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Definition
Fibrillar- Tendon, Skin, Ligament, tendon and bone 2 distinct chains |
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Definition
Fibrillar- Cartilage, vitrous humor 3 Identical Chains |
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Definition
Fibrillar- Skin, blood Vessels, Tendon, lung, and fresh scars 3 Identical Chains |
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Definition
Network Forming- Basement Membrane 2 Distinct Chains |
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Definition
Fibrillar- Fetal membranes, associated w/ type I 3 Distinct Chains |
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Definition
The main protein of connective tissue and the most abundant protein, making up about 40% of the total. May be insoluble or may not (soluble) be crosslinked. |
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Term
Tropocollagen/Triple Helix |
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Definition
The basic structural unit of collagen, consisting of three polypeptide chains. The tertiary arrangement of three polypeptide chains forming the basic unit of collagen fibers. |
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Term
| Collagen- Secondary Structure |
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Definition
A 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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| Collagen- Tertiary Structure |
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Definition
-Gly forms a nonpolar or apolar edge (why?). This along with the small size of Gly side chain allows the three collagen strands to come close together (quartenary structure). - Each polypeptide chain will assume a twisted right-handed superhelix (this is the tertiary - 3/ structure of each collagen chain) which has one turn to 10 turns of the secondary helix. - The supercoil structure is stabilized by hydrophobic interaction and inter chain hydrogen bonding. These collagens have a size of 15 x 3000 Angstroms and a molecular weight of 300,000. |
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Term
| Collagen-Quartenary Structure |
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Definition
- Starts with the three polypeptide chains forming the triple helix of collagen. - The superhelical (triple helix) units of collagen are aligned head to tail in a staggered array, fonning a collagen microfibril (still quartenary structure). |
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Term
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Definition
| The temperature at which half the helical structure is lost is called the melting temperature (Tm) of collagen. This temperature is indicative of the stability of the helical structure of collagen. |
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Definition
| shrinkage temperature (Ts). This is the point at which the collagen fiber is reduced to half its original size. |
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Term
| The dependence of Ts and Tm on Proline and Hydroxyproline Content |
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Definition
| The greater the body temperature of a species, the greater the imino acid content of that species collagen and the greater its Ts and Tm will be. |
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Term
| Collagen vs. Elastin AA's |
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Definition
| Elastin - Elastin, like collagen, is about 33% gly but contain a high amount of nonpolar amino acids (ala, val, leu, ile) and lower pro. Together these amino acids account for greater than 80% of the total amino acids. -There is a low amount of hyp and no hyl. - Gly does not occur every third amino acid as in collagen; it does occur in these sequences: Val-Pro-Gly-Val-Gly or Pro-Gly-Val-Gly-Val-Ala. |
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Term
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Definition
- The extracellular enzyme lysyl oxidase acts on tropoelastin to crosslink up to four different polypeptide chains. - This crosslink is called desmosine (see Fig. 13.8 in MB. p. 266). - Currently, it is thought that two polypeptide chains are joined by using a pair of lys residues from each. - Crosslinks are formed in several regions rich in lys and ala which occurs in sequences of Gly- Ala-Ala-Lys and Gly-Ala-Ala-Ala-Lys. |
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Term
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Definition
genetic defect in cystathionine synthetase, resulting in abnormal collagen crosslinking dislocation of the lens; a tall, thin build with long limbs; spidery fingers high arches of the feet, knock-knees and a curved spine. |
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Definition
decreased crosslinking due to copper malabsorption severe developmental delay, failure to thrive, kinky hair, abnormal arteries which can rupture, weakened bones (osteoporosis) that may fracture |
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Definition
Abnormal crosslinking due to inhibition of lysyl oxidase deformation of the spine, dislocation of joints and demineralization of bones |
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Term
Collagen Synthesis- Intracellular Events |
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Definition
