Transporters cellular

Peptoid-Based Drug Delivery and Molecular Transporters Cellular Uptake... 

Endocytosis / Phagocytosis Active Transport Cellular Proliferation Intracellular Cytokine Production Intracellular Signal Transduction Intracellular Free Ions (e.g., Na, K, Ca)... 

Phosphorus is one of the inorganic macronutrients in all known forms of life. Inorganic phosphorus in the form of phosphate (PO/ ) plays a major role in vital biological molecules, such as DNA and RNA. Living cells also utilize phosphate to transport cellular energy via adenosine triphosphate (ATP). Phospholipids are the main structural components of all cellular membranes. Calcium phosphate salts are... 

Conjugation of lipophilic xenobiotics to polar cellular constituents renders the xenobiotic more water-soluble. While the lipophilic parent xenobiotics could readily diffuse into the cells, the increase in polarity associated with conjugation greatly reduces the ability of the compound to diffuse across the lipid bilayer of the cell membrane thus trapping the compound within the cell. The polar conjugates must therefore rely upon active transport processes to facilitate efflux from the cell. Hepatocytes, as well as other cells involved in chemical detoxification, are rich with members of the ATP-binding cassette superfamily of active transport proteins (ABC transporters). Cellular efflux of xenobiotics by these transporters is often referred to as Phase III elimination because Phase I or II detoxification processes often precede and are a requirement of Phase III elimination. A detailed description and discussion of elimination and transporters is presented in Chapter 15. 

Meredith, D. and Boyd, C.A. (2000) Structure and function of eukaryotic peptide transporters. Cellular and Molecular Life Sciences, 57 (5), 754—778. 

Apart from the a-TTP-mediated VLDF incorporation and export, secretion of a-tocopherol from cultured cells is also mediated by ABCAl and other not yet characterized processes. ABCAl is an ATP-binding cassette protein that transports cellular cholesterol and phospholipids to lipid-poor high-density lipoproteins (HDF) and apolipoproteins such as apoA-I."" In this study, cells lacking an active ABCAl pathway markedly increased secretion of a-tocopherol to apoA-I after overexpression of ABCAl. 

Figure 5 Schematic of presynaptic mechanisms involved with the uptake of dopamine (DA). MAO, monoamine oxidase (located on the surface of the mitoehondrion) VMAT, vesicular monoamine transporter DAT dopamine transporter. Cellular maehinery has been enlarged to show detail.

The ready reversibility of this reaction is essential to the role that qumones play in cellular respiration the process by which an organism uses molecular oxygen to convert Its food to carbon dioxide water and energy Electrons are not transferred directly from the substrate molecule to oxygen but instead are transferred by way of an electron trans port chain involving a succession of oxidation-reduction reactions A key component of this electron transport chain is the substance known as ubiquinone or coenzyme Q... 

In the chloride shift, Ck plays an important role in the transport of carbon dioxide (qv). In the plasma, CO2 is present as HCO, produced in the erythrocytes from CO2. The diffusion of HCO requires the counterdiffusion of another anion to maintain electrical neutraUty. This function is performed by Ck which readily diffuses into and out of the erythrocytes (see Fig. 5). The carbonic anhydrase-mediated Ck—HCO exchange is also important for cellular de novo fatty acid synthesis and myelination in the brain (62). 

In an oligonucleotide having n backbone linkages, this gives rise to 2 isomers that vary in their mechanism of action, cellular transport, as well as pharmacokinetics (53). Some of the most frequently encountered backbone modifications are Hsted in Table 1. 

The rate of side-chain cleavage of sterols is limited by the low solubiUty of substrates and products and thek low transport rates to and from cells. Cyclodextrins have been used to increase the solubiUties of these compounds and to assist in thek cellular transport. Cyclodextrins increase the rate and selectivity of side-chain cleavage of both cholesterol and P-sitosterol with no effect on cell growth. Optimal conditions have resulted in enhancement of molar yields of androsta-l,4-diene-3,17-dione (92) from 35—40% to >80% in the presence of cyclodextrins (120,145,146,155). 

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial dehvery of retinol by holo-B >V (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation of cells (56). 

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