Membrane of cell

The diversity in primary, secondary, tertiary, and quaternary stmctures of proteins means that few generalisations can be made concerning their chemical properties. Some fulfil stmctural roles, such as the collagens (found in bone) and keratin (found in claws and beaks), and are insoluble in all solvents. Others, such as albumins or globulins of plasma, are very soluble in water. Still others, which form part of membranes of cells, are partly hydrophilic ( water-loving , hence water-soluble) and partly lipophilic ( lipid-loving , hence fat-soluble). 

The glycosphingolipids (GSLs) are sugar-containing lipids built on a backbone of ceramide they include galactosyl- and glucosylceramide (cerebrosides) and the gangliosides. Their structures are described in Chapter 14. They are mainly located in the plasma membranes of cells. 

Certain proteoglycans (eg, heparan sulfate) are associated with the plasma membrane of cells, with their core proteins acmally spanning that membrane. In it they may act as receptors and may also participate in the mediation of cell growth and cell-cell communication. The attachment of cells to their substramm in cul-mre is mediated at least in part by heparan sulfate. This proteoglycan is also found in the basement membrane of the kidney along with type IV collagen and laminin... 

Many of the toxins obtained from coelenterates and echinoderms, because of their hemolytic or cytotoxic actions, are assumed to have a general disruptive action on cell membranes. However, since many of these toxins are capable of forming pores or channels in the plasma membrane of cells, their cytolytic actions may be a result of this highly selective action. On the other hand, the saponins from starfish and sea cucumbers have a direct lytic action as a result of their detergent action on the integrity of cells. 

It is well known that chemical compo.sition of rhizosphere solution can affect plant growth. Particularly, uptake of nutrients may be considerably influenced by the ionic concentration of the rhizosphere solution (40). Despite the difficulty of defining the exact concentration of ions in the rhizosphere surrounding each root (or even root portion), it has been unequivocally demonstrated that plants have evolved mechanisms to cope with the uneven distribution of ions in the root surrounding in order to provide adequate supply of each essential nutrient (41). These mechanisms include expression of transporter genes in specific root zones or cells and synthesis of enzymes involved in the uptake and assimilation of nutrients (40,43). Interestingly, it has been shown that specific isoforms of the H -ATPase are expressed in the plasma membrane of cell roots it has been proposed that the expression of specific isoforms in specific tissues is relevant to nutrient (nitrate) acquisition (44) and salt tolerance (45). 

A number of substances have been discovered in the last thirty years with a macrocyclic structure (i.e. with ten or more ring members), polar ring interior and non-polar exterior. These substances form complexes with univalent (sometimes divalent) cations, especially with alkali metal ions, with a stability that is very dependent on the individual ionic sort. They mediate transport of ions through the lipid membranes of cells and cell organelles, whence the origin of the term ion-carrier (ionophore). They ion-specifically uncouple oxidative phosphorylation in mitochondria, which led to their discovery in the 1950s. This property is also connected with their antibiotic action. Furthermore, they produce a membrane potential on both thin lipid and thick membranes. 

Abstract The interplay between three disciplines, organic synthesis, biophysics and cell biology in the study of protein lipidation and its relevance to targeting proteins towards the plasma membrane of cells in precise molecular detail is described in this concept. This interplay is highlighted using the Ras protein as a representative example. Included herein is the development of methods for the synthesis of Ras-derived peptides and fully functional Ras proteins, the determination of the biophysical properties, in... 

This chapter highlights the interplay between organic synthesis, biophysics and cell biology in the study of protein lipidation and its relevance to targeting proteins towards the plasma membrane of cells in precise molecular detail. 

The dielectric breakdown offers a third method for the build up of cell models. Zimmermann and coworkers could show that under appropriate conditions cells can be fused with other cells and liposomes ( 9). By means of this method lipids from artificial liposomes can be incorporated into the membrane of cells (80). 

Yeagle, P. L. The membranes of cells Academic Press San Diego, 1993. 

Substrate availability to the cell is affected by the supply of raw materials from the environment. The plasma membranes of cells incorporate special and often specific transport proteins (translocases) or pores that permit the entry of substrates into the cell interior. Furthermore pathways in eukaryotic cells are often compartmentalized within cytoplasmic organelles by intracellular membranes. Thus we find particular pathways associated with the mitochondria, the lysosomes, the peroxisomes, the endoplasmic reticulum for example. Substrate utilization is limited therefore by its localization at the site of need within the cell and a particular substrate will be effectively concentrated within a particular organelle. The existence of membrane transport mechanisms is crucial in substrate delivery to, and availability at, the site of use. 

The Meyer-Overton hypothesis proposed that once a sufficient number of anaesthetic molecules were dissolved in the lipid membranes of cells within the central nervous system, anaesthesia would result by a mechanism of membrane disruption. While an interesting observation, there are several exceptions to the rule that make it insufficient to account fully for the mechanism of anaesthesia. 

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

Antioxidants These are naturally occurring compounds that have the ability to lower the levels of free radicals they include vitamins C and E, the carotenoids and the flavonoids. Vitamin E and the carotenoids are particularly important in preventing oxidation of the unsaturated fatty acids within the LDL particle and within membranes of cells. 

Figure 6.13 shows the concentrations of organic compounds in water that are sufficient to immobilize tadpoles, and their values of log P or the partition coefficient between octanol and water. Thymol, with a log P of 1000, is 10,000 times more toxic than ethanol, which has a log P of around 0.3. A plausible explanation of this phenomenon lies in the structure of the membranes of cells, which are made of two layers of lipid, or fat, so that a more fat-soluble substance would find it easier to penetrate the cell and to cause damage. 

Figure 5.1 Growth factor receptors are illustrated here. Docking proteins—receptors for protein growth factors—are embedded in the outer membranes of cells. Binding of the specific growth factor triggers a cascade of biochemical signals that cause the cell to divide and express the proteins that give the cell specialized properties.

Propidium iodide can be used to assess plasma membrane integrity in annexin V apoptosis assays. It does not cross the plasma membrane of cells that are viable or in the early stages of apoptosis because of their plasma membrane integrity. In contrast, cells in the late stages of apoptosis or already dead have lost plasma membrane integrity and are permeable to PI for DNA staining (Fig. 5). In flow cytometric assays, another nucleic acid dye that can be used in place of PI for the exclusion of nonviable cells is 7-AAD. The advantage of 7-AAD over PI is its ability to be used in conjunction with phycoerythrin (PE)- and FITC-labeled monoclonal antibodies with minimal spectral overlap between the 7-AAD, PE, and FTTC fluorescence emissions. 

Inappropriate expression of class II MHC molecules on the membranes of cells that normally do not express class II MHC (eg, islet beta cells). Increased expression of MHC II may increase presentation of self peptides to T helper cells, which in turn induce CTL, TDTH, and B-lymphocyte cells that react against self antigens. 

Introducing hydrophilic groups (e.g., sulfonyl, carboxyl) or other bulky groups to increase the molecular size to >1000 Da, modify the planarity and shape, and/or render the molecule so polar that it cannot easily penetrate the lipid membrane of cells, should significantly reduce a chemical s absorption and bioactivation. 

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