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Biochemistry > Composition and structure of connective tissue > Flashcards

Composition and structure of connective tissue Flashcards

1
Q

Give 3 examples of functions of connective tissue?

A

Mechanical support

Assist movement

Site of immune response

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2
Q

Do connective tissues contain neurovascular structures?

A

Yes

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3
Q

What are the 3 main components of connective tissue?

A

Cells

Structural components (in ECM)

Matricellular proteins (in ECM)

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4
Q

What is the function of cells in connective tissue, and give 3 examples of body structures that contain connective tissue and the associated cells?

A

Cells synthesise and breakdown connective tissue

Fibroblasts in skin and tendon ligaments

Chondrocytes in cartilage

Osteocytes, osteoblasts, osteoclasts in bone

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5
Q

What is the main function of structural components in connective tissue?

A

Provide mechanical properties by providing ground substance

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6
Q

What is ground substance, that composes structural components of connective tissue?

A

Amorphous/shapeless gelatinous material that contains all ECM components except from fibrous materials

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7
Q

What 3 substances make up the ground substance in the structural components of connective tissue?

A

proteoglycan predominantly, elastic and collagen fibres

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8
Q

Describe the structure of a proteoglycan?

A

Protein core coated by sugar-based polymers called glycosaminoglycans/GAGs/glycans

Different kinds of glycans which are built from different building blocks

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9
Q

Give 4 examples of properties of proteoglycans?

A

size variation ranges from 40dKa to over 100dKa

hydrophilic so allow water to be held in tissues

viscoelastic

interaction with cells, collagen and cytokines

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10
Q

What is aggrecan, and how does it form aggregate?

A

Aggrecans are proteoglycans that cluster with hyaluronan and link proteins to form a huge multimeric (protein composed of subunits) aggregate

Aggregate is a ball-shaped structures that give cartilage resistance to compression in cartilage

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11
Q

What is the function of link proteins in aggregate?

A

Link proteins stabilise binding of aggrecans to hyaluronan backbone

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12
Q

What structure coating aggregate makes it hydrophilic, and what property does this give the connective tissue overall?

A

Hydrophilic sulfated chondroitin-keratin sulphate complex chains of aggregates draw water into tissue which allows resistance to compression

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13
Q

In OA, how are aggregates and type 2 collagen fibres affected?

A

In OA, aggrecan and type II collagen are degraded by proteolytic enzymes which impairs mechanical properties of cartilage, causing joint pain

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14
Q

Do matricellular proteins have regulatory or structural roles?

A

Regulatory

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15
Q

In elastic fibres, what is the diameter of the microfibrils that compose them?

A

10nm

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16
Q

What 4 body structures contain elastic fibres so that they can stretch?

A

blood vessel walls, alveoli, bladder, tendons

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17
Q

What do elastic fibres target and activate?

A

Growth factors, especially TGF-beta

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18
Q

What 4 proteins compose elastic fibres?

A

elastin

fibrillin 1,2,3 proteins

fibulin 4,5 proteins

matrix-associated glycoproteins

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19
Q

Describe the composition and arrangement of elastic fibres in tendons?

A

In tendons, elastic fibres composed by long microfibrils and sit between collagen fibre bundles

20
Q

What is the main matricellular protein and structural component of connective tissue?

A

Type 1,2,3 collagen fibres

21
Q

How many types of collagen are there, and how many genes are these expressed by?

A

27 collagens that are expressed by 42 genes

22
Q

What is each collagen molecule in a collagen fibril composed of, and how many genes are expressed to produce these?

A

Collagen fibrils are composed of many collagen molecules, with each molecule consisting of triple helix alpha polypeptide chains

each chain is a single gene product

23
Q

What is the amino acid sequence of an alpha polypeptide chain which makes up collagen fibrils?

A

Glycine-X-Y repeats, where X is usually proline and Y is usually hydroxyproline (unusual AA that is mostly found in collagen)

24
Q

What part of the amino acid sequence of alpha polypeptide chains allows them to intertwine and form a triple helix alpha polypeptide molecule?

