osteroclats

3. dual