Cell membranes through

Ca2+ influx initiates protein and membrane associations by several different mechanisms. Allosteric regulation of the hydrophobicity of protein-binding surfaces frequently occurs. One of the best studied examples is the Ca2+-dependent binding of calmodulin to other proteins (Ch. 22). Annexins are a family of proteins that exhibit Ca2+-dependent associations with cell membranes through direct interaction with phospholipids, and conversely, interactions with phospholipids increase their affinities for Ca2+ [7]. 

For a complex multicellular organism to function, cells must rapidly respond to messages from other regions of the organism. These messages, often in the form of hormones, arrive at the cell membrane through the aqueous environ-... 

HIV-1 binds to the cell membrane through interaction of the viral envelope glycoprotein (gp) 120 with CD4 molecules on the cell smface. HIV-1 then fuses wifh fhe cell membrane as a result of interaction of gp 120 with chemokine receptors (CCR5 or CXCR4) on the cell. CCR5... 

Figure 21.9 The mitogen-activated protein kinase cascade (MAP kinase cascade). The active protein Ras activates Raf by promoting its recruitment to a cell membrane. Through a series of phosphorylations MAP kinase is activated as follows MAP kinase kinase kinase (Raf) phosphorylates MAP kinase kinase which, in turn, phosphorylates MAP kinase, the final target enzyme. MAP kinase phosphorylates transcription factors for genes that express proteins involved in proliferation. Another nomenclature for the enzymes is also used raf is MEKK MAPKK is MEK and finally ERK is MAP kinase (ERK is the abbreviation for extracellular-signal-related kinase) For comparison, the reader is referred to the metabolic phosphorylase cascade, which is discussed in Chapter 12 (Figure 12.12).

As chemicals pass into and out of cells, they must cross the cell membrane that keeps all of the cell contents securely inside, but which allows some materials to pass (Figure 2.1). Chemicals can move through the cell membrane through one of several mechanisms. 

The main obstacle to percntaneous penetration of water and xenobiotics is the onter-most membrane of the epidermis. This is called the stratum comeum. All entry of substances through the stratum comeum occurs by passive diffusion across several cell layers. The locus of entry varies, depending on the chemical properties of xenobiotics. Polar substances are believed to penetrate cell membranes through the protein filaments nonpolar ones enter through the hpid matrix. Hydration of the stratnm comenm increases its permeability for polar substances. Electrolytes enter mainly in a nonionized form, and thus the pH of the solution applied to the skin affects permeabUity. Many hpophdic substances, such as carbon tetrachloride and organophosphate insecticides, readily penetrate the stratum comeum. Pretreatment of the skin with solvents, snch as dimethyl sulfoxide, methanol, ethanol, hexane, acetone, and, in particular, a mixture of chloroform and methanol, increases permeability of the skin (Loomis, 1978). 

Many bixxer compounds contain both hydrophobic and hydrophilic sites which can alter cell membranes through penetration. There is a correlation between bitter intensity and hydrophobicity-solubility indexes such as fee octanol/water partition coefficient, lo (7). Penetration may directly affect cAMP phosphodiesterase as part of fee transduction process (see below). A bitter receptor protein may be involved wife certain bitters, such as specific structural requirements wife fee bitter tasting dipeptides and denatonium salts (27). The latter is used in some consumer products to avoid accidental ingestion. A receptor mechanism is also supported by fee existence of a genetic "taste blindness" for some bitter materials (see below). 

ROS can cause profound damage to lipids within cell membranes through lipid peroxidation. The mechanism involves free radical-mediated abstraction of a hydrogen atom from polyunsaturated fatty adds, such as linoleic acid (Scheme 3.11). A methylene group located between two double bonds in such a... 

The sample is disrupted completely and distributed over the surface as a function of interactions with the support, the bonded phase, and the tissue matrix components themselves. The solid support acts as an abrasive that promotes sample disruption, whereas the bonded phase acts as a lipophilic, bound solvent that assists in sample disruption and lysis of cell membranes. The MSPD process disrupts cell membranes through solubilization of the component phospholipids and cholesterol into the Cis polymer matrix, with more polar substituents directed outward, perhaps forming a hydrophilic outer surface on the bead. Thus, the process could be viewed as essentially turning the cells inside out and forming an inverted membrane with the polymer bound to the solid support. This process would create a pseudo-ion exchange-reversed-phase for the separation of added components. Therefore, the Cis polymer would be modified by cell membrane phospholipids, interstitial fluid components, intracellular components and cholesterol, and would possess elution properties that would be dependent on the tissue used, the ratio of Cis to tissue employed and the elution profile performed (99-104). 

The centrioles migrate to opposite poles of the cell and the mitotic spindle is formed, apparently joining the cell membrane through the centrioles to the centromere of each chromosome. Spindle fibres consist of one type of protein, tubulin, of molecular weight 60,000. It is the organisation of these molecules to form the mitotic spindle which is blocked by the drugs colchicine, colcemide, nocodazole, vincristine and vinblastine (Fig. 10.3) with the consequence that mitosis is arrested in metaphase. 

Figure 31-3. Free radicals resulting from the reaction of ferric iron with hydrogen peroxide can progress to damage cell membranes through lipid peroxidation (Britton, 1996). LH = polyunsaturated fatty acid R = free radical LOO = lipid per-oxyl radical LOOH = lipid peroxide.

The tethered bilayer offer improvements in both stability and in terms of its approximation of the true cell membrane through incorporation of tethering links... 

Human TNFa is a protein that exists in both soluble (157amino acids) and transmem-brane form (233 amino acids). Soluble TNFa is released from the cell membrane through a TNF-converting enzyme and exists as a ho-motrimer in aqueous solution (556,557). It is produced primarily by monocytes/macro-phages in response to various inflammatory stimuli, but can also be produced by other cell types, including T-cells, NK cells, dendritic cells, and endothelial cells. 

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