Question

1. Metblastine, a drug that inhibits microtubule function, is used to treat some forms of cancer. Hypothesize what cellular processes would be affected in cancer cells that are given Metblastine.
2. A mutation in the occludin gene, a tight junction protein, results in severe impairment of intestinal function, resulting in malnutrition and immune disorders. Knowing what you do about the function of tight junctions from class, propose the likely cause of the above disorders (think leaky small intestines). How might the loss of tight junctions impact the selective permeability of the intestinal cells?
3. For a protein to be an integral membrane protein, it would have to be amphipathic, with at least one hydrophobic region. Explain how a protein such as an aquaporin would interact with the surrounding phospholipid bilayer and the surrounding aqueous environment.
4. Describe the mechanism by which glucose and sodium ions are co-transported from the digestive tract into the intestinal cells of an animal? Assume that the intestinal cells already have intracellular glucose.

Answer 1

Metblastine is a microtubule inhibitor (MTI) that stabilize or destabilize microtubules, thereby suppress microtubule dynamics required for proper function of mitotis and effectively block the cell cycle progression and in apoptosis. Metblastin works by stopping the spreading of cancer cells in to two cells. So it blocks the growth of the cancer. This class of chemotherapy drugs works by direct binding to tubulin which prevents microtubule polymerization or disassembly. Tubulin and microtubules are the main targets of this drug which depolymerize microtubules and destroy mitotic spindles, therefore leaving the dividing cancer cells blocked in mitosis with condensed chromosomes. Depolymerization and shrinkage starts when hydrolysis catches up to the tip of the microtubule. This switch from growth to shrinking is called a catastrophe.

Tight junctions are multiprotein junctional complexes, which prevent leakage of fluid across a layer of epithelial cells. They consist of a network of claudins and other proteins. Tight junctions present in different types of epithelia are selective for solutes of differing size, charge and polarity. Tight junctions perform two vital functions: They limit the passage of molecules and ions through the space between cells and block the movement of integral membrane proteins between the apical and basolateral surfaces of the cell.

The OCLN gene encodes occludin, an integral component of tight junctions. A mutation in the occludin gene, a tight junction protein, results in severe impairment of intestinal function, resulting in malnutrition and immune disorders. The tight junction forms an intercellular barrier between epithelial cells within the gastrointestinal tract and liver. Tight junctions maintain the physicochemical separation of tissue compartments by limiting the movement of water and solutes through the intercellular space. So any dysfunction in tight junction has been linked to a variety of local and systemic diseases. In fact, tight junction dysfunction is common in multiple autoimmune diseases. Malnutrition is associated with impaired gut-barrier function.

Tight junctions controls the passage of ions and molecules through the space between cells. Most of the materials must actually enter in to the intestinal cells by diffusion or active transport in order to pass through the tissue. So they block the movement of integral membrane proteins between the apical and basolateral surfaces of the cell. Thus receptor-mediated endocytosis at the apical surface and exocytosis at the basolateral surface can be preserved