Examination III PHRM 836 Biochemistry for Pharmaceutical Sciences II December 19, 2014

Transcription

1 Examination III PHRM 836 Biochemistry for Pharmaceutical Sciences II December 19, 2014 Name: Instructions PHRM 836 Exam III Check your exam to make certain that it has 8 pages including this cover page. Ask for a new copy of the exam if you are missing any pages. 2. Use a pencil for filling in the answer sheet for computerized grading. 3. Write your name on the line above (this page) AND on the answer sheet for computerized grading. Also place your student ID number on the answer sheet. Fill in the circles underneath where you write your name and student ID number. Do NOT place any other identification (name or ID number) anywhere else on this exam or on the answer sheet. Also, do NOT fill in anything for section number. 4. Your answers to problems 1 through 23 will be graded by computer. All computer-graded questions will be worth three points each. Put your answers for these problems on the answer sheet and fill in the appropriate circle using a pencil. It is your responsibility to be certain that the answers for these problems are correctly marked on the answer sheet at the time you hand in your completed exam. You are strongly encouraged to double check this at the time you submit the answer sheet, as no points will be given for having mistakenly marked your answer sheet. The computer grading answer sheets will not be returned to the students, so you are encouraged to record your answers to the computer-graded questions on this exam as well as on the answer sheet. However, the computerized grading of your answers to these questions will be done solely on the basis of the optically scanned answer sheet, not on what is recorded on your exam. The course policy is that there will be no re-grading of the computer answer sheets. 5. Examination problems 24 through 28 are to be answered with short answers, brief essays, or drawings. Put your answer to each of these directly on this exam, in the space provided below each of these questions. 6. After completing your exam, both the exam and the answer sheet must be submitted for grading and both must be identified only with your name. 7. This is a closed-book, closed-notes exam. Calculators and electronic devices of any kind are not allowed to be used during this exam. Any electronic device that is not in a backpack, bookbag, purse, pocket, etc, will be considered to be in use, so put away all electronic devices including cell phones and calculators. Anyone observed to be using a calculator, any book, handouts, notes, printed or handwritten material of any kind, or the exam or answer sheet of any other student will be considered to have committed an act of academic dishonesty. Students that do so will not be allowed to complete the exam and will be given a zero for this exam. Also remember that the first instance of academic dishonesty also results in a grade of "F" in this course and reporting this episode to the Pharmacy Dean and the Dean of Students office.

2 PHRM 836 Exam III - 2 MULTIPLE CHOICE. For problems 1 to 23, select from the list immediately following each question the single most correct choice to complete the statement, solve the problem, or answer the question. Mark that answer on your answer sheet. [3 points each] 1. Other than reducing the production of ATP, what is the other effect that mitochondrial uncouplers have? Uncouplers reduce the synthesis of purines. Uncouplers reduce the synthesis of phospholipids and sphingolipids. Uncouplers increase the synthesis of fatty acids in the peroxisomes. Uncouplers increase the amount of peroxisomes in cells. Uncouplers increase the generation of heat by the mitochondria. Uncouplers increase the replication of mitochondria, thereby increasing their number in cells. Uncouplers alter the protein targeting system in cells, causing mitochondrial proteins to go to the cell membrane instead. Uncouplers block the acyl-carnitine transport of fatty acids into the mitochondria. 2. One way in which the metabolism of fructose is dissimilar from the metabolism of glucose is that fructose is metabolized by converting it to glucose, while glucose is metabolized by converting it to fructose. glucose metabolism begins with phosphorylation while fructose metabolism does not begin with phosphorylation. fructose is phosphorylated on carbon 1, while carbon 1 is never phosphorylated in glucose metabolism. fructose is metabolized primarily by the liver, while glucose is metabolized by all cell types. fructose metabolism is very rapid compared to glucose metabolism. fructose metabolism does not involve getting split into two trioses, unlike in glucose metabolism. 3. Human cells can biosynthesize - starting from acetyl-coa - free fatty acids that contain carbon-carbon double bonds that are located at least 12 carbons from the carboxylate end 9 carbons from the carboxylate end 6 carbons from the carboxylate end 3 carbons from the carboxylate end 12 carbons from the omega end 9 carbons from the omega end 6 carbons from the omega end 3 carbons from the omega end 4. In a normal-weight person, the primary lipid in the blood that is available for metabolism by most body tissues is free fatty acids bound to albumin fatty acids from triglycerides in lipoproteins free fatty acids bound to albumin during the fasting state and fatty acids from triglycerides in lipoproteins in the well-fed state. free fatty acids bound to albumin during the well-fed state and fatty acids from triglycerides in lipoproteins in the fasting state.

