Phospholipids in biological membranes

Phosphatidylinositol 4-phosphate (PI-4-P, 3) is the second most abundant inositol phospholipid in biological membranes. It is a product of phosphorylation by four different species of PI 4-kinases (21), and it is a precursor to PI-4,5-P2 and PI-3,4,5-P3. These kinases are the two inositol lipids whose biological roles are understood best. The biological function of PI-4-P is not well known however, the studies in yeast indicate its role extends beyond the substrate for PI 5-kinase (21), such as regulation of vesicular trafficking and protein secretion from Golgi. PI-4-P is removed by the subsequent phosphorylation to PI-4,5-P2 or dephosphorylation to PI by ER-localized phosphatase (21). 

Figure 1. Molecular structure of types of phospholipid in biological membranes...

A new class of phosphatidylcholine analogues (6) and (7) derived from glyceric acid has been prepared for studies of conformation and interaction of phospholipids in biological membranes, using fluorescence energy transfer (FRET) techniques (Scheme 1)." ... 

There are other ways in which the lateral organization (and asymmetry) of lipids in biological membranes can be altered. Eor example, cholesterol can intercalate between the phospholipid fatty acid chains, its polar hydroxyl group associated with the polar head groups. In this manner, patches of cholesterol and phospholipids can form in an otherwise homogeneous sea of pure phospholipid. This lateral asymmetry can in turn affect the function of membrane proteins and enzymes. The lateral distribution of lipids in a membrane can also be affected by proteins in the membrane. Certain integral membrane proteins prefer associations with specific lipids. Proteins may select unsaturated lipid chains over saturated chains or may prefer a specific head group over others. 

Myo-inositol is one of the most biologically active forms of inositol. It exists in several isomeric forms, the most common being the constituent of phospholipids in biological cell membranes. It also occurs as free inositol and as inositol hexaphosphate (IP6) also known as phytate which is a major source from food. Rice bran is one of the richest sources of IP6 as well as free inositol. Inositol is considered to belong to the B-complex vitamins. It is released in the gastrointestinal tract of humans and animals by the dephosphorylation of IP6 (phytate) by the intestinal enzyme phytase. Phytase also releases intermediate products as inositol triphosphate and inositol pentaphosphate. Inositol triphosphate in cellular membrane functions as an important intra- and intercellular messenger, that merits its value as a nutritional therapy for cancer. 

An important characteristic of mammalian 15-LOX is its capacity to oxidize the esters of unsaturated acid in biological membranes and plasma lipoproteins without their hydrolysis to free acids. Jung et al. [19] found that human leukocyte 15-LOX oxidized phosphatidylcholine at carbon-15 of the AA moiety. Soybean and rabbit reticulocyte 15-LOXs were also active while human leukocyte 5-LOX, rat basophilic leukemia cell 5-LOX, and rabbit platelet 12-LOX were inactive. It was suggested that the oxygenation of phospholipid is a unique property of 15-LOX. However, Murray and Brash [20] showed that rabbit reticulocyte... 

The studies on phospholipid bilayers with defined amounts of charged component are helpful to explain the partition characteristics in biological membranes. Liposome water partition data of propranolol in lipids from kidney epithelial cells (a common model system in pharmaceutical sciences for the uptake into the gastrointestinal tract) have been successfully described with partition models developed for pure bilayers or defined mixtures [159]. Since lipophilic cations and anions can be used as probes for the membrane potential, their interaction with microbial and mitochondrial membranes has been studied... 

Casadio, R., Venturoli, G. and Melandri, B. A. (1988). Evaluation of the electrical capacitance in biological membranes at different phospholipid to protein ratios -a study in photosynthetic bacterial chromatophores based on electrochromic effects, Eur. Biophys. J., 16, 243-253. 

Biological membranes consist of a bilayer of phospholipids in which membrane proteins are either embedded (integral proteins) or simply adsorbed (boundary proteins) (1) (Figure 1.). These systems fulfill a variety of functions oT basic importance. One of the most significant is the compartimentation via the formation of cells and cell subunits based on the self organization of membranes (hydrophobic effect (2j). 

Figure19.1 A schematic diagram of a plasma membrane. Integral proteins are embedded in a bilayer composed of phospholipids (shown, for clarity, in much greater proportion than they have in biological membranes) and cholesterol. The carbohydrate components of glycoproteins and glycolipids occur only on the external face of the membrane. (Reproduced from D. Voet and J. G. Voet, Biochemistry, 3rd edn, 2004. 2004, Donald and Judith G Voet. Reprinted with permission of John Wiley and Sons, Inc.)...

Schlenkrich, M., Brickmann, J., MacKerell Jr., A. D., and Karplus, M. (1996) An empirical potential energy function for phospholipids criteria for parameter optimization and application. In Biological membranes a molecular perspective from computational and experiment, Merz Jr., K. M. and Roux, B. (eds.), Birkhauser, Boston, 31-81. 

The rates of lateral diffusion of phospholipids in lipid bilayer membranes, and in biological membranes, were first measured using spin-labeled lipids.26 50 10 11 9 In general, these rates have been determined by incorporating spin-labeled lipids such as (V) and (VI) in phospholipid bilayers, or multilayers. The paramagnetic resonance spectra of labels such as (V), as well as the nuclear resonance spectra of other lipids in membranes containing (V), depend on the concentration c of the label in the membrane and the rate of lateral motion of the lipids. Two methods... 

The present studies lend further credence to the concept that Ca-+— ATP-phospholipid complexes can occur in biological membranes. It would also appear that the presence of a nucleotide such as ATP may be... 

Two main types of lipids occur in biological membranes phospholipids and sterols. The predominant phospholipids in most membranes are phosphoglycerides, which are phosphate esters of the three-carbon alcohol, glycerol. A typical structure is that of phosphatidylcholine (lecithin) ... 

Due to their amphipathic nature, phospholipids spontaneously form ordered structures in water. When phospholipids are agitated in the presence of excess water, they tend to aggregate spontaneously to form bilayers, which strongly resemble the types of structures they form in biological membranes. 

Be familiar with the composition and structure of biologic membranes. Be able to place the various phospholipids in the membrane bilayer. Know the function and position of membrane proteins and their possible movements. Know how membrane fluidity is controlled. Know the nature of various mechanisms to transport substances across membranes, receptor-mediated endocytosis, active and facilitated transport, ionophores, and the various types of channels. Be able to solve simple mathematical problems by creating solute gradients across membranes. Know the names of substances that inhibit the various modes of transport across membranes. 

The corresponding dimeric analogues of lipids are also important, owing to their occurrence in biological membranes. For example cardiolipins, which constitute a class of complex dimeric phospholipids that occur mainly in the... 

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