Mammalian Membranes

The Major Lipids in Mammalian Membranes Are Phospholipids, Glycosphingolipids, Cholesterol... 

Cholesterol is an essential component of mammalian membranes. It is obtained from the diet or can be synthesized from acetyl-CoA. 

Kuhn, M. Structure, regulation and function of mammalian membrane guanylyl cyclase receptors, with a focus on guanylyl cyclase-A. Circ. Res. 93 700-709, 2003. 

Tab. 1.3 Application of expression systems for mammalian membrane proteins...

C. D. Stubbs and A. D. Smith, The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function, Biochim. Biophys. Acta 779, 89-137 (1984). 

Taussig, R. and Gilman, A,G. Mammalian membrane-boand adenylyl cyclases (1995) J. Biol. Chem. 270, 1-4... 

Cholesterol is the most common steroid of mammalian membranes. It is formed biologically from lanosterol, as shown. Ergosterol is the most common steroid of fungal membranes. It differs from cholesterol by the presence of two additional double bonds that affect its three dimensional structure. Also shown are three so-called steroid hormones, andros-terone, estradiol, and testosterone. Note the presence of an aromatic A-ring in estradiol. 

Skou had established previously that such anesthetics inhibited certain membrane-bound enzymes found in the membrane fraction isolated from nerve homogenates. He decided to study the endogenous ATPase activity as a possible target for future work, initially thinking that it might be the sodium channel. Luckily, since he lacked access to squid giant axons, he used the easily-obtained mixed nerve from the claw of the crab for this purpose. This proved to be a fortuitous choice since, in contrast to mammalian membrane fragments, these did not spontaneously reseal to form closed vesicles. This allowed substrates added to the... 

Bacterial membranes have a much more complex construction than mammalian membranes. This enables bacteria to survive in the various environments of host organisms. Knowledge of the composition and functioning of bacterial membranes is therefore essential to the development of anti-infective drugs. In order to be effective, antibacterial agents not only have to have optimal pharmacokinetic properties such as uptake and distribution in the patient, but they must also be able to cross an additional barrier, the cell wall of the bacteria, so that they can reach the target site. This additional barrier is remarkable on account of its rigidity and permeability. The construction and structural uniqueness of this barrier is briefly described below. 

Artificial membranes are used to study the influence of drug structure and of membrane composition on drug-membrane interactions. Artificial membranes that simulate mammalian membranes can easily be prepared because of the readiness of phospholipids to form lipid bilayers spontaneously. They have a strong tendency to self-associate in water. The macroscopic structure of dispersions of phospholipids depends on the type of lipids and on the water content. The structure and properties of self-assembled phospholipids in excess water have been described [74], and the mechanism of vesicle (synonym for liposome) formation has been reviewed [75]. While the individual components of membranes, proteins and lipids, are made up of atoms and covalent bonds, their association with each other to produce membrane structures is governed largely by hydrophobic effects. The hydrophobic effect is derived from the structure of water and the interaction of other components with the water structure. Because of their enormous hydrogen-bonding capacity, water molecules adopt a structure in both the liquid and solid state. 

Cholesterol is an essential constituent of mammalian membranes and is required for their normal functioning. While a large number of experimental studies have been undertaken to investigate the effect of cholesterol on the physical properties of phospholipid membranes, our understanding of changes in these properties at a molecular level is still incomplete. Computer simulations can help in this respect, but in relation to the importance of cholesterol relatively few have been undertaken. This can be explained by the fact that the influence of cholesterol is highly dependent on its molar ratio compared with the phospholipids, also on the type of phospholipid used, and new phases appear in presence of cholesterol, thus making the simulation of such process rather difficult. 

DeLuca H (1977) The direct involvement of vitamin A in glycosyl transfer reactions of mammalian membranes. Vitamins and Hormones 35,1-57. 

Blazyk JF, Steim JM. Phase transitions in mammalian membranes. Biochim. Biophys. Acta 1972 266 737-741. 

Jidenko M, Nielsen RC, Sorensen TL, Moller TV, le Maire M, 67. Nissen P, Jaxel C. Crystallization of a mammalian membrane protein overexpressed in Saccharomyces cerevisiae. Proc. Natl. 

This 3.6-A stmcture of Aquaporin-4 (Fig. 3c) was determined by electron crystallography of double-layered 2-D crystals (56). Features in the stmcture show that Aquaporin-4 can form membrane junctions, and they suggest for the first time its role in cell adhesion. This stmcture is of additional interest in that it is the first stmcture of a multispanning mammalian membrane protein obtained by purely recombinant methods. 

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