3 5. Beta oxidation of fatty acids in peroxisomes PHRM 836 Exam III - 3 never occurs only occurs in red blood cells cannot shorten chain lengths to less than 8 carbons cannot occur with very long chain fatty acids ( 20 carbons) preferentially occurs with longer chain fatty acids ( 20 carbons) preferentially occurs with shorter chain fatty acids ( 10 carbons) preferentially occurs with longer chain fatty acids ( 20 carbons) and cannot shorten chain lengths to less than 8 carbons 6. Why are foods that contain partially hydrogenated fat considered very unhealthy to eat? They contain more calories than food with other kinds of fat. They have the same calories as other fats but cause obesity at a much greater rate than other fats. They contain a fatty acid not found in other fats that very strongly activates PPARα. They contain a fatty acid not found in other fats that is worse for health than fully saturated fats. They contain less polyunsaturated fatty acids than other kinds of fat. They contain more fatty acids that lead to eicosanoids that increase risk of thrombosis. They contain fatty acids that bypass the normal regulation of fatty acid oxidation. 7. How many HMG-CoA molecules does it take to produce one molecule of cholesterol? Bile acids (also known as bile salts) are biosynthesized and/or metabolized in the cells of the small and large intestines lumen of the large intestine gall bladder liver adipocytes kidneys liver and lumen of the large intestine liver, gall bladder, and lumen of the large intestine macrophages

4 PHRM 836 Exam III Other than its role as a metabolic precursor, cholesterol s most important function in humans is to provide structure to the lipid droplets in cells to provide structure to lipoproteins to regulate cell surface receptor function to provide structure to the cellular plasma membrane to provide structure to serum albumin to provide structure to the nuclear membrane to make the inner mitochondrial membrane impermeable to most molecules 10. Sphingolipids are membrane lipids that cannot be made in sufficient quantities by mammals. lipids that are important in the storage and vascular circulation of triglycerides. only found in cells of neurological tissues. membrane lipids that contain a cholesterol. membrane lipids that contain one or more eicosanoids. membrane lipids that bind strongly to cholesterol. membrane lipids that contain a sphingosine. membrane lipids that always contain at least one sialic acid. membrane lipids that are highly polar because they contain a phosphate. 11. Why does aspirin have analgesic activity? Aspirin inhibits the enzyme responsible for the first step of production of prostaglandins. Aspirin inhibits the enzyme responsible for the first step of production of prostacyclins. Aspirin inhibits the enzyme responsible for the first step of production of thromboxanes. Aspirin inhibits the enzyme responsible for the first step of production of leukotrienes. Aspirin inhibits the enzyme responsible for the first step of production of HETEs. Aspirin inhibits the enzyme responsible for the first step of production of lipoxins. Aspirin inhibits the enzyme responsible for the liberation of arachidonic acid from phospholipids. 12. Why is acetaminophen more commonly used in hospitals than any NSAID, such as ibuprofen or indomethacin? Acetaminophen has a higher margin a safety for producing liver toxicity. Acetaminophen does not cause injury to the stomach lining Acetaminophen does not block thromboxane synthesis. Acetaminophen does not block synthesis of leukotrienes. Acetaminophen does not block synthesis of prostacyclins. Acetaminophen has a strong activity for reducing fever. Acetaminophen lacks the adverse neuropathology that can result from NSAID treatment. Acetaminophen has very strong anti-inflammatory activity.

5 PHRM 836 Exam III If arginine is made during the urea cycle, why is it that childrens health and development are dependent on dietary arginine? Arginine made in the urea cycle is made only as an enzyme-bound intermediate. Arginine made in the urea cycle is hydrolyzed as soon as it is made and is not available for protein synthesis. Arginine for protein synthesis is made by the kidneys using citrulline from the intestines. The urea cycle only functions when excess amino acids are present, and this never happens in children. Arginine produced by the urea cycle cannot leave the liver and is only useful for protein synthesis in the liver. None of the above 14. When a L-α-amino acid reacts with transaminase, the initial enzyme-bound intermediate is an α-keto acid pyridoxal phosphate amino acyl coenzyme A amino acyl - AMP a ketimine an aldimine 15. The first and last intermediates in the biosynthesis of heme are biliverdin and bilirubin uroporphobilinogen III and coproporphobilinogen III protoporphyrin IX and protoporphyrinogen delta-aminolevulinate and porphobilinogen delta-aminolevulinate and hydroxymethylbilane delta-aminolevulinate and protoporphyrin IX 16. Of the functions of heme-containing proteins in humans, what one is quantitatively the most common? Delivering oxygen to a substrate in an enzyme-catalyzed reaction Transporting dioxygen Participating in mixed function oxidase reactions such as in cytochrome P450 Carry electrons in mitochondrial electron transport Serve as a sensor for the concentration of iron in cells 17. The protein which transports iron in the blood plasma is ferritin hemoglobin myoglobin transferrin albumin ceruloplasmin ferroportin hephaestin hepcidin aconitase

