2019 Midterm III Unannotated Biology/Chemistry Exam PDF

1. Osmotic diuretics are molecules derived from monosaccharides. Select the FALSE statement that accurately characterize them. Finish the sentence. Osmotic diuretics… A. are administered by intravenous injection. B. can be used to reduce intracranial pressure....

1. Osmotic diuretics are molecules derived from monosaccharides. Select the FALSE statement that accurately characterize them. Finish the sentence. Osmotic diuretics… A. are administered by intravenous injection. B. can be used to reduce intracranial pressure. C. can be used to reduce intraocular pressure. D. Can be administered orally. E. are used to shrink endothelial cells and expand tight junctions between the cells for more efficient drug delivery 2. Monosaccharide-derived polyols, but not the original natural monosaccharides, found numerous applications in pharmacy as excipients, humectants, sweeteners, osmotic diuretics, and substrates for manufacturing of mild detergents. Among the reasons for this disparity listed below, which is responsible for this difference: A. Polyols derived from monosaccharides have easier bioavailability than the original monosaccharides. B. Monosaccharide-derived polyols are metabolized much more slowly than the original monosaccharides. C. Solutions of polyols are very viscous, therefore can serve as suspending agents, whereas those made form monosaccharides are not. D. In general, polyols are sweeter than the original carbohydrates. E. All cited reasons contribute equally. 3. Sorbitan is a product of sorbitol dehydration and a precursor of SPANS (A) and TWEENS (B) shown below, two different classes of mild detergents, suspending and texturizing agents. These products are characterized by their different propensity to form oil-in-water or water-in-oil dispersions. Identify the single FALSE statement from the choices below: A B A. Compound B has a large polar residue as compared to cross-section of the hydrophobic tail. B. A water-in-oil dispersion is formed by compound A. C. Compound B forms an oil-in-water dispersion. D. In a water-in-oil dispersion, the head group points inside the aggregates, and hydrocarbon tails point outside. E. In the aqueous dispersions of compound A, water phase surrounds the aggregates and the hydrophobic phase is inside the aggregate. W/O Water span 80 Oil 4. Both cellulose and amylose are polymers of glucose, but have starkly different properties. Select the FALSE statement: A. Cellulose is poly-b(1-4)-linked glucosyl glucose. B. Amylose, also known as a component of starch, is poly-a(1-4)-linked glucosyl glucose. C. Amylose can be readily metabolized by beta-amylase. D. Cows and horses can feed on cellulose-containing pastures since organisms of ruminants express an enzyme cellulase. E. Cellulose forms linear fibers, whereas amylose adopts a structure of a helix. 5. Cellulose has found numerous applications in pharmacy both as a natural polymer, but also in a form of its multiple chemical derivatives. Select the FALSE statement that rationalizes the specific uses of cellulose and its derivatives. O CH3 ONa Me O O O O HO HO RO O O O O O O n n n OMe OH O 1 2 3 O COOH A. Microcrystalline cellulose serves an excipient in tablet compounding that helps to facilitate tablet disintegration due to weakening of hydrogen bonding interactions between microcrystals in aqueous environment. B. Unlike cellulose, methyl cellulose (1) is dispersible in water due to removal of some of the hydrogen bonding interactions that stabilize the solid form of cellulose. C. Sodium carboxymethyl cellulose (2) is soluble in water due to the presence of negative charges. D. Cellulose acetate phthalate (3) is used for enteric coating of certain tablets since it is soluble in the low-pH environment of human upper GI tract. E. Methyl cellulose (1) forms very thick dispersions, and is used in formulation of suspensions of solid drugs. 