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1. The effect of H+ on hemoglobin (Bohr effect) is to: A. B. C. D. E. 2. Osteogenesis imperfecta (OI) is a heterogeneous group of diseases in which there is a defect in the synthesis of collagen. Some involve the synthesis of a mutated form of collagen. Which of the following mutations would most likely be a lethal mutation? A. B. C. D. E. 3. Pro → Gly Lys →Gly Gly →Ala near the N-terminus Gly →Asp near the C-terminus Lys →Arg The repeating secondary structures as found in ß-strands, ß-turns, and α-helices are primarily stabilized by: A. B. C. D. E. 4. Stabilize the oxy form Enhance O2 delivery to peripheral tissues Destabilize the deoxy form Oxidize Fe2+ Sterically block the O2 binding sites Hydrogen bonds Disulfide bonds Hydrophobic interactions Van der Waals interactions Ionic interactions If the nucleic acids were isolated and separated from cultured skin fibroblasts, where would inosine most likely be located? A. B. C. D. E. DNA Intron region of hnRNA mature mRNA tRNA rRNA Medical School Biochemistry - Fall 2004 Block I Exam (Version 3- September 21, 2004) FOR EACH OF THE FOLLOWING MULTIPLE CHOICE QUESTIONS CHOOSE THE MOST APPROPRIATE ANSWER 1 5. Which of the enzymes listed below possesses the following properties: recognizes the promoter within the structural gene, catalyzes the polymerization of a small nucleic acid that later on undergoes extensive base modifications, and is insensitive to rifampicin but sensitive to high concentrations of alpha-amanitin. A. B. C. D. E. 6. As part of a summer research project, you are given the task of isolating and purifying an enzyme from porcine kidneys. Which of the following separation techniques would most likely yield the purest active enzyme in a single step? A. B. C. D. E. 7. Eukaryotic RNA polymerase I Eukaryotic RNA polymerase II Eukaryotic RNA polymerase III Prokaryotic RNA polymerase Viral reverse transcriptase Affinity chromatography using a bound competitive inhibitor SDS-polyacrylamide gel electrophresis Ion-exchange chromatography Differential centrifugation Size-exclusion chromatography Complete endonucleolytic digestion of sequences connecting two tandem nucleosomes would produce DNA fragments of size: A. B. C. D. E. 60 by 140 by 200 by 260 by 340 by Medical School Biochemistry - Fall 2004 Block I Exam (Version 3- September 21, 2004) FOR EACH OF THE FOLLOWING MULTIPLE CHOICE QUESTIONS CHOOSE THE MOST APPROPRIATE ANSWER 2 8. Many antibiotics are inhibitors of protein synthesis. Which of the following correctly matches the antibiotic with the mechanism by which it inhibits protein synthesis? A. B. C. D. E. 9. Which of the following is COMMON to myosin of smooth and striated muscle as well as nonmuscle myosin I. A. B. C. D. E. 10. They are regulated by phosphorylation of light chains They have movable lever arms They attach to actin filaments that have troponin and tropomyosin They have a coiled-coil tail They form bipolar thick filaments All of the following are true about all immunoglobulins, EXCEPT: A. B. C. D. E. 11. Chloramphenicol - prevents translocation Erythromycin - prevents formation of the initiation complex Puromycin - causes premature polypeptide chain termination Streptomycin - inhibits binding of aminoacyl-tRNA to the A site Tetracycline - inhibits peptidyltransferase Contain multiple polypeptide chains Contain disulfide bonds Recognize antigens Are synthesized by B cells Contain a hydrophobic, membrane-bound domain Antibody may be used as a probe to screen which of the following gene libraries for identifying a clone carrying the gene of interest A. B. C. D. A genomic library in lamda phage A genomic library in cosmid A genomic library in bacterial artificial chromosome A cDNA library in expression plasmid Medical School Biochemistry - Fall 2004 Block I Exam (Version 3- September 21, 2004) FOR EACH OF THE FOLLOWING MULTIPLE CHOICE QUESTIONS CHOOSE THE MOST APPROPRIATE ANSWER 3 12. Which of the following statements about heme and hemoglobin structure is/are CORRECT: 1. Intersubunit ionic bonds play a critical role in cooperative oxygen binding 2. Binding of the heme to hemoglobin subunits relies on hydrophobic and ionic interactions 3. The iron of free heme has two unoccupied coordination positions 4. The proximal 1Iis (F8) in both the alpha and beta chains participate in coordination of the heme iron A. B. C. D. E. 13. Xeroderma pigmentosum arises due to persistence of: A. B. C. D. E. 14. 