Term
| Where is type I collagen found? |
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Definition
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Term
| Where is type II collagen found? |
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Definition
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Term
| Where is type III collagen found? |
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Definition
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Term
| Where is type IV collagen found? |
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Definition
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Term
| where is type V collagen found? |
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Definition
| fetal membranes associated with type I |
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Term
| What is unique about type IV collagen with respect to the other 4 major types? |
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Definition
| It is a network forming collagen while the other four major types are all fibrillar |
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Term
| What is the primary structure of collagen? |
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Definition
-Gly-X-Y-Gly-X-Y-Gly-X-Y-Gly-X-Y-Gly-X-Y
Glycine every 3 residues |
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Term
| What is the secondary structure of collagen? |
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Definition
an alpha chain which is DIFFERENT from an alpha helix
left-handed polyproline type II helix.
Tightly twisted with 3 residues per turn and the peptide bonds perpendicular to the axis (in
contrast to the a-helix where peptide bonds are parallel to the helical axis).
Helix forms because of the properties of pro and hyp, units of which occur at about every fourth
position in collagen.
Helix is stabilized by the solvation properties of hyp and pro, and by strong interchain hydrogen
bonding (collagen consists of three chains) |
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Term
| What is the tertiary structure of collagen? |
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Definition
Individual alpha chains are stabilized and shaped by the steric repulsions of the bulky proline and hydroxyproline side chains
twisted right-handed superhelix |
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Term
| What is the quaternary structure of collagen? |
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Definition
Three alpha chains wrap around each other to form a triple helix. The smallness of glycine allows the close contact between the alpha chains.
The superhelical (triple helix) units of collagen are aligned head to tail in a staggered array,
forming a collagen microfibril (still quartenary structure). |
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Term
| How does imino acid content relate to Tm, Ts and body tempature? How is it important? |
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Definition
Imino acid content is the percentage of proline and hydroxyproline
The higher the percentage of pro and hyp the higher the Tm (melting temperature) and Ts (shrinkage temperature) of collagen.
This is important because the Tm has to be above body temperature or collagen will not remain correctly formed |
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Term
| How does the amino acid composition of elastin differ from that of collagen? |
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Definition
Although total glycine percentage is the same, glycine does not occur every 3 residues.
Not as much proline or hydroxyproline
No hydroxylysine
high amount of non-polar amino acids - (ala, val, leu, ile more than 80%) |
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Term
| What are the crosslinks present in elastin? |
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Definition
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Term
| What are the crosslinks present in collagen? |
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Definition
Lysinonorleucine
aldol condensation crosslinks |
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Term
| How are the aldol condensation crosslinks formed? |
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Definition
| The amino group on the lysyl residues is changed to an aldehyde group by lysyl amino oxidase and then the aldehyde groups on two separate peptides undergo aldol condensation and form a crosslink. |
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Term
| What is the role of copper in cross-linking? |
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Definition
| The enzyme lysyl amino oxidase is copper-containing so it requires copper to function. Copper deficiency or copper chelation will negatively affect lysyl amino oxidase. |
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Term
| What is the role of ascorbic acid in cross-linking? |
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Definition
Ascorbic acid (better known as Vit C) is a required co-factor in the reaction of
prolyl (or lysyl) residue with alpha-ketoglutarate to form hdroxyprolyl (or hydroxylysyl).
Hydroxylation is important for the formation of the triple helix of collagen and are necessary for
glycosylation.
Procollagen that is not properly hydroxylated is slowly secreted and rapidly degraded.
Thus the cross-links will not be formed w/o Vit C |
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Term
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Definition
Lathyrism is a dietary disease that arises from regular consumption of seeds of Lathyrus odoratus, the sweet pea.
The seeds contain ß-aminoproprionitrile which inactivates lysyl amino oxidase resulting in decreased crosslinking of collagen. Without these crosslinks, collagen is extremely fragile. |
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Term
| What is osteogenesis imperfecta? |
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Definition
| A collagen disorder - decrease in type I collagen |
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Term
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Definition
| A group of collagen disorders - some causes are decrease in type III, decreased cross-linking, decreased hydroxylysine, etc. |
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Term
| What is Menkes and how is it caused? |
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Definition
| It is a collagen disorder where there is decreased cross-linking. It is caused by copper malabsorption. Without enough copper lysyl amino oxidase can't operate effectively which leads to defective cross-linking. |
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Term
| What is homocysteinuria and how is it caused? |
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Definition
It is a collagen defect where there is abnormal cross-linking.
