Extracellular Matrix & Connective Tissue Flashcards
The following describes the structure of what biomolecule found in the extracellular matrix:
found in synovial fluid of joints, arterial walls, bone and cartilage, and the ocular vitreous humor.
proteoglycans
Proteoglycans interact with proteins in the matrix such as collagen and elastin, fibronectin, and laminin. Collagen and elastin play ___ roles. Fibronectin is involved in cell ___ and ___.
structural; adhesion, migration
Proteoglycans consist of a ___ protein covalently attach to many long, linear chains of _____.
core; glycosaminoglycans
Glycosaminoglycans are made of repeating ____ units. These repeating units usually contain a ____ and an ___ acid. These sugars are frequently sulfated. Therefore they repel each other (due to negative charge) and act as a lubricant.
disaccharide; hexosamine, uronic
Proteoglycans occupy a very large space and act as “molecular ____”. These properties give some flexibility to substances such as cartilage, compression and re-expansion
sieves
There are at least seven types of glycosaminoglycans, which differ in the monosaccharides present in their repeating disaccharide units. Name all 7.
chondoritin sulfate dermatan sulfate heparan heparan sulfate hyaluronic acid keratan sulfate I keratan sulfate II
All glycosaminoglycans except ___ ___ are attached to proteins by covalent linkage to serine or threonine residues.
hyaluronic acid
Keratan sulfate I is attached via ____ residues
asparagine
Once the protein enters the ER, synthesis of the proteoglycans starts with the attachment of a ___ to serine or threonine residues of the protein
sugar
____-sugars are the substrates for proteoglycan synthesis
UDP
Specific UDP-sugar ________ are responsible for sequential transfer of monosaccharides from a nucleotide-linked sugar to an appropriate acceptor
glycosyltransferases
Sulfate groups are added through N- and O-sulfation, and they occur after the addition of sugars. What provides the sulfate groups for this reaction?
PAPS
3’ phosphoadenosine 5’
Once the synthesis of the proteoglycan is complete, it is secreted and forms the ___ ____
extracellular matrix
Proteoglycan ___ is formed by nonequivalent interaction between core protein and hyaluronic acid
aggregate
What is the function of hyaluronic acid?
cell migration, embryogenesis, morphogenesis, wound healing
What is the function of chondroitin sulfate?
formation of bone, cartilage, cornea
What is the function of keratan sulfate?
transparency of cornea
What is the function of dermatan sulfate?
transparency of cornea, binds LDL to plasma wall
What is the function of heparin?
anticoagulant, releases lipoprotein lipase from capillary walls
What is the function of heparan sulfate
component of skin fibroblast and aortic wall, commonly found on cell surfaces
The following describes the structure of what biomolecule:
usually contain shorter carbohydrate chain than proteoglycans, The carbohydrate moiety is often branched and is not made of repeating disaccharides. Most circulating proteins in the blood are this biomolecule
glycoproteins
In synthesis of glycoproteins, carbohydrate monomers are added to the protein in the lumen of ER and the golgi complex. In most cases, the initial sugar is added either through O-linkage to ___ or ___ residues, or N-linkage to an ___ residue.
serine; threonine; asparagine
In regards to O-linked glycosides, glycosylation of the protein begins with the attachment of an __________ onto a specific serial or threonyl side chain of the protein
N-acetyl-galactosamine
In regards to O-linked glycosides, glycoproteins that are destined to plasma membrane will be integrated to the Golgi membrane with glycosyl moiety facing the ___ lumen.
Golgi
In regards to O-linked glycosides, glycoproteins that are destined to be secreted from the cell remain ___ in the lumen. ___ vesicles bud off the Golgi and fuse with the cell membrane releasing the glycoproteins to the extracellular space
free; secondary
In regards to N-linked glycosides, the protein itself does not become glycosylated with individual sugars; instead a lipid-linked _______ is first constructed.
oligosaccharide
In regards to N-linked glycosides, after the oligosaccharide is constructed, the sugars are then added by the membrane-bound _______
glycosyltransferase
Oligosaccharides are transferred from the dolichol to asparagine residues of the protein by a ____-_____ transferase enzyme present in the ER
protein-oligosaccharide
Lysosomal enzymes degrade proteoglycans and glycoproteins bought into the cell by the process of ____
endocytosis
The carbohydrate moiety is degraded by the lysosomal ____
glycosidases
______ cleave carbohydrate chains to shorter oligosaccharides
_____, specific for each type of linkage, remove the sugar residue from the nonreducing end
endoglycosidases; exoglycosidases
All collagen types have a ____ ____ structure
triple helical
Each polypeptide subunit or alpha chain of collagen is twisted into a ___-handed helix of three residues per turn
left
Three alpha chains are then wound into a ___-handed superhelix. ____ bonding stabilizes this triple helix.