1, 2 and 3 only 1 and 3 only 2 and 4 only 4 only All four Chemical indirect mutagenesis Acridine intercalation Inosine incorporation Cytosine deamination Thymidine dimers A point mutation occurs in the gene for the leader peptide of the tryptophan operon of E. coli causing one of the two codons for Trp to be changed to Phe. Which of the following is the most likely outcome of this mutation? A. B. C. D. E. The resultant leader peptide becomes an inhibitor of RNA polymerase The leader peptide acts as a corepressor yielding a repressor-corepressor complex that prevents transcription Transcription and translation of enzymes involved in the synthesis of Trp increase The mutation results in a decreased ability to synthesize Trp when cellular levels of Trp are low The leader peptide inhibits the formation of Trp-mRNAtrp Medical School Biochemistry - Fall 2004 Block I Exam (Version 3- September 21, 2004) FOR EACH OF THE FOLLOWING MULTIPLE CHOICE QUESTIONS CHOOSE THE MOST APPROPRIATE ANSWER 4 15. The synthesis of proteins requires the expenditure of energy in the form of high energy phosphate bonds (ATP or GTP). Which of the following steps in the translation process does not involve the cleavage of a high energy phosphate bond? A. B. C. D. E. 16. Which of the following statements is in agreement with the statement "The genetic code is degenerate, but not ambiguous"? A. B. C. D. E. 17. Formation of aminoacyl tRNAs Formation of the complete initiation complex Bringing an aminoacyl tRNA to the A site Formation of the elongated peptidyl tRNA Moving the peptidyl tRNA from the A site to the P site Many of the tRNAs carry more than one amino acid All triplet codons have at least one uracil Many of the amino acids are specified by more than one codon There are 64 aminoacyl tRNAs Some triplet codons are made up of repeating purines or pyrimidines Which of the following is FALSE with respect to enzyme catalysis? A. B. C. D. E. Zero order reactions are independent of the substrate concentration The Michaelis constant, KM, is a measure of substrate affinity The initial rate of product formation, Vi, depends on enzyme and substrate concentration Noncompetitive inhibitors alter both Vmax and KM The Hill coefficient is a measure of cooperativity Medical School Biochemistry - Fall 2004 Block I Exam (Version 3- September 21, 2004) FOR EACH OF THE FOLLOWING MULTIPLE CHOICE QUESTIONS CHOOSE THE MOST APPROPRIATE ANSWER 5 18. Which of the following statements about vertebrate striated muscle is/are CORRECT: 1. 2. 3. 4. A. B. C. D. E. 19. 1, 2 and 3 only 1 and 3 only 2 and 4 only 4 only All four An RNA fragment containing an adenylate residue linked to three nucleotides by phosphodiester bonds likely resulted from which of the following processes: A. B. C. D. E. 20. ATP binds at the P loop region of myosin A conformational change in myosin involving the relay helix immediately follows ATP hydrolysis Troponin C is the regulatory calcium-binding protein of the thin filament Myosin head groups in relaxed muscle is bound to ADP, Pi, and actin Splicing of Pre-mRNA Polyadenylation Processing of rRNA Intron removal from pre-tRNA 5'-capping Which amino acid residue would be least frequently found on surfaces of globular proteins in aqueous solution? A. Glutamate B. Serine C. Valine D. Glutamine E. Arginine 21. The only RNA molecules that do not require post-transcriptional processing are the: A. B. C. D. E. Euka.ryotic rRNAs Eukaryotic tRNAs Prokaryotic rRNAs Prokaryotic tRNAs Prokaryotic mRNAs Medical School Biochemistry - Fall 2004 Block I Exam (Version 3- September 21, 2004) FOR EACH OF THE FOLLOWING MULTIPLE CHOICE QUESTIONS CHOOSE THE MOST APPROPRIATE ANSWER 6 22. All of the following are TRUE statements about regulation of the expression of eukaryotic genes EXCEPT: A. B. C. D. 23. The antibiotic, ciprofloxacin, is an inhibitor of: A. B. C. D. E. 24. Sliding clamp Helicase DNA ligase Primase Topoisomerase The increased metabolic activity that occurs in muscle tissue during exercise causes hemoglobin to release more oxygen to the tissue for all of the following reasons EXCEPT: A. B. C. D. 25. Alternate splicing of tropomyosin gene transcripts can generate a family of tissuespecific proteins In intestinal cells, the apoprotein B mRNA is modified creating a protein of smaller size than its liver counterpart During the production of antibodies, lymphocytes produce shorter transcripts by using different cleavage and polyadenylation sites. The iron response element (IRE) in the 5' untranslated region of ferritin binds a specific