- Each polypeptide chain of a collagen unit contains about 1000 an residues Synthesized as a preproprotein having a pre- or signal sequence at the amino terminus, an additional 180 aa at the amino terminal end and 300 aa at the carboxy terminal end. - The carboxy terminal propeptide plays a role in the formation of the collagen triple helix. - The signal sequence directs the movement of procollagen (also known as procollagen) into the rough endoplasmic reticulum. - Once the chains are inside the ER membrane the signal peptide is removed by a signal peptidase, also known as procolagen peptidase. - The protropocolagen transcripts are modified as they are being synthesized by hydroxylation and glycosylation. - Hydroxylation is important for the formadon of die triple helix of collagen and are necessary for glycosylation. Pro and lys are hydroxylated, after they are incorporated into the collagen polypeptide chain, by prolyl-4-hydroxylase, prolyl-3-hydroxylase and lysyl hydroxylase. All three enzymes require Fe+2,O2, "-ketoglutarate, and ascorbate. - Two enzymes catalyze the glycosylation of the 5-OH of hyl: galactosyl- and glucosyl-- transferases (both require Mn+2 and utilizes the UDP derivatives of galactose and glucose). - Procollagen that is not properly hydroxylated is slowly secreted and rapidly degraded. Normal procollagen passes through the golgi and is secreted rapidly. |
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Term
Collagen Synthesis- Extracellular Processing |
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Definition
| - Procollagen have their carboxy (COOH) and amino (NH2) terminal ends removed by carboxypeptidase and aminopeptidase; both require divalent cations (e.g., Ca+2). - The collagen produced will spontaneously assembles into fibrils, followed by covalent crosslinking of the fibril strands. - Crosslinks are formed following oxidative deamination of lysine residues with subsequent adol condensation or Shiff base formation. - Lysyl oxidase catalyzes the only enzymatic step. |
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Term
| Adhesive Glycoproteins- General |
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Definition
- All of these proteins are linear and contain linear arrays of domains, each capable of binding certain molecules, e.g., collagen, protoglycans and fibrin. - These molecules will also bind different cells (through integrin- a membrane protein) - RGD (arg-gly-asp) sequences are found in fibronectin, laminin and other extracellular matrix proteins that bind to integrin receptors. - Synthetic RGD containing peptides will inhibft the binding of cells to fibroenectin or laminin. |
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Term
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Definition
-consist of two 250,000 dalton polypeptide chains - The most abundant adhesive glycoprotein - Fibronectin is necessary for cell migration during embryonic development. - Plays a crucial role in wound healing by attracting fibroblasts and other cells to the wound site. - May play a role in tissue metastasis by cancer cells |
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Definition
- contain 3 polypeptide chains of 1,000,000 daltons). - 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 through RGD sequences. - Laminin induces a number of physiological changes in cells, e.g., proliferation, migration, differentiation and cell spreading. |
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Term
| Proteoglycans (mucopolysaccharides) |
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Definition
- They are high molecule weight polyanionic complex consisting of glycosaminoglycans covalently attached to a core protein. - Proteoglycans play roles as lubricants, supportive elements in connective tissue, and in fluid balance. Because of their highiy charged nature, they produce a high viscosfty and elasticity by absorbing and associating with a large amount of water. |
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Definition
- There are six glycosaminoglvcans, each of which have long heterosaceharide chains made of repeating disaccharide units. - The disaccharide units are composed of hexosamines and uronic acids (which sometimes contain sulfate groups). |
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Term
The 6 GAG's and their functions - Heparan, Heparan Sulfate, Dermatan Sulfate, Chondroitin Sulfate, Keratan Sulfate, Hyaluronic Acid |
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Definition
- Dermatan sulfate and heparin are both antithrombic, i.e., they inhibit blood clotting. However, dermatan sulfate does not show whole body anticoagulation (minimally at best) and blood lipid clearing activity, where heparin has both activities. - Heparin increases the reactivity of antithrombin III, a protein that forms an inactive complex with thrombin, factor Xa or factor VIIa. One micromolar heparin is sufficient to prevent clotting. - Heparin sulfate is a component of connective tissue, particularly basement membrane (ft actually has fewer sulfates groups but more N-acetylation than heparin). Heparin is an intracellular component of mast cells that line arteries. |
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Term
| Disorders of Proteoglycan Degradation |
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Definition
- Like glycoproteins, the degradation of proteoglycans requires the action of proteases, glycosidases, deacetylases and sulfatases, which are primarily found in lysosomes. - If any of the hydrolases is/are deficient, the result is an accumulation of proteoglycans or their incomplete breakdown products in tissues (mucopolysaccharidosis). Where the enzyme deficiency is identified, the breakdown product that accumulates will begin with the nonreducing end of the sugar moiety that would have been its substrate |
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