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TSM > 1.91 Biochemisty of Connective Tissue > Flashcards

1.91 Biochemisty of Connective Tissue Flashcards

1
Q

What gives hyaline cartilage its flexibility and resilience?

A

Proteoglycan content

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2
Q

What gives hyaline cartilage its rigidity and tensile strength?

A

Collagen Content

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3
Q

How does hyaline cartilage receive nutrients?

A

No nerve or blood supply

Receives nutrients via diffusion from synovial fluid, subchondral bone and perichondrium

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4
Q

What else is known about cartilage?

A

Immune privileged - break down of cartilage leads to autoimmune disease
Chondrocytes nutrient supply is slow - due to ECM
Accelerated diffusion - for nutrients
Immobilised joint – Hydroxyproline ­ in blood - collagen specific A.A.

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5
Q

What do chondrocytes release?

A

Chondrocytes release cytokines stimulating osteoclastogenesis

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6
Q

What do chondrocytes do when pressure is released?

A

Chondrocytes live inder pressure and if you release pressure they start to destroy even more ECM - released pressure due to damaged cartilage - release cytokines - stim breakdown of the bone below the cartilage

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7
Q

What collagen maid up of?

A
  • Unusual protein – 30% glycine, 30% proline/hydroxyproline; also contains hydroxylysine
  • Adult Articular cartilage consists of 2/3 by dry weight collagen
  • Made up of many Tropocollagen molecules aggregated together = insoluble
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8
Q

What gives collagen its properties?

A

Hydrogen bonding betweeen A.A - gives collagen its properties

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9
Q

How is pro collagen converted to tropocollagen?

A

Procollagen peptidases cut off the “two tails” - the n-terminal and c-terminal peptides (disulphide linked)

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10
Q

What is Elhers - Danlos syndrome type VII?

A

Stretchable skin, hyper-mobile joints and short stature - two tails not chopped off

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11
Q

What is tropocollagen made up off?

A

its a Type II Trans Helix
Hydrogen Bonds
Regular Composition
gly-x-x-gly-x-x-gly

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12
Q

Why does scurvy occur?

A

Vitamin c is required to convert proline into hoproline

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13
Q

Which amino acid is the smallest?

A

glycine

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14
Q

How many types of collagen is there?

A

I-XXIX

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15
Q

What stabilises collagen?

A

Covalent cross links - Aldol cross links - between aldehydes

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16
Q

What is Elhers - Danlos syndrome V?

A

Lysine oxidase - aldol cross link - if enzyme is missing or damaged - arteries would rupture as blood pulses through them - lack of cross links

17
Q

Which collagens are important in cartilage structure?

A

IX and XI

Mutations in COLIX and COLXI can result in Chondrodysplasia syndromes

18
Q

Which collagen is found in OA cartilage?

A

Collagen III localisation

19
Q

What are proteoglycans?

A

• Protein and glycan (polysaccharide)
• Special class of glycoproteins
• Usually low protein, High CHO
• Polysacch. Chains – glycosoaminoglycans
○ Joined by their reducing terminal sugar residues to the protein
Gives “bottle-brush” confirmation

20
Q

What is the “bottle brush structure made up of?

A

Protein core and GAG

21
Q

What are charge are Glycosaminoglycans?

A

Highly negatively charged (-OSO3-, -COO-) - sulphate and carboxylic groups

22
Q

What an Aggrecan?

A

Cartilage proteoglycan
Aggregates - negatively charged
Globular regions - G1,G2,G3 - G1 needed for aggregation

23
Q

What is keratan sulphate and what is it made from?

A 
Glycosaminoglycan 
Galactose 
1,4 linkage 
N-Acetylated 
GlcNac
24
Q

What is Chondroitin-6-sulphate?

A

Glycosaminoglycan
Glucorinic Acid - 1,3 linkage
GalNac - galactose + amine + n-acetylated
Very negative

25
Q

What are glycosaminoglycans?

A

Negative charge
Repeating disaccharides
Specific linkage region to the protein core

26
Q

How do aggrecan proteins aggregate?

A

• G1 – N-terminal globular region interacts with another glycosaminoglycan HYALURONAN [GlcUA - b1,3 – GlcNac]n
• Hyaluronan is NOT sulphated - in synovial fluid and vitreous fluid - protein core
Link protein - hyaluronan with proteoglycan
PWP?

27
Q

How are proteoglycans present in the ECM?

A

Most proteoglycans are present in the extracellular matrix as multimolceular aggregates - ionic interaction - stabilised by link proteins

28
Q

What do aggregates consist of?

A

• Aggregates consist of many proteoglycan monomers bound to a single molecule of hyaluronan by an IONIC interaction
This interaction is stabilised by link proteins, of which there are at least two (40,000 and 50,000 Mw)
Highly negatively charged (-COO-, -SO3-)
They retain large volumes of water in the extracellular matrix - due to negative charge

29
Q

What is a major function of aggregation?

A

The proteoglycans are immobilised in the collagen matrix as aggregate
The proteoglycans are restrained from swelling by the collagen meshwork “ a swelling pressure”
This arrangement gives cartilage its firm and flexible properties

30
Q

What would happen to the proteoglycans if collagen was removed?

A

• This arrangement gives cartilage its firm and flexible properties
• If the collagen was removed, the proteoglycans would expand and form a gel
• In fact, proteoglycans only occupy a fraction of their fully extended volume in the matrix
The hydrated proteoglycans can be REVERSIBLY COMPRESSED by displacement of some of the water from their hydration shells - overlapping of hydration shells - intermolecular repulsive forces

31
Q

What happens during redistribution of fluid from proteoglycans?

A

Redistrubude fljid within tissue - moves slowly because proteoglycans restrain it - large bottle brushed moving past brushes also provides frictions - slows it down
• The fluid is redistributed within the tissue away from the point of compression
• This redistribution is only slow, because the proteoglycans entrapped in the collagen meshwork impede the flow of fluid
• The bottlebrushes sliding past each other leads to a large frictional drag.
Therefore, cartilage only deforms gradually under load – “A DAMPING EFFECT”

32
Q

How can reversible compressibility be lost?

A

When LanthanumChloride is added - causes precipitation proteoglycans - SOKOLOFFs experiment - Cartilage 5

33
Q

What is Thomas experiment?

A

Cartilage 6 - Papain experiment - destroys cartilage so structural function is lost

TSM (67 decks)

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