Collagen Biochem and Matrix Disease Flashcards

1
Q

how much of the ECM makes up our body composition?

A

80%

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2
Q

what is the ECM?

A

cellular component of tissues

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3
Q

what does the ECM do?

A

-provides a scaffold for tissue development
-provides mechanical basis for cell attachment and movement
-transmits force
-withstand compression in cartilage and IVD
-provides survival signals to cells
-reservoir for growth factors

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4
Q

what makes up the ECM?

A

-water (50%)
-proteins
-glycoproteins
-proteoglycans
-GAG’s

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5
Q

what is the structure of collagen?

A

-30% of protein mass
-major component of connective tissue
-Gly-X-Y repeat
-triple helical structure
-tesnile forces

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6
Q

what do most common collagen disease mutate?

A

glycine

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7
Q

what is the function of facit collagen?

A

regulate fibril diameter, modify fibril interactions

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8
Q

what is the function of network forming collagen?

A

molecular sieves, planar support for cells

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9
Q

what is the function of transmembrane collagen?

A

cell matrix interactions, planar support for cells

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10
Q

what is the function of endostatin producing collagen?

A

produce regulators of cell migration and signalling

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11
Q

what is the function of anchoring fibril collagen?

A

cell matrix interactions

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12
Q

what is the function of bead forming collagen?

A

elasticity, long range connectivity

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13
Q

what is the structure of a collagen triple helix?

A

-3 poly peptide chains
-each chain Is a polypro line helix
-three chains fold into a triple helix
-each chain has a repeating glycine-X-Y residue triplet

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14
Q

what is the process of the collagen maturation?

A

-pro alpha chains come together in the ER
-proline residues get modified becoming hydroxylated
-this helps protein fold
-lysines are also hydroxylated, becoming a substrate for sugar molecules to attach to
-once triple helix is formed, amino acid no longer available and get secreted

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15
Q

what enzymes cleave the end C/N pro peptides?

A

C-proteinase
Bmp1 (tolloid family)
N-proteinase
ADAMTS family members
(a disinterring and metalloproteinase with thrombospondin repeats)

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16
Q

what is the half life of collagen?

A

120 years

17
Q

where is there collagen turnover?

A

some turnover on the peripheral edges of tendons ect but in the central core there is none

18
Q

how does type I OI present?

A

-less severe
-asymptomatic at birth
-early onset, few fractures
-null mutations, mutations that prevent or stop collagen being produced, not enough to make fibrils
-reduced collagen levels, no issues with quality

19
Q

what kind of mutations can cause mild OI?

A

stop codons - lead to premature stop codon, don’t have enough protein produced
promoter mutations - affecting amount of collagen being produced
mRNA instability - so it is degraded and not translated

20
Q

what is recessive OI?

A

-enzyme mutation stops collagen secretion
-prevents aggregation of collagen inside

21
Q

what are some more severe mutations that are present with OI?

A

-triple helix formation is stopped, continues becoming more modified which affects protein binding
-reduced quality
-therefor not only you have a mutant collagen, less collagen also

22
Q

what is FACIT collagen?

A

a type of collagen and also a proteoglycan that have two or more triple-helical domains that connect to collagen fibrils and share protein domains with non-collagen matrix molecules

23
Q

what is the structure of pro-collagen?

A

still unwound at the ends, ends need to be modified

24
Q

which amino acids mainly make up collagen?

A

-glycine found at almost every 3rd residue
-proline makes up about 17% of collagen

25
Q

what is the main type of collagen present in articular cartilage?

A

type 2

26
Q

what is the main type of collagen present in a normal tendon?

A

type 1

27
Q

what kind of cells are in a tendon?

A

tenoblasts
tenocytes
chondrocytes
synovial cells
vascular cells

28
Q

what are tenoblasts?

A

immature tendon cells, initially they are different in size and shape but as they age they become elongated and spindle shapes to form into tenocytes

29
Q

what are tenocytes?

A

mature tendoblasts, responsible for turnover and maintenance of the ECM. respond to mechanical load of the tendon and make adaptations.

30
Q

how are tenocytes arranged?

A

arranged in longitudinal rows and have extensive communication with adjacent cells usually via gap junctions

31
Q

what connects tendons to bone?

A

sharpey fibres