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1 Fa14%BIBC102%final,%page% 1%! Hello Non-Minion Metabolites! This test will be collected for grading. The graded exams will be available for pickup sometime next week. Stay tuned. The key will be posted on the website TONIGHT. Feel free to register comments, complaints, questions, or corrections to me by . We will consider those suggestions or observations during the grading. Like many things, it takes a village to create an optimal final. A village full of test takers I have enjoyed teaching this class. I always learn a lot, and appreciate the energy and dedication you all show. To commemorate the event, and to replenish your glycogen stores, will have a bunch of pizza outside the test room, which we can eat. Happy Holidays! Summation Page 2 (out of 16) Page 3 (out of 12) Page 4 (out of 12) Page 5 (out of 16) Page 6 (out of 16) Page 7 (out of 13) Page 8 (out of 13) Page 9 (out of 15) Page 10 (out of 11) Page 11 (out of 11) Page 12 (out of 15) Total (out of 150)

2 Fa14%BIBC102%final,%page% 2% 1) The Ami-ning of life. There are two amino acids drawn, one is alanine, and the other is glutamate. Answer the following questions about these two often-encountered amino acids a) 1 pt In the provided lines, write the one letter code for each: b) 4 each Both alanine and glutamate have cognate α-keto acids that are common metabolites. Draw the structure of each cognate α-keto acid and include the name of each on the line below each structure. You have seen both of these molecules many times in this class. S, H and D are the three amino acids that comprise the chymostrypsin catalytic triad. c) 1.5 pts What are the full names of these three amino acids: S: D: H: d) 1 pt Briefly (one sentence or less) describe what reaction chymostrypsin catalyzes: e) 3 pts Briefly describe what each amino acid does as part of the catalytic triad (one line each) : S: D: H: g) 1.5 pts For the amino acid pictured, write its name and one letter code and circle the carbon that ends up in urea during the urea cycle

3 Fa14%BIBC102%final,%page% 3% 2) All s well that enz well A laboratory is studying an enzyme inhibitor called M. M inhibits its target enzyme by lowering the Vmax without affecting the Km. Answer the following questions based on this statement a) 1 pt Does M alter the concentration of substrate that is needed to attain 50% saturation of its target enzyme? Yes or no, and why (one sentence) b) 1 pt Does M alter the observed kcat of its target enzyme? Yes or no, and why (one sentence) c) 3.5pts In the box provided, sketch a simple substrate vs Vo plot, showing the behavior of the enzyme in the presence and absence of M. Include and label both axes, show which curve is measured in the presence and absence of M, include the position of the Km and Vmax for each curve, on your plot. d) 3.5pts Now do the same for the enzyme in the presence and absence of M using a Lineweaver-Burke plot. Again, label the axes, show Km, Vmax for enzyme in the presence and absence of M Plot%for%c% Plot%for%d% e) 1 pt A Michaelis-Menton enzyme has a Km of 10 µm. What is the fraction (or percent if you like) of maximal activity that will be observed with a substrate concentration of 40 µm? Write answer in the provided box to the right: f) 2 pt An enzyme shows highly cooperative behavior. What can you say about the shape of that enzyme s S vs Vo curve, and the probable structure of the enzyme molecule?

4 Fa14%BIBC102%final,%page% 4% 3) Deja Glu I used this gallery of pictures last year. Changed the questions.. A B C D E F G H I J K L a) 3pts First, match up the best letter above with the standard abbreviations below. Use the caps. Use the spaces. Use all the letters. Glu PEP Lac DHAP 2PG Fr6P G6P G3P 1,3bPG Pyr Fr1,6bP 3PG b) 6.5 pts Now using the standard abbreviations (like Pyr) of each structure, write out the glycolytic pathway. Include things like NAD+ and ATP, etc as you need them. I will get you started Glu 4) 2.5 pts New Glu Too! Use the standard abbreviations of the molecules above (like Pyr, etc) to answer the following questions about gluconeogenesis a) Which molecule is directly produced from oxaloacetate during gluconeogenesis b) Which is a substrate of glyceraldehyde-3-phosphate dehydrogenase during gluconeogenesis c) Which molecule is directly converted into a powerful regulator of gluconeogenesis d) What is the end product of gluconeogenesis in liver e) What molecule is taken up by the liver during the Cori cycle to produce glucose

