I'm having an exam coming up this Thursday, but this will practically pertain to the rest of the semester as well. In particular, I'm having a hard time remembering the biochemistry of why certain things happen the way they do. Any pneumonics for such a thing? I can't seem to remember the chemistry of the different types of collagen, the linker proteins, and practically everything else. According to my professor, he says do not memorize. I think that's bull, considering he expects you to casually know this stuff by now. Here's a sample exam from the past years. HISTOLOGY EXAM I2002Name 1. (13 points) There is a hypothetical mouse that has a serious problem with its skin. The epidermis is very weak and cannot withstand abrasion or stretching – it rips and tears when stressed. When the epidermal epithelium of this mouse’s skin was examined by EM, the following characteristics were noted: •The epithelium looks like that of a normal mouse and is composed of multiple layers of quite flat cells. •The intercellular space in this epithelium is ~20-30nm. The PMs of adjacent cells of the strange mouse exhibit thin, dark, electron dense spots along the inner edge of each cell and very close to the PM. The spots of one cell are juxtaposed directly across the intercellular space from the spots of neighboring cells. On the cytosolic side of these spots a large number of dark filaments of about 10nm diameter can be discerned but there is no obvious pattern to them. •Normal mouse cells exhibit the same spots as described above but the 10nm filaments appear to enter and leave the dark spots. Why does this sick mouse have such weak skin? What’s wrong with it and how is it different from normal? Describe the molecular structure(s) that you think could be responsible for this unusual situation and compare it/them to structures found in normal mouse skin cells. 2. (13 points). The cells of a particular simple columnar epithelium of normal mice engage in synthesis and secretion of a proteoglycan. This PG is continuously secreted across the cells' apical PM by fusion of secretory vesicles of the bulk flow (default) path. It is secreted only at the apical PM. A mutant mouse has been constructed in which the cells of this epithelium still synthesize and secrete the same PG, but they release it at all PM domains, basal and lateral as well as apical. Assume that the mutation has obliterated the function of ONLY ONE protein. What is the function of this protein? Explain and defend your hypothesis. 3. (10 points) Consider a piece of hyaline cartilage the same size as a stratified squamous epithelium in an adult mammal. Even though both tissues are avascular, the epithelial cells will almost invariably be considerably more active metabolically than the chondrocytes. Why do the cells of these two avascular tissues have such widely different levels of metabolic activity? How can the nature of the two tissues account for the difference? 4. (11 points) Osteoclasts are large cells responsible for destroying bone matrix. When actively destroying matrix they look quite different from the way they look when they are quietly waiting for a signal to become active. Describe how you think the ultrastructure of a quiescent osteoclast would change after it is stimulated to start destroying bone. “Ultrastructure” means what you could see in an electron microscope. I know you don’t know what a quiescent osteoclast looks like, so make it up. Each multiple choice question has one correct answer and is worth 3 points 5. Which of the following is most likely to be a useful function of lipid domains in a cell’s plasma membrane (PM)? A lipid domain is a region of a membrane in which the lipid composition is different from the rest of the membrane. 1.Lipid domains can allow particular proteins to associate with and become attached to the membrane. 2.Domains allow direct anchorage of cytoskeleton components to the PM. 3.PM lipid domains allow cells to adhere to each other by way of lipid-lipid interactions. 4.None of the above but one thing which IS true is: 6. The “true” answer to this question is not really known with any certainty, but what is the likeliest reason that proteins that carry out functions in the Golgi apparatus remain in the Golgi? 1.Proteins in the Golgi arrive from the RER and stay there because they would be inactive in any other location. 2.Golgi-specific proteins contain a signal sequence of amino acids that is the ligand for an IMP receptor. The receptor assures they are returned to the Golgi if they should go anywhere else. 3.Golgi proteins have binding affinity for Golgi IMPs that are in turn attached to cytoskeletal elements. 4.Golgi proteins that leave the Golgi are destroyed in lysosomes, making it appear as if all active proteins are actually in the Golgi. 7. What feature determines which proteins pass through the RER translocon and which remain in the cytosol after their synthesis? 1.Proteins composed of predominantly hydrophobic amino acids pass through the RER membrane and translocon, hydrophilic ones remain in the cytosol. 2.Translocon-traversing proteins are specifically attached to the translocon by other proteins. 3.Secretory proteins pass through the translocon. 4.Proteins made predominantly of -helical motifs pass through the translocon. 8. Many cells carry out receptor-mediated endocytosis (RME). It is so common one would think RME offers a benefit to cells and organisms. What might one of those benefits be? 1.The organism benefits because RME gets rid of unwanted or toxic substances. 2.RME allows cells to sample the composition of their environment. 3.RME allows cells to take up molecules that are present at very low concentrations in the extracellular space. 4.RME creates a constant stream of material flowing into cells. 9. During the process of N-linked glycosylation a large oligosaccharide is covalently attached to proteins by a glycosyl transferase enzyme. Where is this enzyme located? 