protein that induces translation Muscle produces higher levels of H+ Muscle produces higher levels of CO2 The partial pressure of oxygen in the muscle is reduced BPG dissociates from hemoglobin Which of the following enzyme-inhibitor interactions would yield Lineweaver-Burk plots that had identical intercepts on the 1/Vi axis for the enzyme with and without inhibitor? A. B. C. D. Inhibition of dihydrofolate reductase by the anticancer drug methotrexate Inhibition of bacterial transpeptidase by penicillin Inhibition of acetylcholinesterase by diisopropylfluorophosphate Heterotropic allosteric inhibition of isocitrate dehydrogenase by ATP Medical School Biochemistry - Fall 2004 Block I Exam (Version 3- September 21, 2004) FOR EACH OF THE FOLLOWING MULTIPLE CHOICE QUESTIONS CHOOSE THE MOST APPROPRIATE ANSWER 7 26. Allosteric regulatory enzymes: A. B. C. D. E. 27. All of the following statements accurately describe structural characteristics of collagen EXCEPT: A. B. C. D. E. 28. Tropocollagen has a rod-shaped structure formed from three helical polypeptides Each collagen a-chain is stabilized by intrachain H-bonds The amino acid glycine is present in every third position in the collagen a-chain Sugar residues are bound to collagen through hydroxylysine residues Procollagen contains N- and C-terminal globular regions The Bohr effect involves the side chain of histidine 146 in the beta chain of hemoglobin. Consider a mutation in which histidine 146 is converted to lysine. If the mutation is not lethal, which of the following molecular or physiological phenotypes would most likely be observed? A. B. C. D. E. 29. Possess more than one subunit Are always inhibited by their end product Obey the enzyme kinetics of the Michaelis-Menten equation Have a single binding site for their substrates Remain in their initial conformation A loss of cooperative oxygen binding to the mutated hemoglobin An increase in the pH of peripheral tissues relative to normal levels Polymerization of the mutated deoxyhemoglobin An overall decrease in the affinity of the mutated hemoglobin for oxygen Enhanced oxidation of Fe2+ to Fe3+ Which enzyme has an integral RNA component that acts as a template for DNA synthesis? A. B. C. D. E. Telomerase RNaseP Peptidyl transferase Nucleotidyl transferase Reverse transcriptase Medical School Biochemistry - Fall 2004 Block I Exam (Version 3- September 21, 2004) FOR EACH OF THE FOLLOWING MULTIPLE CHOICE QUESTIONS CHOOSE THE MOST APPROPRIATE ANSWER 8 30. Which of the following is FALSE regarding eukaryotic transcription? A. B. C. D. 31. The backbones of DNA and RNA are formed by: A. B. C. D. E. 32. 3'-to-5' phosphodiester bond 2' to 3' phosphodiester bond Thymidine dimers ß-glycosidic linkage Nucleoside triphosphate bonds Certain locations (loci) in the human genome are termed hypervariable loci and are characterized by the presence of sequences that are repeated in tandem a variable number of times; i.e., they contain a variable number of tandem repeats (VNTRs). What is the chance that two siblings will be indistinguishable based on genetic testing for hypervariability at one particular VNTR locus? A. B. C. D. E. 33. Histone SLeacetylation correlates with gene inactivity Tamoxifen binding to the estrogen receptor prevents binding of the coactivator TFIID binds the TATA box element upstream of promoters and recruits TFIIA The proteolysis of the SREBP occurs in response to high levels of cholesterol 25% 33% 50% 75% 100% A mutation in the lac repressor protein eliminates its binding to the lac operator. The mutant strain displays: A. B. C. D. E. An inability to express the lactose operon-encoded genes under any circumstances An inability to express the lactose operon-encoded genes unless lactose is present and glucose is absent The same level of expression of the lactose operon-encoded genes under all circumstances The highest level of expression of the lactose operon-encoded genes only when glucose is absent whether or not lactose is present The highest level of expression of the lactose operon-encoded genes only when glucose is absent and lactose is present Medical School Biochemistry - Fall 2004 Block I Exam (Version 3- September 21, 2004) FOR EACH OF THE FOLLOWING MULTIPLE CHOICE QUESTIONS CHOOSE THE MOST APPROPRIATE ANSWER 9 34. A homeless man presents to the emergency room with sore and bleeding gums and states that he has recently lost several teeth. A dietary history indicates that he eats very little fruit or vegetables, mostly fast food. You