6. Galectins are a type of lectins – carbohydrate binding proteins, with specificity for ligands that contain b-galactoside at the terminus of their structures. The galactose-containing ligands are located on the surface of certain protozoan parasites and constitute a way of anchoring to human cells displaying galectins on their surface. Such interactions can be disrupted by synthetic galactose- containing ligands. Among the structures shown below, which could potentially be used to disrupt such an anchoring process. OH OH OH OH OH HO HO OH HO O HO O O O O O OH HO HO HO HO O HO HO HO OH HO HO HO OR OR OR HO OR OH A B C D E R = carbohydrate residue 7. Potency of monosaccharide binding with proteins is usually weak, but oligosaccharide binding to lectins is stronger with binding constants below micromolar. Select the FALSE statement. Rationalize both observations: A. Binding of monosaccharides to proteins results in relatively small net enthalpic change. B. Much of the overall Gibbs energy of binding is due to entropy gain by the water molecules being displaced from the binding site by the monosaccharide ligand. C. Binding of a larger ligand, such as oligosaccharide, in a larger binding site, results in displacement of more numerous water molecules, resulting in greater entropy gain. D. Oligosaccharides are relatively rigid structures (presence of rings), hence binding such preorganized ligand results in a small entropy loss. E. None, all statements are true. 8. The most apparent property of mono- and di-saccharides is their ability to elicit a sweet taste. Choose two FALSE statements regarding this mechanism. A. Sweet taste sensation appears in response to stimulation of GPCR-type receptors, T1R2 and T1R3. B. T1R receptors specifically recognize only those molecules that are structurally related to carbohydrates. C. The natural carbohydrates are strongest binders at these receptors. D. Ligands of T1R receptors that also bind to other proteins may display bitter aftertaste. E. Discovery of some artificial sweeteners was serendipitous. 9. Fructose is a ketohexose, that is an ingredient of bee honey and industrial sweetener, high fructose corn syrup (HFCS). Choose the FALSE characterizations of fructose: A. Fructose can isomerize to glucose vial an enol form. B. Fructose exists as an equilibrium mixture of furanose and pyranose cyclic forms. C. The furanose form of fructose is more stable and sweeter than pyranose. D. The equilibrium between furanose and pyranose shifts to furanose at higher temperatures. E. HFCS is not used to sweeten hot drinks. 10. Unfavorable properties of certain drugs, such as low metabolic stability, bitter taste, and liquid physical form, can be improved/changed by their formulations as inclusion complexes with cyclodextrins. Based on the knowledge of the type of interactions needed to form such complexes, which of the following drugs COULD NOT be formulated in this manner (CHOOSE TWO). A. Misprostol B. Diclofenac C. Pioglitazone D. Metformin E. Vigabatrin 11. Netropsin, a polyamide endowed with antibiotic and antiviral activity, is a DNA-binder. Based on its structure shown below, choose the TRUE statement. A. It is a DNA intercalator.  B. It is a minor groove binder. C. It is a major groove binder. D. It is an electrostatic binder. E. It disrupts the formation of the duplex between guanine and cytidine base pairs. 12. Adriamycin, a known chemotherapy drug, is a DNA-interacting agent and a topoisomerase inhibitor. Based on this information and the structure shown below, the mode of its interaction with DNA is (finish the sentence)…. A. intercalation. B. minor groove binding. C. major groove binding. D. electrostatic binding. E. displacement of cytidine by forming three hydrogen bonds with guanine. 13. Oxaliplatin, an anticancer drug, is a DNA modifier. What is the mode of oxaliplatin-DNA interaction and its consequences? Choose TWO FALSE answers. A. It covalently binds to imidazole-type nitrogen of guanine. B. As a divalent agent, it binds to adjacent nucleobases on the same DNA strand. C. As a divalent agent, it forms a crosslink between the opposite strands. D. As a divalent agent it forms a crosslink between the phosphate groups on the same strand. E. The modification disrupts the recognition of the base by RNA polymerase and stalls DNA transcription. 14. Which of the following compounds shown are insufficiently reactive and may require metabolic activation? Choose two. A. Ifosfamide B. Lomustine C. Sulfur mustard D. Thiotepa E. Chlorambucil 15. As compared to nonenzymatic transmembrane receptors, enzymatic proteins are more convenient drug targets because: A. Most have native conformations in cytosol, and hence can be expressed in active state. B. As soluble proteins, their 3D structures can be solved using NMR and crystallographic methods. C. The inhibitor/drug design can start based on the structure of active site. D. Both the efficiency or excess of a metabolite responsible for a given pathology can be remedied by enzyme inhibition. E. All statements are true. 16. Catalysis by two enzymes is characterized by free energy profiles shown below drawn in red (enzyme 1) and blue (enzyme 2). Choose two FALSE statements that characterize the two enzymes. A. Enzyme 2 binds the substrate more tightly than enzyme 1. B. Enzyme 2 binds the product more tightly than enzyme 1. C. The reaction in the direction from S to P is endothermic. D. Enzyme 2 is a more efficient catalysts than enzyme 1. E. Enzyme 2 is significantly inhibited by the product. 