Biochem Lecture 3 Flashcards
(58 cards)
1
Q
How much collagen is found in the human body?
A
1/4 of all protein is collagen
2
Q
How much collagen is found in skin?
A
74%
3
Q
How much collagen is glycine residue?
A
33%
4
Q
How long is collagen?
A
1000 AA long
3000 A long / 300 nm
15 A thick
5
Q
Collagen triple helix
A
- glycine groups face inward
- LEFT hand alpha helix but RIGHT hand triple helix
6
Q
True or False
Collagen contains glycine groups that face outward
A
FALSE
- glycine groups face inward
7
Q
Fibrous Proteins
A
- Contain larger amounts of regular secondary structure
- Long cylindrical
- Low solubility in water
- Structural role
8
Q
True or False
Fibrous Proteins have low solubility in water
A
TRUE
9
Q
Collagen, keratin, and tropomyosin
A
Examples of Fibrous Protein
10
Q
Globular Proteins
A
- Less secondary structures
- High solubility in water
- Dynamic role; meaning gives function to enzymes
11
Q
True or False
Globular Proteins have a dynamic role
A
TRUE
12
Q
True or False
Globular Proteins have a low solubility in water
A
FALSE
Globular Protein s have a High solubility in water
13
Q
What is the most plentiful protein in the human body?
A
Collagen
14
Q
Collagen
A
- MAJOR insoluble fibrous protein
- Gives tissues their strength
- located in all tissues and organs
15
Q
Where is collagen located?
A
Extracellular matrix and connective tissue
16
Q
Collagen Type 1
A
Skin, tendon, bone, ligaments, dentin, interstitial tissues
17
Q
Collagen Type 2 and 9
A
Cartilage and Vitreous humor
Linked together ultimately make the structure of cartilage
18
Q
Collagen Type 3
A
Skin, muscle, blood vessels
19
Q
Collagen Type 5
A
Similar to type 1 but including cell cultures and fetal tissue
20
Q
Collagen Type 4
A
- Basal lamina
- 2D
- Mesh like network to connect things form scaffolds
21
Q
Alpha Helix of Collagen
A
- cross linked by disulfide bonds
- L hand turn
22
Q
Beta Conformation
A
Silk Fibrion
23
Q
Collagen basic unit of structure is
A
Triple Helix
24
Q
Triple helix
A
- High Tensile strength, without stretch
- Repeating Tripeptide sequence
- Each strand is H bonded to the other two strands
25
True or False
| Proline R groups are on the outside
TRUE
26
True or False
| Steric Hindrance does not allow for stretching and elongation of strand which leads to tight twisting
FALSE
Steric Hindrance allows for stretching and elongation of strand
27
Does Triple helix have a right or left handed turn?
Right
(after all three chains have combined)
The collagen triple helix is made of three collagen peptides, each of which forms its own left-handed polyproline helix
When the three chains combine, the triple helix adopts a right-handed orientation
Normally alpha helix is right handed
28
Glycine is always in the ______ position
Third
Due to SMALL side chain, can fit in the middle and is required at the tight junction where the three chains are in contact
29
How many residues per turn?
3
Remember the difference - Alpha helix has 3.6 per a turn
Ex: Collagen of tendon, bone matrix
30
Gly-X-Y, Gly-X-Pro, or Gly-X-HPro
Repeating Tripeptide Sequence
31
Proline
- Steric Hindrance allows for stretching and elongation of strand which leads to tight twisting
- Proline R groups are on the outside
- Each strand is H-bonded to the other two strands
32
Hydroxylated Amino Acids in Collagen
4-Hydroxyproline
- Formation is done by a Pro + Alpha Ketoglutarate and O2 with enzyme prolyl hydroxylase and Ascorbate which results in a 4-Hydroxy Prolyl residue and succinate
NEEDS ascorbate in formation of hydroxyproline
Adds stability
33
What enzymes are used in 4-Hydroxyproline formation?