1.In the cytosol associated with actively translating ribosomes. The cytosol is that portion of a cell’s cytoplasm that contains no organelles. 2.Attached to the cytosolic side of the RER membrane. 3.Inside the lumen of the RER. 4.Inside the Golgi lumen. 5.Attached to the cytosolic side of the Golgi membrane. 10. If you were to add radioactive fatty acids to live cells, where in the cells would you expect first to see the radioactivity contained in a molecule significantly larger than the fatty acid you added? 1.SER. 2.RER. 3.Nucleus. 4.Lysosome. 5.Golgi apparatus. 11. During intramembranous bone formation, crystals of calcium-phosphate form on cross-striated collagen fibers, but identical collagen fibers in non-bone-forming dense irregular connective tissue (DICT) do not support crystal formation. Which is the likeliest reason for this difference? 1.The collagen ‘hole zone’ is prevented from nucleating crystals by interference from matrix proteoglycans. 2.Proteins secreted only from bone-forming cells (osteoblasts) nucleate crystals on collagen fibers. 3.Minute calcium phosphate crystals found free in blood and in the aqueous part of the connective tissue membrane, the one forming the bone, are bound to collagen fibers by a specific crystal-binding protein. 4.Fibroblasts of non-bone-forming DICT slowly secrete protons into the extracellular space to dissolve crystals that spontaneously form in the DICT. 5.None of the above, but one likely reason is: 12. Ribosomes are often seen attached to the outer nuclear envelope membrane. What are they most likely doing? 1.Translating an mRNA and inserting nuclear envelope IMPs into the membrane. 2.Synthesizing the nuclear pore proteins. 3.Synthesizing the same sorts of proteins that are made by ribosomes attached to the RER. 4.Creating channels for the movement of proteins into and out of the nuclear lumen. 13. What is a difference between proteins found in the nuclear lumen and proteins found in the Golgi apparatus? 1.When first synthesized, the two types have domains in their 30 structures that are recognized by different binding proteins. 2.Nuclear proteins are less hydrophobic than Golgi proteins. 3.Nuclear proteins may be glycosylated; Golgi proteins are not. 4.Nuclear proteins remain within the nucleus; Golgi proteins are in transit to somewhere else. 14. Which of the following accurately describes elastic fibers of connective tissue proper? 1.Congregations of the protein elastin are surrounded by fibrils. 2.Elastin polymerizes to form the fibrils which associate with each other to form the elastic fibers. 3.Thin collagen fibers are cross-linked by elastin. 4.A cylindrical core of proteoglycan is surrounded by elastin fibrils. 5.Fenestrated (interrupted) sheets of cross-linked elastin self-associate to form fibers. 15. Which of the following pairs of cellular activities is most likely to involve the same molecular mechanism? That is, both activities in one of the examples below are driven by the same process. 1.An epithelial cell endocytoses an LDL particle (low-density lipoprotein) and a macrophage phagocytizes a bacterium. 2.A respiratory epithelial cell waves its cilia back and forth and a cell moves through connective tissue. 3.Nutrient molecules move along osteocyte canaliculi and vesicles move along neuron axons. 4.Capillary endothelial cells respond to vasodilators (increase capillary permeability) and smooth muscle cells contract. 16. For reasons of your own, probably having to do with intestinal absorption, you want to inactivate a mouse gene (a knockout) so that the microvilli of intestinal columnar cells don’t “stand up” the way they do in a normal brush border. To achieve this phenotype, which of the following genes would you NOT try to knock out? 1.Vinculin, a protein that links microfilaments to the IMP integrin. 2.TW 260. 3.The cadherin uvomorulin. 4.The catenin that binds to uvomorulin. 5.None of the above but a gene that would make them lie down is 17. The very large proteoglycan aggrecan, found at high concentration in cartilage, is composed of several different macromolecules. Where is this complex molecule assembled into its final form? 1.The RER. 2.Cis-, medial-, or trans-Golgi. 3.Trans-Golgi network. 4.Secretory vesicles. 5.Outside the cell. 18. Most consider osteoid, the thin layer of immature bone found under active osteoblasts, to contain all the components of true bone matrix but that one or more of these components is in an ‘immature’ form. Which of the following components do you think is likely to be the one that delays true bone matrix formation? 1.Proteoglycans. 2.Type I collagen. 3.Calcium phosphate crystals. 4.Bone sialoprotein. 5.Osteopontin. Why did you pick your answer in the above question? You could justify a “wrong” answer. If you’re sure of your answer you don’t need to justify it. 19. Which of the following would you expect to reduce the rate at which a large (200nm diameter), glycosylated, globular protein leaves the lumen of a continuous capillary and enters connective tissue but would NOT reduce the rate at which it leaves a discontinuous capillary (sinusoid). 1.Lowered blood pressure. 2.Increased concentration of cholesterol in the endothelial cells’ PMs. 3.More interrupted belt tight junctions. 4.Destruction of endothelial basal lamina. 20. SLIDE SHOW. Each of the 4 slides is worth 2 points. 1. 2. 3. 4. So far, my problems spots are what the hell trabeculae is (I kid you not, none of my cell or histo books have that defined clearly). Question 16 has been bugging the crap out of me, and my textbooks indicate nothing of the normal cell-to-cell junctions that would apply in that case. We debated about it for a while, and we think it's A because of the existance of actin microfilments that's prevalent in Microvillus. But we're not given the exam key (our professor seems to get offended when we ask him about that), so we have no fucking clue if we're "logically" arriving at the correct conclusion.