Phospholipid Surfaces

Fibrinogen is an acute phase reactant and thus its concentration is substantially increased in several clinical situations. When the fibrinogen concentration is increased, the action of thrombin on fibrinogen is faster—the consequence of the greater extent of saturation of thrombin with fibrinogen. 

Red blood cells are responsible for the color of the blood clot in vitro and also the clot that forms from blood released onto the skin. A clot formed from fibrin in the absence of entrapped red blood cells is a white, translucent gel. In vitro, fibrin forms a stringy mass that is easily wrapped around a glass rod. 

Noncovalently associated fibrin is physiologically unsatisfactory because the dissociation of the fibrin results in recurrent bleeding. Fibrin monomer dissociation is prevented by formation of covalent cross-links between different Fnllm molecules. The result of this covalent cross-linking is an insoluble fibrin and a stable hemostatic plug. These cross-links are formed by the action of factor Xllla, plasma, and/or platelet transglutaminase (see below). Multiple cross-links are formed among a chains of several different fibrin monomers. This creates a molecular species designated a polymer (see Fibrinolysis below). Two 

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Fig. 2. Generation of tenase and prothrombin complexes. PPL represents the anionic phospholipid surface provided by the platelets (platelet phospholipid). Cleavage of prothrombin by the prothrombinase complex results in the formation of thrombin and the release of a small fragment called prothrombin fragment 1.2 (PFI.2).

Xiang, T.-X. Anderson, B. D., Phospholipid surface density determines the partitioning and permeability of acetic acid in DMPC cholesterol bilayers, J. Membrane Biol. 148, 157-167 (1995). 

Foss BJ, Nalum Naess S, Sliwka HR, and Partali V. 2003. Stable and highly water-dispersible, highly unsaturated carotenoid phospholipids—Surface properties and aggregate size. Angewandte Chemie-International Edition 42(42) 5237-5240. 

Isaacs, B.S., Husten, E.J., Esmon, C.T., and Johnson, A.E. (1986) A domain of membrane-bound blood coagulation factor Va is located far from the phospholipid surface. A fluorescence energy transfer measurement. Biochemistry 25, 4958-4969. 

That is, nonionic surfactants caused an increase in the Stokes radius (R) of the particles due to penetration of the phospholipid surface layer and unfolding of apoprotein B molecules leading to particle assymetry at molar ratios of surfactant LDL2 of ca. 1000/1. At higher molar ratios, corresponding to 1-2 moles surfactant per mole of phospholipid, ionic surfactants and nonionics with HLB values < 14.6 caused rapid decreases in the Stokes radius due to breakdown of LDL2 into the lipid surfactant and protein surfactant micelles. 

The clotting factors are protein molecules. Activation mostly means proteolysis (cleavage of protein fragments) and, with the exception of fibrin, conversion into protein-hydrolyzing enzymes (proteases). Some activated factors require the presence of phospholipids (PL) and Ca + for their proteolytic activity. Conceivably, Ca + ions cause the adhesion of factor to a phospholipid surface, as depicted in C. Phospholipids are contained in platelet factor 3 (PF3), which is released from ag-Lullmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

Vitamin K promotes the hepatic y-car-boxylation of glutamate residues on the precursors of factors II, VII, IX, and X, as well as that of other proteins, e.g., protein C, protein S, or osteocalcin. Carboxyl groups are required for Ca +-mediat-ed binding to phospholipid surfaces (p, 142). There are several vitamin K derivatives of different origins Ichlorophyllous plants I<2 from gut bacteria and I<3 (menadione) synthesized chemically. All are hydrophobic and require bile acids for absorption. 

I agree with Professor McConnell that phospholipid phase transitions may play a role in controlling the activity of a membrane-bound enzyme. However, the case cited is somewhat ambiguous, since porcine phospholipase A2 is a soluble enzyme acting on a phospholipid surface. The major effect of the phase transition in this case is to alter the nature of the substrate rather than the intrinsic catalytic activity of the enzyme. 

The major lipoproteins of insect hemolymph, the lipophorins, transport diacylglycerols. The apolipo-phorins have molecular masses of -250, 80, and sometimes 18 kDa.34-37a The three-dimensional structure of a small 166-residue lipophorin (apolipophorin-III) is that of a four-helix bundle. It has been suggested that it may partially unfold into an extended form, whose amphipathic helices may bind to a phospholipid surface of the lipid micelle of the lipophorin 35 A similar behavior may be involved in binding of mammalian apolipoproteins. Four-helix lipid-binding proteins have also been isolated from plants.38 See also Box 21-A. Specialized lipoproteins known as lipovitellins... 

The tenase complex is formed by the activated forms of the blood coagulation factors VIE and IX. It forms on a phospholipid surface in the presence of calcium and is responsible for the activation of factor X. Tenase is a contraction of ten and the suffix -ase , used for enzymes... 

Calcium and phospholipid. Required for the tenase and prothrombinase complexes to function. Calcium mediates the binding of the complexes via the terminal y-carboxy residues on factor Xa and factor IXa to the phospholipid surfaces expressed by platelets, as well as those procoagulant microparticles or microvesicles shed from them. 

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