17. Angiotensin-converting enzyme (ACE) is inhibited by the drug captopril with Ki = 1.2 nM. In the absence of an angiotensin substrate, what is the approximate active site occupancy at drug concentration 1.2 µM. A. 0.1% B. 1% C. 10% D. 90% E. 99.9% 18. The literature shows, the enzyme HMG-CoA reductase (HMG-CoAR) binds its substrate HMG-CoA with equilibrium constant, KD = 4 µM affinity. An inhibition assay of this enzyme by the drug Fluvastatin was performed at a HMG-CoA concentration = 4 µM, indicated that 50% rate reduction was achieved at the drug concentration IC50 = 28 nM. What is the Ki of Fluvastatin? A. 2.8 nM B. 14 nM C. 28 nM D. 14 nM E. 4 µM 19. In the early 1990s, several research groups were developing an HIV-protease inhibitor for treatment of HIV-AIDS. HIV protease cleaves an amide bond of a long viral polypeptide, cutting it into shorter fragments. Despite approaches from different starting points, most groups have converged on using transition state analog mimicry as the basis for the inhibitor design. The abbreviated mechanism of  HIV protease is shown below. The rate-limiting step k1 forms a hypothetical structure of an intermediate which is close to that of the transition state. The subsequent step k2 is fast. What structural features could be most advantageous to include in a transition state analog inhibitor? Choose two. H Base O H O HO O O k1 k2 R2 R2 R1 H2N R2 R1 N R1 N O H H HOOC intermediate A. Negative charge. B. Tetrahedral geometry of the central reaction site. C. Extended distance between the central carbon atom and the nitrogen. D. Positive charge E. C-C instead of C-N bond. 20. Huperzine A is an alkaloid from Chinese herb Huperzia serrata that displays significant inhibitory potency and selectivity toward acetylcholinesterase (AChE) vs. butyrylcholinesterase (BChE) with corresponding Ki values of 82 nM vs. 74 µM, respectively, a 900-fold selectivity. Selective inhibition of AChE is necessary for treatment of cognitive deficits in dementia. The table below shows the concentration of huperzine A and approximate extent of inhibition of both AChE and BChE. Which of the table entries are correct? Caution: when you pick eg. A as correct, it means B- D are incorrect. [Huperzine] % inhibition of AChE % inhibition of BChE A 82 nM 50 ~0.1 B 0.82 µM ~90 ~1 C 74 µM >99 ~50 D 7.4 µM ~99 ~10 A. A B. B C.C D.D E. All are correct 21. A common architecture of a transmembrane receptor is that of several transmembrane helices connected by the loops. Choose the FALSE characteristics of transmembrane receptor topology. A. Transmembrane helices are built primarily of hydrophobic amino acids. B. The helices are connected by peptide sequences containing primarily hydrophilic amino acids. C. For those transmembrane proteins charged with transport of ions or polar solutes, the helices are arranged in such way that the inner surfaces are lined with more polar side chains. D. Activation of transmembrane receptors occurs by conformational changes effected by loop phosphorylation, rotation of helices or their vertical displacements. E. None, all statements are true. 22. The animation video presented below spanning 5 ns of membrane life-time, shows the overall high fluidity of the phospholipid membrane, but no apparent lateral or transmembrane movements of entire lipid molecules. Choose the FALSE statement. A. Conformational changes about the single C-C bond occur in sub-nanosecond time frame. B. Movement of whole molecules in the plane of the bilayer is slower than the 5 nanosecond time frame of the animation. C. The movement from the outer layer to the inner layer of a membrane occurs within days. D. The movements of fatty acid chains are restricted only by Van der Waals interactions, and not by hydrogen bond or dipolar interactions. E. None, all statements are true. 23. The rate of drugs passive transport through the biological membranes depends on two rate constants: k1 - dissolution in the membrane, and k2 - exit from membrane into the cytosol. Select two TRUE statements. A. Drugs with logD