Plasma membrane with asymmetric

The maintenance of an asymmetric distribution of phospholipids across the plasma membrane with choline phospholipids predominating on the external surface and amino phospholipids confined to the cytoplasmic leaflet of the membrane has now been well estabhshed. The participation of... 

Figure 13. Schematic of the plasma membrane with a structural and functional asymmetric orientation of the molecular constituents (adapted from Refs. 89, 91, and 98). Aqueous medium = exterior.

The average human red cell plasma membrane is lipid-rich with 240 million PL molecules, 190 million cholesterol molecules, 12 million glyco-lipid molecules and only 4 million protein molecules (Lux and Glader, 1981). The PLs of the red cell plasma membrane are asymmetrically distributed in the bilayer. The choline-containing PLs, PC and sphingomyelin represent 40% and 15%, respectively, of the total PL, and are enriched in the outer leaflet. In contrast, the amino PLs, PE and phospha-tidylserine (PS) are exclusively confined to the inner leaflet and constitute 35% and 15%, respectively, of total PLs. 

The equivalent of the tryptic fragment of human transferrin receptor has been expressed in Chinese hamster ovary cells and its structure determined at a resolution of 0.32 nm (Lawrence et ah, 1999). The asymmetric unit of the crystals contains four transferrin receptor dimers. Interpretable electron density is found for the entire tryptic fragment except for Arg-121 at the amino terminus, and density is also seen for the first N-acetylglucosamine residue at each of the N-glycosylation sites. The transferrin receptor monomer is made up of three distinct domains, organized such that the dimer is butterfly shaped (Figure 5.10, Plate 7). The likely orientation of the dimer with respect to the plasma membrane has been assigned on the basis of the... 

The second class of AChEs exists as heteromeric assemblies of catalytic and structural subunits. One form consists of up to 12 catalytic subunits linked by disulfide bonds to filamentous, collagen-containing structural subunits. These forms are often termed asymmetric, since the tail unit imparts substantial dimensional asymmetry to the molecule. The collagenous tail unit links by disulfide bonding at its proline rich N-terminus through a coiled coil arrangement to the C-terminus of two of the catalytic subunits [30]. The tail unit associates with the basal lamina of the synapse rather than the plasma membrane. 

The lipids and proteins of membranes are inserted into the bilayer with specific sidedness thus membranes are structurally and functionally asymmetric. Many membrane proteins contain covalently attached oligosaccharides. Plasma membrane glycoproteins are always oriented with the carbohydrate-bearing domain on the extracellular surface. 

The modulation of synaptosomal plasma membranes (SPMs) by adriamycin and the resultant effects on the activity of membrane-bound enzymes have been reported [58]. Again DPH was used as fluorescence probe. Adriamycin increased the lipid fluidity of the membrane labeled with DPH, as indicated by the steady-state fluorescence anisotropy. The lipid-phase separation of the membrane at 23.3 °C was perturbed by adriamycin so that the transition temperature was reduced to 16.2 °C. At the same time it was found that the Na+,K+-stimulated ATPase activity exhibits a break point at 22.8 °C in control SPMs. This was reduced to 15.8 °C in adriamydn-treated SPMs. It was proposed that adriamycin achieves this effect through asymmetric perturbation of the lipid membrane structure and that this change in the membrane fluidity may be an early key event in adriamycin-induced neurotoxicity. 

In neurons, the SNARE complex consists of three main proteins the v-SNARE synaptobrevin or VAMP (vesicle-associated membrane protein), and two t-SNAREs, syntaxin and SNAP-25 (synaptosomal associated protein of 25 kD). Synaptobrevins traverse the synaptic vesicle membrane in an asymmetric manner a few amino acids are found inside the vesicle, but most of the molecule lies outside the vesicle, within the cytoplasm. Synaptobrevin makes contact with another protein anchored to the plasma membrane of the presynaptic neuron, syntaxin, which is associated with SNAP-25. Via these interactions, the SNARE proteins play a role in the docking and fusion of synaptic vesicles to the active zone. 

In the plasma membrane of animals (1), the amount of cholesterol is usually around 20-30 mol%. The rest of the lipids are mainly PC, PE, and sphingomyelin (SM) lipids, with smaller amounts of PS, PI, and glycolipids. These lipids are distributed asymmetrically across the membrane, because most cholesterol, PC, and glycolipids are located in the extracellular (outer) leaflet, whereas PS and PE lipids are located mainly in the intracellular (inner) monolayer. The lipid composition can be highly different in other organelles, however, as is the case in mitochondria (1), in which the mitochondrial membrane is composed of two (inner and outer) membranes. There, the amounts of cholesterol, SM, and PS are negligible most lipids are PC and PE. The major difference compared with plasma membrane is the concentration of cardiolipins. They are actually found only in bacterial and in mitochondrial membranes, where their numbers are significant even in mitochondria they are located mainly on the iimer membrane. 

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