Prolyl Hydroxylase
and
Ascorbate
34
Name the Hydroxylated Amino Acids in Collagen
4-Hydroxyproline
3-hydroxyproline
5-hydroxylysine
35
5-hydroxylysine
Alpha Chains of Collagen and Collagen Fibrils are CROSSLINKED by unusual types of covalent bonds involving lys, hylys, or His.
36
Collagen Glycosylation
Addition of Galactose and Glucose to only hydroxylysine
37
What will the addition of Galactose and Glucose do to the collagen triple helix?
- Stabilizes the triple helix of collagen
Once triple helix forms, glycosylation ceases
38
Biosynthesis of Type 1 collagen
- DNA to mRNA to ribosome forms the single alpha helix as soon as it leaves the ribosome.
- Alpha helix is hydroxylated on the prolines and lysines
- Glycosylation of the Hydroxylysine
- Triple helix formation is in the ER and Golgi. Three alpha helices being put together C to N terminus winding together
- Once Outside the Cell the Pro collagen molecule will get cleaved to make a mature collagen molecules
- Mature collagen gets assembled into fibrils
- Fibrils are held together partially by the covalent linking between lysine and hydroxylysine, histidine
- Fibrils come together to make a fiber.
39
Enzymes in biosynthesis
Enzyme prolyl hydroxylase and, O2, Ascorbate (Vitamin C)
40
Glycosylation of the Hydroxylysine
Galactose and Glucose
41
Intramolecular and Intermolecular cross linking can be between
lysine
histidine
& hydroxylysine
42
Intramolecular
within one chain
43
Intermolecular
- Between different chains and important in the formation of a fibril
- They overlap by ¼ staggered fashion→ makes striations.
44
Covalent Cross Linking of Collagen
- Strengthens fiber
| - Hydroxylysine that has been glycosylated can still participate in crosslinking
45
Covalent Cross Linking of Collagen occurs by:
- Lysl oxidase reaction creates an aldehyde which can reacts with a lysine to form a schiff base
- and ultimately a cross link in collagen or another way is when two aldehydes react together in an aldol condensation and form an aldehyde cross link
46
Associate diseases with collagen synthesis
Abnormal collagen genes, abnormal postranslational modification of collagen or deficiency of cofactors needed by enzymes responsible for translational modification of collagen
47
Diseases of Collagen
OSteogenesis
Ehlers-Danlos Syndrome
Scurvy
48
Diseases of Collagen
```
OSteogenesis
Ehlers-Danlos Syndrome
Scurvy
Tissue collagenases
Bacterial collagenase
Fibril
```
49
Ehlers-Danlos Syndrome
- Joint hypermobility
- Easily bruised
- Stretchable skin
50
Scurvy
- Liver spots on skin
- Spngy gums→ leads to tooth loss
- Fingernail decay
Due to lack of HYDROXYLATION of LYS and PRO in collagen
- Vitamin C deficiency so lack of collagen production
(Ascorbate = vitamin C)
51
Tissue collagenases
Enzymes that break down collagen, sometimes used to heal a wound but most times used by tumors so the tumors can secrete and break down basement membranes so tumors can invade deeper and ultimately into blood vessels.
52
Bacterial collagenase
Clostidrium collagenase
- Toxin O is a type of collagenase secreted by clostridium that is involved in gas greene.
- COPD is associated with collagenases due to breakdown of alveoli in lung and cancer metastasis.
53
Fibril
Triple helices together to form a fiber
- Triple helix held by
H bonding of glycine resides and can have covalent bonding in it.
- Fibril Held together by covalent bonds
54
What is the most abundant Amino acid that is required every 3rd position in the collagen sequence?
Glycine
55
What results from a constant pattern in collagen?
Straistions
56
Cross-links involved in the reaction of lysine residues go through reaction and are stabilized with what?
lysyl amino oxidase
Remember- Crosslinks are present in collagen
57
Hydroxylation of proline requires what do that it can take place?
Prolyl hydroxylase and theascorbate
58
What is used important for the turnover of collagen?
collagenases