right; hydrogen
______ residues occur at every third position of the triple helical portion of the alpha chain
glycine
____ and ____ residues as X and Y in Gly-X-Y increase rigidity of the collagen
proline; hydroxyproline
Collagen is synthesized as a ____, which contains a signal sequence and polypeptide extensions
preprocollagen
In regard to collagen synthesis, extension peptides contain ___ residues
cysteine (disulfide bridges)
Hydroxyproline is formed post-transcriptionally by hydroxylation of the proline residues by a ___ ___ enzyme. The enzyme requires ascorbic acid and alpha ketoglutarate as cofactors
prolyl hydroxylase
Lysine and hydroxylysine can participate in the __ position in Gly-X-Y
Y
Several collagen types do not form fibrils in tissues. They are characterized as “____” of the triple helix with stretches of protein lacking Gly-X-Y repeat structures
interruptions
Collagen ___ is the best known example of collagens with discontinuous triple helices
IV
Where is Type I collagen found?
skin, bone, tendon, blood vessels, cornea
Where is type II collagen found?
cartilage, intervertebral disk, nitrous body
Where is type III collagen found?
blood vessels, fetal skin
Where is type IV collagen found?
basement membrane
Where is type V collagen found?
same as type I
This syndrome comprises a group of inherited disorders whose principal clinical features are hyper extensibility of the skin, abnormal tissue fragility, and increased joint mobility.
Ehlers-Danlos syndrom
Type ___ Ehlers-Danlos syndrome is the most serious because of its tendency for spontaneous rupture of arteries of the bowel, reflecting abnormalities in collagen III.
IV
Type ____ Ehlers-Danlos syndrome is due to lysl hyroxylase deficiency. Patients exhibit marked joint hyper mobility and tendency to ocular rupture
VI
Type ___ Ehlers-Danlos syndrome is due to procollagen N-proteinase deficiency, causing formation of abnormal thin, irregular collagen fibrils, manifested by marked joint hyper mobility.
VIIC
This syndrome is referred to a group of genetic abnormalities affecting the structure of type IV collagen fibers. Patients are represented with hematuria and may eventually develop end-stage renal disease due to basal membrane abnormalities.
alport syndrom
Scurvy affects the structure of collagen due to a deficiency in what vitamin?
vitamin C
What are the major signs of scurvy?
bleeding gums, subcutaneous hemorrhages, and poor wound healing (due to deficiency of prolyl and lysyl hydroxylase activity)
___ is a connective tissue that is responsible for properties of extensibility and elastic recoil in tissue
elastin
Elastin is synthesized in a single ___ molecule.
tropoelastin
True or false?
elastin does not have extension peptides, Gly-X-Y arrangement, triple helical structure, or carbohydrate moiety
true
____ are the major cross-links of elastin
desmosines
Deletions in elastin gene have been found in 90% of subjects with ___ syndrome, a developmental disorder affecting connective tissue and the CNS
williams
Mutations effecting the synthesis of elastin probably play a causative role in the supravalvular ___ ____ often found in this condition
aortic stenosis
Fibrillin is a large glycoprotein found in many tissues. It is secreted into the extracellular matrix by ____
fibroblasts
This is an autosomal dominant disease affecting connective tissue. Most patients exhibit long digits and hyperextensibility of the joints, and cardiovascular problems
marfan syndrom
Marfan syndrome is due to a mutation in the ___ gene
fibrillin
This is a soluble glycoprotein found in large amounts in the extracellular matrix. It is a dimer, joined by disulfide bonds near their terminal
fibronectin
Fibronectin receptor belongs to a family of transmembrane ___ class of proteins
integrin
Fibronectin contains Arg-Gly-Asp sequence that binds to integrin. True or false?
true
This consists of a3 distinct elongated polypeptide chains linked to together to form an elongated cruciform shape. It has a binding site for type IV collagen, heparan, and integrin on the cell surface
laminin
What are the three primary components of the basal lamina?
laminin, entactin, and type IV collagen