diagnose a case of scurvy, which in large part is due to defective collagen synthesis. Which of the following steps in the biosynthesis of collagen is directly affected by this dietary insufficiency? A. B. C. D. E. 35. The secretion of tropocollagen into the extracellular matrix The formation of disulfide bonds that initiates tropocollagen formation The intracellular hydroxylation of proline and lysine residues The formation of collagen fibrils The extracellular oxidation of lysine residues Enzymes catalyze reactions and thus accelerate the rates of the reactions they catalyze by utilizing a number of different catalytic strategies. Which of the following catalytic strategies is/are utilized by the proteolytic enzyme chymotrypsin? 1. 2. 3. 4. A. B. C. D. E. 36. Formation of a covalent enzyme-substrate intermediate Strain and distortion of the substrate General acid-base catalysis Stabilization of charge using a metal ion 1, 2 and 3 only 1 and 3 only 2 and 4 only 4 only All four Sickle cell anemia is associated with a restriction fragment polymorphism because A. B. C. D. E. A single nucleotide change results in loss of an Mst II sight in the beta globin gene The amino acid substitution results in a change in electrophoretic mobility of the protein The mutation is associated with a three base pair deletion The mutation is associated with a change in the number of triplet repeats associated with the beta globin gene There is an expansion in the number of triplet repeats associated with the beta globin gene Medical School Biochemistry - Fall 2004 Block I Exam (Version 3- September 21, 2004) FOR EACH OF THE FOLLOWING MULTIPLE CHOICE QUESTIONS CHOOSE THE MOST APPROPRIATE ANSWER 10 37. The term secondary structure of proteins refers to: 1. 2. 3. 4. A. B. C. D. E. 38. If only 1, 2, and 3 are correct If only 1 and 3 are correct If only 2 and 4 are correct If only 4 is correct If all are correct Amplification of DNA by means of polymerase chain reaction requires: A. B. C. D. E. 39. Alpha helix Overall conformation Beta pleated sheet Subunit interactions Reverse transcriptase, heat-stable DNA polymerase' and two primers DNA ligase, heat-stable DNA polymerase and two primers Repeated cycles of annealing, extension, denaturation and re-annealing At lease two molecules of DNA as a starting template Restriction enzymes The heart (H) and skeletal muscle (M) isoforms of an enzyme differ in primary sequence at two positions. The H-form has glutamate and lysine whereas the M-form has glutamine and arginine. If heart damage can be assessed by measuring the ratios of the H and M isoforms released in blood, which of the following would most likely be used to determine if a patient had suffered a myocardial infarction (heart attack)? A. B. C. D. E. Affinity chromatography using a bound competitive inhibitor Enzyme activity analysis Isoelectric focusing Size-exclusion chromatography SDS-polyacrylamide gel electrophoresis Medical School Biochemistry - Fall 2004 Block I Exam (Version 3- September 21, 2004) FOR EACH OF THE FOLLOWING MULTIPLE CHOICE QUESTIONS CHOOSE THE MOST APPROPRIATE ANSWER 11 40. Which of the following analytical separation techniques can yield an estimate of the molecular mass of a protein? 1. 2. 3. 4. A. B. C. D. E. 41. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry Isoelectric focusing SDS-polyacrylamide gel electrophoresis Affinity chromatography 1, 2, and 3 only 1 and 3 only 2 and 4 only 4 only all four Many membrane-bound and secretory proteins are synthesized on the rough endoplasmic reticulum (RER). Following are events in the synthesis, of a secretory protein: 1. 2. 3. 4. 5. Docking of the ribosome-mRNA complex to the RER Translation of the signal sequence in the cytosol Removal of the signal sequence by a signal peptidase Binding of the signal recognition particle to the signal sequence. Release of completed protein into the lumen of the RER. Which of the following arranges the events in the correct sequence? A. B. C. D. E. 42. 1→2→3→4→5 2→4→1→3→5 2→1→4→5→3 1→3→4→3→5 2 → 4 → 1 → 5→ 3 Cysteine side chains are capable of forming: 1. 2. 3. 4. A. B. C. D. E. Salt bridges Disulfide bonds Double bonds Coordinate bonds with metals 1, 2 and 3 only l and 3 only 2 and 4 only 4 only All four 12 Answers 1. B 2. D 3. A 4. D 5. C 6. A 7. B 8. C 9. B 10. E 11. D 12. E 13. E 14. D 15. D 16. C 17. D 18. B 19. A 20. C 21. E 22. D 23. E 24. D 25. A 26. A 27. B 28. D 29. A 30. D 31. A 32. A 33. D 34. C 35. B 36. A 37. B 38. C 39. C 40. B 41. B 42. C 43. C 13