Cell, membrane acid accumulation

Increased acid tolerance correlates strongly with a decrease in proton accumulation in the cytoplasm. This altered proton permeability is again associated with changes in the protein composition of the cell membranes. Acid-adapted E. coli changes the lipid composition of its membranes, and elevated levels of cyclopropane fatty acids are often found. This may mean that changes in the protein composition of the cell membrane are a result of changes in the membrane lipid composition. Both lipid and protein alterations may be necessary to protect a bacterial cell in acidic environments (Jordan, Oxford, and O Byrne, 1999). 

Mercury is known to exert an effect on the synthesis of membrane lipids. Mercuric chloride produces lipid alteration in pig kidney epithelial cells (LLC-PK, cells), with rapid accumulation of unesterified fatty acids (particularly arachidonic acid) and lysophospholipids and loss of cellular phospholipids... 

The first experiments implicating a role for PLD activity in neutrophil function were performed by Cockcroft and colleagues (Cockcroft Stutchfield, 1989 Cockcroft, 1992) who measured phosphatidic acid accumulation in cells whose membrane phospholipids or ATP were radiolabelled. These experiments showed that phosphatidic acid accumulation during cell activation did not derive from DAG, but rather was directly generated from a phospholipid. Phosphatidic acid production from DAG (generated by PLC)... 

The polymyxins are polypeptide antibiotics that contain both hydrophilic and lipophilic regions. These antibiotics accumulate in the cell membrane and probably interact with membrane phospholipids. Most likely the fatty acid portion of the antibiotic penetrates the hydrophobic portion of the membrane phospholipid and the polypeptide ring binds to the exposed phosphate... 

Sialic acid seems to be involved not only in regulation of the lifetime of soluble, serum glycoproteins but also of mammalian blood-cells. It was observed by Woodruff and Gesner474 that desialylated lymphocytes are reversibly trapped in liver they recirculate to the blood stream after about 24 h. This phenomenon was confinned with Listeria-specific, mouse T lymphocytes, which accumulated in the liver for one day, in contrast to the control cells.60 Reappearance of these cells in the circulation after one day may be explained by re-sialylation of their membrane glycoconjugates. This time period is in the range observed for the turnover of sialic acid in cell membranes, lasting, for example, for 33 h in rat-liver hepatocytes.475... 

Vitamin B1 is required in humans for two essential enzymatic reactions Ihe synthesis of methionine and the isomerization of methylmalonyl CcA that is produced during the degradation of some amino acids, and fatly acids with odd numbers of carbon atoms (Figure 28.5). When the vitamin is deficient, abnormal fatty acids accumulate and become incorporated into cell membranes, including those of the nervous system. This may account for some of the neurologic manifestations of vitamin P12 deficiency. 

Assembly and release. The assembly of the capsid and its association with nucleic acid is then followed by release of the virus front the cell. This may occur in different ways, depending upon the nature of the virus. Naked viruses may be released slowly and extruded without cell lysis, or released rapidly by disruption of the cell membrane. DNA viruses, which mature in the nucleus, tend to accumulate within infected cells over a long period. Enveloped viruses generally acquire their envelope and leave the cell by budding through the nuclear or cytoplasmic membrane at a point where virus-specified proteins have been inserted. The budding process is compatible with cell survival. 

Phase I and II clinical trials indicated that acronycine reduced pain of the spine in some patients with multiple myeloma [280,282,283]. Acronycine has been reported to cause leukopoenia and to have CNS-depressant activity [284], Biochemically, acronycine inhibits incorporation of extracellular nucleosides into the RNA and DNA of leukaemia L-5178Y cell culture. There is, however, no evidence of interaction between acronycine and DNA or inhibition of template activity of DNA. This alkaloid does not inhibit nucleic acid synthesis in the cell, but rather inhibits the accumulation of extracellular uridine or thymidine, as nucleotides, in the intracellular precursor pool [285, 286], Acronycine, acting primarily on membranous organelles [287], seems to interfere with the structure, function and/or turnover of cell membrane components, thereby changing the fluidity of the plasma membrane [288]. 

Cholesterol is a vital component of the human body. It stabilizes cell membranes and is the precursor of bile acids, vitamin D, and steroid hormones. The body s cells can synthesize cholesterol when needed, but excess cholesterol cannot be broken down and must be excreted from the body through the bile into the small intestine. When imbalances occur, cholesterol can accumulate in the gallbladder promoting gallstone formation. Cholesterol accumulation in the bloodstream (hypercholesterolemia) can cause atherosclerotic plaques to form within artery walls. 

Among other actions, hormones are known to modify the activities of membrane ion transporters and ion channels, affect the membrane potential, and modulate Na+-driven substrate transport (for review see Moule and McGivan, 1990). These actions in turn are expected to modify cell volume. Thus, for example, hormones are now recognized as potent modulators of liver cell volume (Haussinger and Lang, 1992). Whereas anisoosmotic exposure and amino acid accumulation in hepatocytes primarily lead to cell swelling with secondary activation of volume-regulatory ion transporters, hormones primarily affect the activity of these volume-... 

The uptake and accumulation of various amino acids in Lactobacillus arabinosus have been described. Deficiencies of vitamin B6, biotin, and pantothenic acid markedly alter the operation of these transport systems. Accumulation capacity is decreased most severely by a vitamin B6 deficiency. This effect appears to arise indirectly from the synthesis of abnormal cell wall which renders the transport systems unusually sensitive to osmotic factors. Kinetic and osmotic experiments also exclude biotin and pantothenate from direct catalytic involvement in the transport process. Like vitamin B6, they affect uptake indirectly, probably through the metabolism of a structural cell component. The evidence presented supports a concept of pool formation in which free amino acids accumulate in the cell through the intervention of membrane-localized transport catalysts. 

Therefore, the three vitamin deficiencies so far studied in detail appear to affect amino acid transport and accumulation in similar but indirect ways. The accumulation defect is most pronounced in vitamin B6-deficient cells, for which there is also strong evidence implicating an abnormality in cell wall composition as a likely source of the change in transport activity. Direct evidence for a cell wall change in biotin- and pantothenate-deficient cells has not yet been obtained. The possibility remains, therefore, that the change in accumulation activity may be caused by an abnormality in some other structural component such as the peripheral cell membrane. 

Further support comes from the studies relating cell wall biosynthesis and amino acid accumulation capacity in vitamin B6-deficient cells, since it is difficult to account for these observations without attributing considerable osmotic activity to the accumulated amino acids. Any description of accumulation which invokes amino acid attachment to intracellular binding sites, whose affinity can be reduced by a vitamin B6 deficiency, must account for the stimulation of uptake that accompanies the synthesis of essentially extracellular cell wall material. If the reduction in affinity occurs because the cell interior becomes overhydrated (a reasonable postulate which follows from the osmotic experiments), the beneficial effect of wall synthesis is not readily explicable, since vitamin B6-deficient cells have a swollen appearance which is not significantly altered after wall synthesis has been stimulated. Thus, the existing overhydration within the cell probably is not reversed by this change. In contrast, the deposition of additional wall substance would prevent further unfavorable consequences of swelling such as membrane distention, and, in this way, forestall the premature cessation of amino acid accumulation. 

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