6 PHRM 836 Exam III The fairly common hereditary disorder that results in storage of too much iron in the body is jaundice ADA-SCID porphyria cholestasis anemia hemochromatosis Lesch-Nyhan syndrome favism kernicterus alkaptonuria 19. Allopurinol, the primary therapeutic agent used for gout, increases excretion of urate in the kidneys increases oxidation of urate leading to formation of alantoin decreases production of urate from xanthine decreases de novo synthesis of purine nucleotides increases salvage of purines inhibits ribonucleotide reductase decreases synthesis of phosphoribosyl pyrophosphate helps break up sodium urate crystals in the joints 20. Hereditary deficiency of adenosine deaminase results in accumulation of a metabolite that allosterically inhibits another enzyme, and that secondary inhibition ultimately causes the significant pathology of this hereditary disease. What enzyme plays this critical role in this hereditary disease? ribonucleotide reductase thymidylate synthase PRPP synthetase xanthine oxidase urate oxidase hypoxanthine-guanine phosphoribosyl transferase glutamine phosphoribosylpyrophosphate amidotransferase carbamoylphosphate synthetase II 21. Lesch-Nyhan syndrome is caused by hereditary inactivity of what enzyme? ribonucleotide reductase thymidylate synthase PRPP synthetase xanthine oxidase urate oxidase hypoxanthine-guanine phosphoribosyl transferase glutamine phosphoribosylpyrophosphate amidotransferase carbamoylphosphate synthetase II

7 PHRM 836 Exam III In diabetic patient care, exercise, particularly strength and muscle building types of exercise, is often recommended. Why is exercise helpful for diabetic patients? It improves memory, so patients remember to take their insulin and eat right. It improves mental focus so patients will more accurately estimate their insulin needs. It increases muscle, which helps burn calories and increase basal metabolic rate. It increases muscle which is the largest tissue contribution to insulin-induced glucose utilization. It increases generation of lactate by muscle which can go to the liver and be converted to glycogen. It increases heart tone and lung capacity which benefits one s stamina for everyday tasks. It increases heat generation, thereby sparing fatty acid oxidation used for thermogenesis. 23. Glucophage (metformin) is active against type 2 diabetes mellitus because its activity causes increased secretion of insulin decreased reuptake of glucose in the kidneys decreased carbohydrate digestion and absorption of glucose from the lumen of the intestines decreased signaling by PKA in response to glucagon suppression of gluconeogenesis in the liver increased glycogen synthesis in muscle ESSAY PROBLEMS. Write your answers to problems 24 to 28 in the space immediately below each problem. 24. [6 points] Thiazolidinediones, also known as glitazones, are orally active for treatment of type 2 diabetes mellitus. Answer the following three questions about glitazones. a. [2 points] What protein binds glitazones and does this binding of glitazone to the protein activate or inhibit the protein s function? b. [2 points] What is the main molecular result in cells that is directly caused by the change in the activity of the protein that binds glitazones? c. [2 points] What impact does the change caused by glitazones have on metabolism of energy molecules that explains its anti-diabetes activity? 25. [6 points] Vitamin B 12 (cobalamin) is known to be involved in only two distinct enzyme-catalyzed reactions. One of those two reactions is unique to the general area of amino acid metabolism. What is that enzyme-catalyzed reaction that is unique to amino acid metabolism and which involves cobalamin?

8 26. [6 points] Answer the following three questions about ketosis. a. [2 points] What is ketosis? PHRM 836 Exam III - 8 b. [3 points] Describe two distinct situations where ketosis occurs. c. [1 point] Does having ketosis have a serious impact on one s health? (yes or no) 27. [6 points] Answer the following questions about the catabolism of heme. a. [2 points] What is the name of the large carbon-containing product of the first enzyme-catalyzed reaction of heme catabolism? b. [1 point] What is the name of the skin indication that involves elevated levels of heme catabolites? c. [3 points] The reasons for the occurrence of elevated levels of heme catabolites are grouped into three general types. What are those three general types of reasons? 28. [7 points] A1c can be used to diagnose diabetes mellitus. Answer the following questions about A1c. a. [2 points] What is A1c? b. [2 points] In general terms, how is A1c formed? c. [1 points] What causes A1c to be formed at a greater rate? d. [2 points] Why is it justified to use elevated A1c as an indication that is diagnostic for diabetes?