Phospholipids common structural features

Cholesterol, which is largely insoluble in aqueous m a, travels through the blood circulation in the form of Upoprotein complexes. The plasma lipoproteins are a family of globular particles that share common structural features. A core of hydrophobic lipid, principally triacylglycerols (triglycerides) and cholesterol esters, is surrounded by a hydrophilic monolayer of phospholipid and protein (the apolipoproteins) [1-3]. Lipid-apolipoprotein interactions, facihtated byi amphi-pathic protein helices that segregate polar from nonpolar surfaces [2,3], provide the mechanism by which cholesterol can circulate in a soluble form. In addition, the apolipoproteins modulate the activities of certain enzymes involved in Upoprotein metabolism and interact with specific cell surface receptors which take up Upopro-teins by receptor-mediated endocytosis. Differences in the Upid and apoUpoprotein compositions of plasma Upoproteins determine their target sites and classification based on buoyant density. 

Phospholipase D (PLD, EC 3.1.4.4) hydrolyses phospholipids, liberating phosphatidic acid (PA) and the alcohol moiety which participates in the ester linkage (choline, ethanolamine,glycerol or inositol). The enzyme was found to be widespread in the plant kingdom (1). A number of recent studies which investigated the putative roles of these phospholipases suggest common structural features between PLDs of different plant origins. 

Problem 19.33. Ionic head portions are not present in all membrane lipids. The other phospholipids, the plasmalogens and sphingomyelins, are like the phosphoglycerides in having an ionic head and two nonpolar tails, but the glycolipids and cholesterol do not possess ionic heads. What is the structural feature common to all membrane lipids ... 

The most common structure observed is the so-called bimolecular leaflet or phospholipid bilayer. The structure is analogous to the neat phase of the lyotropic liquid crystals and is shown schematically in Fig. 5. The most prominent feature of this structure is the arrange-... 

The one and only distinctive feature of lipids is that they are all totally hydrophobic (water fearing), or nearly so. They generally will not chemically interact with water and therefore will not dissolve in water. Chemically, lipids fit into several categories, each of which is structurally unique. Common types of lipids include triacylglycerols, phospholipids, and steroids. 

Membranes are composed of lipids and proteins in varying combinations particular to each species, cell type, and organelle. The fluid mosaic model describes features common to all biological membranes. The lipid bilayer is the basic structural unit. Fatty acyl chains of phospholipids and the steroid nucleus of sterols are oriented toward the interior of the bilayer their hydrophobic interactions stabilize the bilayer but give it flexibility. 

It is clear that the particular approach to molecular similarity employed here can be used to rationalise HIVl virology data for the famiUes of phospholipids considered and even to make some successful predictions of active compounds. Preliminary results for various AZT derivatives (reverse transcriptase inhibitors) are also encouraging. The active compounds all feature an -N3 group. Nevertheless, comparisons of the HOMOs, which are localised in the thymine rings, can be used to distinguish easily between active and inactive compounds. Similarly, it has proved possible to identify features that are common to various, structurally-dissimilar, non-nucleoside reverse transcriptase inhibitors. 

Because altered sodium channels have been implicated in kdr and kdr-like resistance phenomena in insects, basic research on the biochemistry and molecular biology of this molecule, which plays a central role in normal processes of nervous excitation in animals, is of immediate relevance. The results of recent investigations of the voltage-sensitive sodium channels of vertebrate nerves and muscles have provided unprecedented insight into the structure of this large and complex membrane macromolecule. Sodium channel components from electric eel electroplax, mammalian brain, and mammalian skeletal muscle have been solubilized and purified (for a recent review, see Ref. 19). A large a subunit (ca. 2 60 kDa) is a common feature of all purified channels in addition, there is evidence for two smaller subunits ( Jl and J2 37-39 kDa) associated with the mammalian brain sodium channel and for one or two smaller subunits of similar size associated with muscle sodium channels. Reconstitution experiments with rat brain channel components show that incorporation of the a and pi subunits into phospholipid membranes in the presence of brain lipids or brain phosphatidylethanolamine is sufficient to produce all of the functional properties of sodium channels in native membranes (AA). Similar results have been obtained with purified rabbit muscle (45) and eel electroplax (AS.) sodium channels. 

The phospholipid bilayer, the basic structural unit of biomembranes, is essentially impermeable to most water-soluble molecules, ions, and water itself. After describing the factors that influence the permeability of lipid membranes, we briefly compare the three major classes of membrane proteins that Increase the permeability of biomembranes. We then examine operation of the simplest type of transport protein to Illustrate basic features of protein-mediated transport. Finally, two common experimental systems used in studying the functional properties of transport proteins are described. 

In this chapter, the authors describe the composition, structural organization, and general functions of biological membranes. After outlining the common features of membranes, a new class of biomolecules, the lipids, are introduced in the context of their role as membrane components. The authors focus on the three main kinds of membrane lipids—the phospholipids, glycolipids, and cholesterol. The amphi-pathic nature of membrane lipids and their ability to organize into bilayers in water are then described. An important functional feature of membranes is their selective permeability to molecules, in particular the inability of ions and most polar molecules to cross membrane bilayers. This aspect of membrane function is discussed next and will be revisited when the mechanisms for transport of ions and polar molecules across membranes is discussed in Chapter 13. 

Fig. 1. Insulin receptor. Structure of the precursor polypeptide of the insuiin receptor. A sequence of basic amino acids (in this case Argg, LySg42 Argg43) at the junction of the transmembrane sequence and the cytoplasmic domain is a common feature of transmembrane proteins. It is thought that they interact with polar groups of phospholipids on the membrane surface.

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