Peripheral protein diffusion

The fluid-mosaic model for biological membranes as envisioned by Singer and Nicolson. Integral membrane proteins are embedded in the lipid bilayer peripheral proteins are attached more loosely to protruding regions of the integral proteins. The proteins are free to diffuse laterally or to rotate about an axis perpendicular to the plane of the membrane. For further information, see S. J. Singer and G. L. Nicolson, The fluid mosaic model of the structure of cell membranes, Science 175 720, 1972. 

The cytoskeletons of other eukaryotic cells typically include both microtubules and microfilaments, which consist of long, chainlike oligomers of the proteins tubulin and actin, respectively. Bundles of microfilaments often lie just underneath the plasma membrane (fig. 17.22). They participate in processes that require changes in the shape of the cell, such as locomotion and phagocytosis. In some cells, cytoskeletal microfilaments appear to be linked indirectly through the plasma membrane to peripheral proteins on the outer surface of the cell (fig. 17.23). Among the cell surface proteins connected to this network is fibronectin, a glycoprotein believed to play a role in cell-cell interactions. The lateral diffusion of fibronectin is at least 5,000 times slower than that of freely diffusible membrane proteins. 

Statements (c) and (d) are correct Transverse diffusion is only rarely observed [statement (b)], and the term mosaic reier% to the pattern of distribution of proteins in the lipid bUayer [statement (e)]. Peripheral proteins are also considered part of the membrane [statement (a) ]. 

The difference in diffusion rates is due primarily to the difference in mass between phospholipids, which have a molecular weight of approximately 800, and proteins, which have a molecular weight greater than 10,000. In addition, integral membrane proteins may associate with peripheral proteins, which would further decrease their lateral diffusion. 

Strongly with the non-polar part of the lipid bilayer. The peripheral proteins are linked to the precedent by hydrogen bonds. Their location is asymmetrical, at either the inner or the outer side of the plasmic membrane. The molecules of proteins and membrane lipids, constantly in lateral movement, are capable of rapidly diffusing in the membrane. 

In a series of studies, Dubovsky et al. ( 34) measured intracellular calcium ion concentrations in bipolar manic and depressed patients. They found decreases in mean concentrations in four bipolar, manic, and five bipolar, depressed, patients, in comparison with seven normothymic subjects without personal or first-degree relative histories of psychiatric disorders. Their findings were consistent with a diffuse abnormality in the mechanisms modulating intracellular calcium homeostasis. Further, this phenomenon s presence in both platelets and lymphocytes lends credence to a disruption in the cell membrane, the G-protein, or other mechanisms involved in the homeostasis of intracellular calcium ion concentrations. This may also support an extension of their findings from peripheral to neuronal tissue. 

For drugs deposited in the proximity of the peripheral capillary beds of muscle and subcutaneous tissue, lipid solubility is considerably less important than the oral route since even ionized forms of drugs are absorbed with relative ease. The capillary wall in these areas is of sufficient porosity that even drugs with molecular weights as great as 60,000 daltons may be absorbed by passive diffusion. This explains why a protein, such as insulin (5808 daltons), can be given subcutaneously and is absorbed into the bloodstream. 

Once the various steroids have been formed in paticular subcellular compartments, they must be released into the peripheral blood circulation. There is evidence that some steroids are released by passive diffusion, as in the case of corticosterone, but for 18-hydroxylated corticosteroids, Na+/K+-ATPase activity is necessary [6,109]. The situation is more complicated, however, because the presence of proteins in the adrenal cortex, which act as non-classical receptors, may bind C2i steroids to different extents, thus reducing rates of steroid release (see Ref. 6). So far as pregnenolone is concerned, there is no barrier to its efflux from the mitochondria where it is formed from cholesterol [50], During incubation of rat testis [110], pregnenolone was found to travel from the mitochondria, through the ER and cytosol and then out into the medium. The release with time could be resolved into two components, one rapid and the second, much slower. More than 25% of the pregnenolone remained in the tissue after 150 min. incubation. This two-phase release may reflect the presence of two pools of steroid, the initial loss representing passive dif-... 

As outlined in Chapters 23 and 24, water molecules are only loosely bound by hydrogen bonding at the peripheral atoms of the proteins and nucleic acids. Consequently, they are even more mobile than the atoms of the macromolecules to which they are coordinated. As we know from H2O/D2O exchange experiments, some water of hydration molecules are fully and easily replaced even in the crystalline state. The rate of dissociation must be diffusion-controlled and therefore at least in the ns time range. 

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