Zwaal et al on the clotting disorder, Scott Syndrome. 1. What is meant by lipid
ID: 93020 • Letter: Z
Question
Zwaal et al on the clotting disorder, Scott Syndrome. 1. What is meant by lipid bilayers having a “sidedness” to them, or another way of stating this? 2. If blood clotting factors are essentially just floating around in the blood, why are they not constantly causing blood clots? 3. Phosphatidylserine (PS) provides the most active catalytic surface for forming coagulation factor complexes. PS is generally located on the cytoplasimic surface of blood and endothelia cell membranes. What would happen if PS was always located on the outside of the cell membrane? 4. How do the three enzymes described in the paper determine sidedness of the various types of phospholipids? 5. How does the presence of Ca2+ affect phospholipid asymmetry? 6. What causes the Scott syndrome?
Explanation / Answer
Lipid Bilayers have a "sidedness" to them. It means the two membrane surfaces are asymmetric in nature.Two sides of the membrane have different characteristics.The proteins exposed at both sides of bilayer are different from each other with different structure and function. Blood clotting factors do not form clots normally in the blood because the platelet activation and coagulation cascade reactions occur only in response to an injury to the blood vessels that damages the endothelium. When endothelium gets damaged, the underlying collagen gets exposed to circulating platelets. Binding of collagen with glycoproteins of platelets triggers a series of signalling cascade which ultimately results into adherence of platelets to the site of injury forming a clot. In absence of injury, platelets remain floating in blood in an inactive state. And the enzymes involved in the process also remain inactive, normally. Presence of PS on the outer side of cell membrane, may increase Tissue factor (TF) coagulant activity at the cell surface. TF is an important part of the factor VIIa-TF enzyme complex that triggers the coagulation cascade reactions and transduces cell signalling by activating protease activated receptors. The names of three enzymes are not mentioned in question. Though Many enzymes are found at both sides of membrane but few are associated with inner surface only(like spectrin, ankyrin). Proteins are linked to plasma membrane by GPI anchor can be easily distinguished by use of Phosphatidylinositol specific phospholipase C enzyme. This enzymes cuts the GPI anchor releasing the proteins free. Many enzymes catalyze the transport of anions across the membrane. When there is Ca2+ concentrations > 10mM, fusion of lipid asymmetric RBCs is established. Fusion of lipid-symmetric RBC membranes was established at >1.5 mM concentration of Ca2+. Scott syndrome is caused by defects in platelet mechanism that supports blood coagulation.
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