Eukaryotic cells contain various organelles surrounded by membranes composed of lipids and proteins. Phospholipids are amphipathic molecules that form the bilayer structure of biomembranes. Their hydrophobic fatty acid tails are located on the interior of the membrane and their polar head groups are on the membrane surface. The unsaturated fatty acids bound to phospholipids contribute to the fluid state of the membrane. Cholesterol interacts with phospholipids and maintains the fluidity of the membrane. Peripheral membrane proteins bind to the membrane surface and integral membrane proteins are embedded in the bilayer. Transporter proteins, an example of the latter, have membrane-spanning domains. Biomembranes not only act as permeability barriers and mediators of ion and metabolite flux, but also have important roles in other cellular processes such as cellular recognition and signal transduction.
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Most of the permeability properties of the membrane are determined by transport proteins. Facilitated diffusion is catalyzed by transporters that permit the movement of ions and molecules down concentration gradients, whereas uphill or active transport requires energy. Primary active transport is catalyzed by pump ATPases that use energy produced by ATP hydrolysis. Secondary active transport uses electrochemical gradients of Na+ and H+, or membrane potential produced by primary active transport processes. Uniport, symport, and antiport are examples of secondary active transport. Protein-mediated transport is a saturable process with high substrate specificity.
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Numerous substrates such as ions, nutrients, small organic molecules including drugs and peptides, and proteins are transported by various transporters. All of these transporters are indispensable for homeostasis. The expression of unique sets of transporters is important for specific cell functions such as muscle contraction, nutrient and ion absorption by intestinal epithelial cells and resorption by kidney cells, and secretion of acid from gastric parietal cells.
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- Describe the similarities between the kinetics of enzyme action and transport processes. Compare the properties of various glucose transporters with those of hexokinase and glucokinase, both kinetically and in terms of physiological function.
- Identify a number of transport inhibitors used in clinical medicine, e.g. Ca++-channel blockers, laxatives and inhibitors of gastric acid secretion.
- Investigate the process of glucose transport across the blood-brain barrier and explain the pathogenesis of hypoglycemic coma.
- Study the role and specificity of ABC transporter in multidrug resistance to chemotherapeutic agents.
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