This is caused by a genetic defect in cystathionine synthetase.
The increased amounts of free homocysteine which have -SH groups that will interfere with the aldol condensation cross-links by reacting with the aldehyde groups |
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Term
| How does emphysema relate to elastase? |
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Definition
Elastase is a serine protease that hydrolyzes elastin and some other proteins (but NOT collagen)
Elastase is kept in check by alpha1 antitrypsin (the predominant one) and alpha2 macroglobulin.
In emphysema there is an imbalance between alpha1 antitrypsin and elastase.
Decreased alpha1 antitrypsin leads to increased elastase activity which will degrade more elastin in the lung tissue.
Related to smoking because smoking decreases alpha1 antitrypsin |
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Term
| What are the intracellular steps in collagen synthesis? |
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Definition
1) synthesis of the pro-alpha chain
2)hydroxylation of select lysines and prolines
3)glycosylation of select hydroxylysines
4) self assembly of three pro-alpha chains
5) procollagen triple helix formation
6) secretion to outside of the cell |
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Term
| What are the extracellular steps in collagen synthesis? |
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Definition
1) Procollagen peptidase cleaves off the registration peptides
2) self-assembly into fibril
3) cross-linking occurs and stabilizes fibril
4) collagen fibrils aggregate to form a collagen fiber |
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Term
| What is the structure and function of fibronectin? |
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Definition
It is a glycoprotein so it is a core protein with attached sugars.
Fibronectin is an elongated protein containing a linear array of domains. Each domain will bind certain molecules and functions in the following:
* The binding and release of collagen
* The binding of fibrin
* Cell binding (through the binding and release of integrin, a transmembrane protein)
* The binding of proteoglycans in the extracellular matrix (e.g. heparin sulfate) |
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Term
| What is the structure and function of laminin? |
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Definition
Laminin bind to a “laminin receptor” which include both integrin and non-integrin reeptors.
Entactin is a major cell attachment factor which bind to laminin
Laminin induces a number of physiological changes in cells, e.g., proliferation, migration,
differentiation and cell spreading. |
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Term
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Definition
| Glycosaminoglycans are long chain polysaccharides composed of repeating disaccharide units |
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Term
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Definition
| Polyanionic complex that consists of glycosaminoglycans covalently attached to a core protein |
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Term
| What is the structure of Hyaluronan |
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Definition
Glucuronic Acid + N-acetlyglucosamine
GlcUA-GlcNAc |
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Term
| What is the structure of keratan sulfate? |
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Definition
GlcNAc (Sulfated)-Gal
N-Acetylglucosamine - Galactose |
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Term
| What is the structure of dermatan sulfate? |
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Definition
Glucuronic acid/Iduronic acid - N-acetylgalactosamine
GlcUA/IdUA (Sulfated)-GalNAc (Sulfated |
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Term
| What is the structure of chondroitin sulfate? |
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Definition
GlcUA-GalNAc (Sulfated)
glucucornic acid - N-acetylgalactosamine |
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Term
What is the structure of heparin?
How is heparan sulfate related? |
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Definition
GlcUA/IdUA (Sulfated)-GlcNAc (N-Sulfate)
Glucuronic acid/iduronic acid - N-acetylglucosamine
Heparan sulfate has the same general structure but fewer sulfate residues |
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Term
| What are the functions of proteoglycans? |
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Definition
* Lubrication and fluid balance
* Supportive element in connective tissues
* Antithrombic (dermatan sulfate and heparan)
* Blood lipid clearing |
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Term
| What is Hurler's syndrome? |
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Definition
It is a mucopolysaccharidosis (disease of GAG metabolism)
affected enzyme is a-L-iduronidase
affected GAGs are dermatan sulfate and heparan sulfate |
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Term
| What is Hunter's syndrome? |
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Definition
IMPORTANT
It is a mucopolysaccharidosis (disease of GAG metabolism)
the enzyme defect is L-iduronate-2-sulfatase
affected GAG's are dermatan sulfate and heparan sulfate
the only X-linked MPS, there are mild and severe forms |
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Term
| What is Sanfillippo A syndrome? |
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Definition
It is a mucopolysaccharidosis (disease of GAG metabolism)
enzyme defect in heparan N-sulfatase
affects heparan sulfate |
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Term
| Why are the aldol cross-link reactions susceptible? |
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Definition
| The aldol condensation is a non enzymatic reaction and the aldehyde groups are reactive (ex - the -SH groups on homocysteine can react with them) |
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