Macromolecules, cellular transport

Actin and tubulin are two important cellular components that are involved in cell shape and movement. Actin is present in all mammalian cells and is involved in cellular transport and phagocytosis (eating of extracellular materials), provides rigidity to cell membranes, and when bonded to tropomyosin and troponin, forms the thin filaments of muscle. Thbulin is the subunit from which microtubules are self-assembled. Microtubules are most commonly known for their role in cell division. The mechanisms of self-assembly of these macromolecules have been well studied and are important models of biological assembly processes. Below we examine each of these processes. 

One approach to increase cellular transport of macromolecules and then-complexes is to make the species more hydrophobic. For example, point modification of water-soluble proteins with fatty acid residues was used successfully to render these proteins membrane-active and to enhance delivery of these proteins into a cell This approach has been... 

The entry of CL into cells may be essential for the cellular entry [232] or secretion [233] of some macromolecules such as diphtheria toxin and modeccin. Sandvig and Olsnes [232] studied the entry of diphtheria toxin and modeccin into Vero cells in pH 7.2 media containing 20 mM Hepes, 1 mM Ca(OH)2, 5 mM glucose,a sufficient amount of mannitol to ensure isotonicity, and varying concentrations of NaCl. The cellular uptake of 0.1 nM diphtheria toxin at the end of 50 min was strongly dependent on CL concentration. It was 0% at 0 mM NaCl, 25% of the 140 mM NaCl control at 2 mM NaCl, and 60% of the control at 70 mM NaCl. A similar trend was observed for modeccin, i.e., no transport at 0 mM NaCl, 20% of control at 0.05 mM NaCl, 60% of control at 0.1 mM NaCl, 80% of control at 0.5 mM NaCl, and 100% of control at 2 mM NaCl. 

Olsnes, S. (1978) Binding, entry, and action of abrin, ricin, and modeccin. In Transport of Macromolecules in Cellular Systems (S.C. Silverstein, ed.), pp. 103-116. Dahlem Konferenzen, Berlin. 

Figure 4.6 Likely mechanisms by which macromolecules cross cellular barriers in order to reach the bloodstream from (in this case) the lung. Transcytosis entails direct uptake of the macromolecule at one surface via endocytosis, travel of the endosome vesicle across the cell, with subsequent release on the opposite cell face via exocytosis. Paracellular transport entails the passage of the macromolecules through leaky tight junctions found between some cells...

Biomineralization. The processes controlling biomineralization are summarized in Fig. 6.1c. Organized biopolymers at the sites of mineralization are essential to these processes. In unicellular organisms these macromolecules act primarily as spatial boundaries through which ions are selectively transported to produce localized supersaturation within discrete cellular compartments. In many instances, particularity in organisms such as the diatoms that deposit shells of amorphous silica, the final shape of the mineral appears to be dictated by the ultrastrucure of the membrane-bound compartment. Thus, a diversity of mineral shapes can be biologi-... 

At the cellular level, plant secondary metabolites have five major effects on herbivores (a) alteration of DNA replication, RNA transcription, and protein synthesis (b) alteration of membrane transport processes (c) enzyme inhibition and activation (d) blocking of receptor sites for endogenous chemical transmitters and (e) affecting the conformation of other macromolecules (Robinson, 1979). 

The mechanism of benzene-induced toxicity appears to involve the concerted action of several benzene metabolites. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and opened-ring products that are transported to the bone marrow, where secondary metabolism occurs. Metabolites may induce toxicity both by covalent binding to cellular macromolecules and by inducing oxidative damage. Metabolites may also inhibit stromal cells, which are necessary to support growth of differentiating and maturing marrow cells. ... 

SW CNT functionalized with DNA showed a 10 times more effective penetration and expression of genes in vitro, in comparison with molecular DNA. Other charged macromolecules such as polypeptides and liposomes, can provide more effective transport, but they can cause destabilization of the cellular membrane exhibiting a cytotoxic effect. Whereas, using nanotubes for gene delivery has not caused any cytotoxic effects. 

Proteins are the most abundant of cellular components. They include enzymes, antibodies, hormones, transport molecules, and even components for the cytoskeleton of the cell itself. Proteins are also informational macromolecules, the ultimate heirs of the genetic information encoded in the sequence of nucleotide bases within the chromosomes. Structurally and functionally, they are the most diverse and dynamic of molecules and play key roles in nearly every biological process. Proteins are complex macromolecules with exquisite specificity each is a specialized player in the orchestrated activity of the cell. Together they tear down... 

Cellular internalization of macromolecules by endocytosis is an important biological process for their transcellular transport. Endocytosis can be categorized into adsorptive and receptor-mediated endocytosis (RME). RME involves specific binding of ligand to the receptor on the apical cell... 

Even if membranous vesicles were commonplace on the early Earth and had sufficient permeability to permit nutrient transport to occur, these structures would be virtually impermeable to larger polymeric molecules that were necessarily incorporated into molecular systems on the pathway to cellular life. The encapsulation of macromolecules in lipid vesicles has been demonstrated by hydration-dehydration cycles that simulate an evaporating lagoon [53] or by freeze-thaw cycles [54]. Molecules as large as DNA can be captured by such processes. For instance, when a dispersion of DNA and fatty acid vesicles is dried, the vesicles fuse to form a multilamellar sandwich structure with... 

A variation on the whole-cell biotransformation theme is the use of permeabilized cells. Whole cells can be rendered permeable to small molecules yet remain essentially intact by contacting them for a short time with low concentrations of solvents. This process has the effect of making holes in the cellular membrane while leaving enough of the cell membrane and cell wall intact to still contain the enzymes and other macromolecules. The permeabilized cells can then be treated much like immobilized enzymes. This technique is especially useful when transport issues are found to be limiting the reaction. 

ATP plays a central role in cellular maintenance both as a chemical for biosynthesis of macromolecules and as the major soirrce of energy for all cellular metabolism. ATP is utilized in numerous biochemical reactions including the eitric acid cycle, fatty acid oxidation, gluconeogenesis, glycolysis, and pyruvate dehydrogenase. ATP also drives ion transporters sueh as Ca -ATPase in the endoplasmic reticulum and plasma membranes, H+-ATPase in the lysosomal membrane, and Na+/K+-ATPase in the plasma membrane. Chemieal energy (30.5 kJ/mol) is released by the hydrolysis of ATP to adenosine diphosphate (ADP). 

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