Diffusion into cells

Flavonoids can bind to plasma albumin,41 possibly decreasing their diffusion into cells.42 A 10% reduction of plasma albumin in older individuals43 44 could impact flavonoid distribution to tissues however, in fact, age-related decreases of albumin binding appear to have a minimal impact on the Vd of drugs 45... 

Recent observations have shown a direct relation between the pH of the blood and the depth of hepatic coma (VI). They are interpreted as evidence that the intracellular ammonia is increased in alkalosis because it is un-ionized ammonia and not ammonium ion which readily diffuses into cells. This finding may be a result of the central action of ammonium on the respiratory mechanism (F7), rather than the primary cause of the coma. In this sense it would seriously enhance the coma and set up a cycle which would be lethal. However this may be, there is no mechanism presented for the actual toxic effect of ammonia per se, and the data, except for the internal inconsistencies noted in a previous part of this discussion, would be compatible with the ketoglutarate depletion hypothesis. 

Some ligands do not interact principally with cell surface receptors, but diffuse into cells and bind to intracellular receptors in the cytoplasm. For example, ligand binding to cytoplasmic steroid receptors initiates a process that is not well understood but that involves the movement of steroid-bound receptor into the cell nucleus, where the receptor molecule interacts with genomic material, resulting in alterations in gene expression and protein synthesis. 

The area of the mesophyll cell walls across which CO2 can diffuse is considerably larger than the surface area of the leaf (Figs. 1-2 and 8-4). For the constricting effect caused by the stomata, we used Ast/A, the fraction of the leaf surface area that is occupied by stomatal pores. Here we will use the ratio Am s/A to indicate the increase in area available for CO2 diffusion into cells within a leaf compared to the leaf surface area, where Ames is the total area of the cell walls of mesophyll cells that is exposed to the intercellular air spaces, and A is the area of one side of the same leaf. More conveniently, A mesM can refer to the internal and the external areas of a part of the leaf that is examined microscopically. 

The thiosemicarbazone complexes CuPTSM and CuA-TSM, Fig. , have been used to image perfusion and hypoxia, respectively (36). It is believed that these compounds freely diffuse into cells. Reduction from Cu(II) to Cu(I) inside the cell causes the complex to faU apart, and the copper is trapped inside the ceU. The redox potential of CuATSM is lower than that of CuPTSM, and this redox potential is believed to be the root of the selectivity of CuATSM for hypoxic tissue. 

Although the cytotoxicity of cisplatin (and its derivatives) is accepted widely to be a result of its interactions with DNA, much is stiU unknown about the interactions of cisplatin on a cellular level. To begin with, the intracellular uptake of cisplatin is still the subject of much debate. Some smdies have suggested that cisplatin diffuses into cells passively, as uptake has been observed to be not saturable, not dependent on pH, and not inhibited by coadministration of structural analogs (6, 7). Other... 

What are the biochemical effects of the second messenger inositol 1,4,5-trisphosphate These effects were delineated by microinjecting IP3 molecules into cells or by allowing IP3 molecules to diffuse into cells whose plasma membranes had... 

Potassium ions diffuse into cells EjATP... 

After passive diffusion into cells, hydroxyurea inhibits nhonucleolide reductase, which results in deciea.sed levels ofdeoxyribonucleoiides.- Hydroxyurea may interfere with itic function of the cn-/yme by chelating with its ferrous iron (ofaclor. 

Esterase substrates have long been used as a measure of cell membrane integrity, with the fluorescent product being the marker retained. The one that has been used most often with fish cell lines is 5-carboxyfluorescein diacetate acetoxymethyl ester (CFDA-AM)174 CFDA-AM diffuses into cells rapidly and is converted by... 

According to Cavalier-Smith [57], secondary metabolites are most useful to the organisms producing them as competitive weapons and the selective forces for their production have existed even before the first cell. The antibiotics are more important than macromolecular toxins such as colicins and animal venoms because of their diffusibility into cells and broader modes of action. 

Oxygen diffuses into cells through the plasma membrane and, in muscle cells, binds to myoglobin. The oxy-... 

In addition to receptor-mediated metabolism of lipoproteins, which is the predominant mechanism for removal of intact lipoproteins, individual components of lipoproteins, particularly unesterified cholesterol, can diffuse into cells across the plasma membrane. Other minor uptake processes include so-called fluid-phase endocytosis, which does not involve binding of lipoproteins to specific cell surface proteins, and phagocytosis, in which lipoproteins attach to the cell surface via more or less specific forces, and are subsequently engulfed by the plasma membrane. 

Transport to tissues Cortisol is secreted into the blood stream where it is 90% bound to cortisol-binding globulin (CBG) and albumin. Active cortisol (remaining 10%) freely diffuses into cells where it exerts its actions via intracellular receptors. CBG plays an important role in regulating cortisol delivery and clearance. Dexamethasone has low affinity for CBG. It... 

Fatty acid diffusion into cells is also facilitated by a mass-action effect whereby their binding to a cytosolic/afiy acid binding protein reduces the free cytosolic concentration, thus promoting movement of fatty acids into the cell. This binding step needs to take place prior to activation of fatty acids to fatty-acyl CoA. 

Figure 6.4 Fluor-3 penla-acyloxymethyl ester passively diffuses into cells where it is cleaved by esterases and trapped as the parent compound, a calcium-sensitive fluorophore.

Dil, like the other carbocyanine membrane dyes, such as DiO and DiA (Molecular Probes D-275 and D-291), is lipophilic, and thus following application to a tissue, it readily and preferentially diffuses into cell membranes rather than remaining in and diffusing through the aqueous extracellular spaces. 

It is important to know how adriamycin enters cells in order to incorporate the appropriate structural features in designing analogues of this drug. The current theory is that adriamycin and daunomycin passively diffuse into cells but can... 

One (ll) of a number of 2,4-diaminoquinazolines that inhibit dihy-drofolic reductase has a particularly high therapeutic index against L1210 leukemia in mice and is a candidate for clinical trials. Because of difficulties encountered with the transport of active-site-directed irreversible inhibitors (such as III) of dihydrofolic reductase, the emphasis in this study has been shifted to the development of compounds that retain their specificity, but that are better able to passively diffuse into cells. 

---