Biochemistry Flashcards
1
Q
Where are proteoglycans found?
A
- Synovial fluid of joints
- Arterial Walls
- Bone
- Cartilage
- Ocular Vitreous Humor
2
Q
Proteoglycans act as “molecular sieves.” What does this mean?
A
They control which substances approach and leave the cell
3
Q
What are proteoglycans composed of?
A
- A core protein covalently attached to many long linear chains of glycosaminoglycans
4
Q
What are glycosaminoglycans (GAGs) composed of?
A
- Repeating disaccharide units each usually containing hexosamine and an uronic acid
- Frequently sulfated
- Highly negative
- Highly hydrated
- Act as a lubricant
5
Q
Draw the basic structure of proteoglycans.
A
6
Q
What are the seven different types of glycosaminoglycans?
A
- Chondroitin sulfate
- Dermatan sulfate
- Heparin
- Heparin sulfate
- Hyaluronic acid
- Keratin sulfate I
- Keratin Sulfate II
7
Q
Hyaluronic acid associates with proteins through what linkage?
A
Noncovalent
8
Q
All GAGs, except hyaluronic acid, are attached to proteins via what kind of linkage and to what residues?
A
Covalent linkage to serine or threonine residues
Keratan sulfate I is attached via asparagine
All are Polar, Uncharged Residues
9
Q
Describe synthesis of proteoglycans.
A
- Protein enters ER, sugars are attached to serine or threonine residues of the protein
- Linking sugars Xylose, Galactose, Galactose are attached
- UDP-sugars are the substrates for synthesis. UDP-sugar glycosyltransferases sequentially transfer monosaccharides from a nucleotide-linked sugar to an appropriate acceptor
- Alternatively add repeating monosaccharide units to the groing GAG
- After addition of sugars, sulfate groups are added through N- and O-sulfation
- 3’ phosphoadenosine 5’ -phosphosulfate (PAPS) provides sulfate groups for reaction
- Complete proteoglycan is secreted and forms ECM
10
Q
What differs glycoproteins from proteoglycans?
A
- Glycoproteins usually ahve shorter carbohydrate chains
- These are often branched and not made of repeatind disaccharides
11
Q
Describe synthesis of glycoproteins.
A
Carbohydrated monomers are added to protein in lumen of ER and Golgi
In most cases:
- Initial sugar is added either through O-linkage (serine or threonine residues) or through N-linkage (asparagines). Side chain is extended by sequential addition of sugar residues to nonreducing end
- O-linkage
- Glycosylation begins with attachement of an N-acetyl-galactosamine onto a specific seryl or threonyl side chain of protein
- Glycoproteins destined for plasma membrane integrate to Golgi membrane w/ glycosyl moiety facing Golgi lumen
- Glycoproteins destined to be secreted remain free in the lumen and are secreted via secondary vesicles
- N-linkage
- Construction of lipid linked oligosaccharide. A membrane bound dolichol molecule (lipid) attached through a pyrophosphate linkage to an oligosaccharide containing N-acetylglucosamine, mannos, and glucose
- Membrane bound glycosyltransferases add sugars to the dolichol
- Oligosaccharides are transferred from dolichol to asparagine residues by protein-oligosaccharide transferase
- O-linkage
12
Q
How are proteoglycans and glycoproteins degraded?
A
- They are brought into cells via endocytosis and degraded by lysosomal enzymes
- Glycosidases degrade the carbohydrate moiety
- Endoglycosidases cleave carbohydrated chains to shorter oligosaccharides
- Exoglycosidases are specific for each type of linkage and remove the sugar residue from the nonreducing end
13
Q
How is collagen structured?
A
- Triple helical structure
- Each polypeptide subunit (alpha chain) is twisted into L-handed helix (three residues per turn)
- Glycine residues occur at every third position of alpha chain
- Repeating structure of (Gly-X-Y)
- About 100 of X and Y are proline or hydroxyproline (increase rigidity)
- Three alpha chains are then wound into R-handed superhelix
- Creates rod like structure 1.4 nm in diameter about 300 nm long
- Hydrogen bonds stabilize the triple helix structure
- Each polypeptide subunit (alpha chain) is twisted into L-handed helix (three residues per turn)
14
Q
How is collagen synthesized and assembled?
A
- Synthesized as preprocollagen
- Contains signal sequence removed in the ER
- 25-30 kDa pro-polypeptide extensions at N and C terminals
- Contain cysteine residues
- N-terminal - interchain disulfide bonds
- C-terminal - inter and intrachain disulfide bonds
- Assists in registration of the three collagen molecules to form triple helix
- Helix is wound form carboxyl terminal
- Contain cysteine residues
- Assmebly of collagen
- Hydroxyproline formed posttranscriptionally by a prolyl hydroxylase
- Enzyme requires Vitamin C and alpha-ketoglutarate
- Lysine and hydroxylysine can participate in Y position of (Gly-X-Y) lysine is hydroxylated post-transcriptionally by lysyl hydroxylase
- Has similar co-factors
- Selected Hydroxylysines are glycosylated
- Procollagen triple-helix is secreted
- Propeptides are cleaved
- Collagen molecules self assemble into fibrils
- Hydroxyproline formed posttranscriptionally by a prolyl hydroxylase
- Several types of collagen do not form fibrils in tissue because of “interruptions” of the triple helix with stretches of protein lacking Gly-X-Y sequence
- Type IV collagen is best-known example
15
Q
The major cross-links of elastin?
A
Desmosines
- Three lysine derived aldehydes link with an unmodified lysine to form this cross-link
- Elastin become highly insoluble and highly stable
