Lecture #2 (11-12-06)
The original powerpoint presentation can be downloaded from the school server or from here (3.06 mb).
Introduction to Glycobiology
By Dr. Panin
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Glycobiology is associated with sugar, life, glycolysis, glucose, diabetes, and glycans, but it actually studies sugars that are attached to different molecules. These sugars are not free floating but can instead be attached to proteins either inside or outside of the cell or attached to the cell membrane’s lipids or proteins.
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Carbohydrates are ubiquitous, or omnipresent, modifications of eukaryotic cell surface proteins and lipids. This means that when a person looks at a cell membrane he will see the sugars coating the membrane, not the membrane itself (as in the lipid bilayer). |
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These are the different locations of glycans in the body. |
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Dr. Panin’s lab focuses on the extrinsic functions, or interactions between cells, resulting from glycan-lectin interactions. In this slide stability and solubility refers to the proteins that glycans attach to. Intracellular means within a cell; extracellular means between cells. |
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Epimerization is the change in orientation of bonded molecules around chiral carbons to get different hexoses. The resulting change is called an epimere. |
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The interaction between C1 and C5-OH in glucose forms a pyranose, or a six member carbon ring. |
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7
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Slides 7, 8 and 9 show examples of variations in the structure of sugars. |
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Slides 7, 8 and 9 show examples of variations in the structure of sugars. |
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Slides 7, 8 and 9 show examples of variations in the structure of sugars. |
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This slide shows some of the different configurations that exist in the glycosidic linkages between monosaccharides. |
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Chemical structures are very complex. Because of this, most people use the word structure when they talk about glycans since it relays the same information as the chemical structure. The bottom model shows all of the information as the top two except that it does not specify where the bonds occur between the molecules exactly. |
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This reaction involving glycosyltransferase in which sugar is attached to an acceptor is energetically unfavorable. Therefore it is coupled with the breaking of a terminal phosphate bond on an ATP molecule. This makes the entire reaction exergonic. Although the acceptor has a high energy bond between its two phosphate groups, ATP must be put in first to get the reaction started. |
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This slide shows that the same protein can bond to different sugars, which will affect the conformation and function of the enzyme and target different tissues. Also the same sugar can bond to different proteins, which will also alter the enzyme’s activity. |
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Three nucleotide bases and three amino acids can form six variations, but three hexoses can form 1,056 to 29,648 variations. This makes it difficult for researchers to develop a specific rule for decoding glycans. |
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The usual flow of information is from DNA to RNA to proteins that perform biological functions. However, this genetic information is indirectly expressed by formation of glycans, or polysaccharides, and their attachment to proteins by the means of glycosyltransferase. Lectins are specific proteins. |
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This shows that we are now moving on to the third point under extrinsic functions. |
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This slide shows and example of a proteoglycan. Proteoglycans are similar to DNA in that their code can be read by other cells. These proteoglycans work as a tag on the cell, for example in blood type, to allow for cell-to-cell recognition. All proteoglycans are long chains of disaccharides attached to a protein. Each always starts with attachment of xylose to the protein followed by the next three molecules. After this starts a long chain of disaccharide units that are varied by addition of sulfate, epimerization to IdoA, and other means. This allows for other cells to decode specifically what this tag means. Mutation in these tags can lead to abnormalities such as human multiple exostoses syndrome, characterized by tumors on the bones, as seen on the next slide. |
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19
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This slide compares the genes in flies to similar genes in mammals.
Higher quiality version of this slide can be found here. |
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This is a growing list of some of the problems caused by difficulties in cell-to-cell communication. |
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This slide concerns extracellular communication. Originally both serrate and delca could communicate with the notch before the fringe was added. After addition of the fringe, serrate can no longer communicate with the notch, altering the notch’s signaling. This can lead to some of the problems listed in the previous slide. |
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Moving on to some specific examples of how glycans mediate and modulate cell adhesion. |
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Normally, muscle cells attach to the extracellular matrix by the means of glycans. This allows the muscles to get the friction needed to produce movement. In muscular dystrophy, a disease affecting glycans, the glycans (in particulat the o-mannosyl glycans) do not form so the muscles have no way to produce to friction needed to move the body. |
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25
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Slides 25 and 26 examine more glycan-related mutation disorders. The number of these diseases reemphasizes the importance of the role of glycans in cell-to-cell communication and adhesion. |
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Slides 25 and 26 examine more glycan-related mutation disorders. The number of these diseases reemphasizes the importance of the role of glycans in cell-to-cell communication and adhesion.
Higher quality version of this slide can be found here. |
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This slide examines the role of glycans in blood type. O type blood has no glycan tag and is thus a universal donor. People with other types of blood, however, develop antigen tags specific to their blood type. If they were to undergo a blood transfusion in which the blood was not compatible to their type, the body would attack the "invading cells." |
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This slide just reemphasizes the relationship between structure and function in glycans. |