A

Glycine is every 3rd residue in the amino acid sequence

25
Q

What 2 properties do proline and hydroxyproline give collagen?

A

Rigidity, stability

26
Q

Describe the turnover rate of collagen fibres?

A

Very slow turnover rate, so collagen is very stable

27
Q

What percentage of the whole-body protein content is made up by collagen fibres?

A

12-17%

28
Q

What is a homotrimer collagen and give one example?

A

Protein composed of 3 identical alpha polypeptide chains

eg. Type 2 collagen

29
Q

What is a heterotrimer collagen and give one example

A

Protein composed of 2 or more different alpha polypeptide chains

eg. Type 1 collagen in skin and bone has 2 identical alpha chains and 1 different alpha chain

30
Q

In collagen fibril synthesis, what occurs after alpha polypeptide chain translation?

A

Post-translational modification at RER of alpha polypeptide chain:

proline and lysine hydroxylation (vitamin C/ascorbate is cofactor)

hydroxylysine glycosylation

31
Q

In collagen fibril synthesis, after the 3 alpha polypeptide chains have been modified how do they assemble into the triple helix alpha polypeptide molecules, and what is the name of this molecule?

A

3 modified alpha polypeptide chains form disulfide bonds between them to intertwine tightly and produce triple helix alpha polypeptide molecule which is called procollagen

32
Q

In collagen synthesis, what happens to procollagen after it is produced in the cell?

A

Procollagen secreted from cell by exocytosis and enters ECM

33
Q

In collagen fibril synthesis, how is procollagen converted into tropocollagen?

A

In ECM, N and C proteinases cleave N and C propeptides from procollagen, converting it to tropocollagen

34
Q

In collagen fibril synthesis, how do tropocollagen molecules from a collagen fibril, and what enzyme catalyses this step?

A

Tropocollagen molecules assemble into collagen fibrils, then lysyl oxidase forms covalent cross-linkages between the molecules

35
Q

How can vitamin C deficiency affect the strength of collagen fibrils, and what is the resulting condition?

A

Vitamin C deficiency reduces hydroxylation of proline and lysine, which weakens triple helix structure of procollagen, overall weaker collagen fibrils are formed and this presents as scurvy

36
Q

Give 5 symptoms of scurvy?

A

Gum bleeding, teeth loss, skin lesions and bruising, joint pain and weakness, poor wound healing

37
Q

Do all connective tissues have the same composition and organisation of collagen?

A

Different types of connective tissues have varying compositions and organisations of collagen

38
Q

What is the primary protein component in bone, and how is it organised?

A

Primary protein component is type 1 collagen fibres which are arranged into concentric circular structures called lamellae

39
Q

In tendons, how does collagen provide high tensile strength?

A

Parallel type 1 collagen fibre bundles provide tensile strength

40
Q

In enthesis, do the proportions of collagen remain constant throughout its length?

A

No, enthesis structure varies along it length due to different collagen proportions

41
Q

Why is the enthesis a common site of tendon pathology, and give 2 examples?

A

Mechanical stress is concentrated here, so microdamage and overuse injuries often occur

42
Q

Give 5 examples of tendinopathy changes to collagen proportions and organisation?

A

Disorganised collagen fibrils

reduced fibril diameter

increased collagen turnover leads to higher proportion of type 3 collagen fibres

neurovascular infiltration which causes pain

failure to repair

43
Q

In skin and blood vessels, what type of collagen forms the collagen fibrils?

A

Mixed fibrils formed from type 1,3 collagen

44
Q

What kind of deficiencies can cause conditions with fragile skin and blood vessels?

A

Fragility occurs due to impaired collagen fibril formation from deficiencies in type 3 collagen (expressed by COL3A1 gene) which can lead to conditions such as Ehlers Danlos syndrome type IV

45
Q

What percentages of types 1 and 3 collagen make up skin and blood vessels?

A

~60% type 1 collagen

~30% type 3 collagen

Biochemistry (7 decks)

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