5 Fa14%BIBC102%final,%page% 5% 5) The Tour De Krebs- as far as cycles go, Krebs is the king. Below is a list of parts. AcCoA Fum Cit Suc-CoA Iso OAA αkg Mal Suc a) 12.5 pts Using them (no structures needed) draw a reasonable depiction of the Krebs cycle. Include other reactants and products that are consumed or produced. (And you don t need to bother with that annoying water that exits and re-enters in the aconitase reaction. ). Keep your cycle above the line below to preserve TA sanity. b) 1 pt The picture shows citrate. Draw the structure of isocitrate in the provided box next to citrate. c) 0.5 pt In your structure of isocitrate, circle the two carbons that most recently came from AcCoA d) 2 pts In The Transformation, we read about a new cancer drug that inhibits a mutant version of isocitrate dehydrogenase (IDH). We discussed this in class as well. The mutant IDH converts α ketoglutarate (αkg) into a cancer-specific molecule called 2OH-glutarate (2OHG). Write that reaction including structures of the akg and 2OHG. Remember, it is a reduction. Only Minor Stress Guaranteed if you recall the Name Game

6 Fa14%BIBC102%final,%page% 6% 6) Glyoxalicious! In class we discussed a variant of the Krebs cycle called the glyoxylate cycle. It that plays a key role in anabolism in plants, microorgansims, etc. a) 1 pts Why can the glyoxylate cycle allow carbon derived from AcCoA to be used to produce glucose, while the Krebs cycle can not? b) 1 pts Write the net reaction of the glyoxylate cycle, to show what is consumed and what is produced. No structures needed. c) 3.5 pts There are two enzymes unique to the glyoxylate cycle. Choose ONE of these two enzymes, isocitrate lyase OR malate synthase, and write the reaction that enzyme catalyzes, including the structure of glycoxylate, and the structures of the substrates and products. No, you don t have to write the structures of things like ATP, or CoA, but include them if needed. Indicate which of the enzymes you have chosen. 7) The 2016 Presidential Electrons The picture shows a the electron transport chain, using the roman numerals rather than the elaborate enzyme names. a) 6.5 pts For each arrow, include what is being consumed, produced, moved, or whatever to complete the picture of the ETC as we know it. For example, you might add NADH somewhere Also, add the name of the unlabeled blob between complexes III and IV. b) 2 pt The ETC produces energy to drive ATP synthesis. How is energy stored during the ETC, and how is it used to drive ATP synthesis (One sentence) c) 1 pt The UCP proteins and weak organic uncouple the ETC from ATP synthesis. How do they do this? (one sentence) d) 1 pt Add an arrow to the picture to represent the action of a UCP

7 Fa14%BIBC102%final,%page% 7% 8) Liver the Giver: The liver is in a very real sense the Minister of Glucose. We have even called the liver a glucostat for the body, since it is so important in keeping blood glucose in a safe range. a) 2 pts When we have had a meal, and insulin is abundant while glucagon is low, what happens to the following LIVER processes (a word, phrase, or clause is fine) glycolysis: glycogen synthesis: gluconeogenesis: glycogenolysis: b) 2 pts When we have fasted for awhile, and insulin is low and glucagon is high, what happens to the following LIVER processes (a word, phrase, or clause is fine) glycolysis: glycogen synthesis: gluconeogenesis: glycogenolysis: c) 2 pts The picture shows a key regulatory molecule we learned about in class, called fructose 2,6 bisphosphate. Fr2,6bP is an important part of glucose regulation in the liver. What are its direct effects (phrase fine; none is fine if true) on the following processes glycolysis: glycogen synthesis: gluconeogenesis: glycogenolysis: d) 4 pts What are the two enzymes that Fr2,6 bp affects and how does it affect them (phrase fine). Use the full name if you can, abbreviation is OK if that is all you have. 1) : 2) : e) 2 pts Both glucagon and insulin alter cellular levels of Fr2,6bP in the liver. What is the effect of each on this key regulator of glucose? Glucagon: Insulin: f) 1 pt Why is glucose produced from glycogen in liver released into the bloodstream, while that produced in muscle is not. I am looking for an enzyme that explains this difference (one sentence)

8 Fa14%BIBC102%final,%page% 8% 9) It s like we just Met(formin) In a paper just published this year, a new explanation for the action of the diabetes drug metformin was proposed. But first, lets talk about this widely used drug. a) 0.5 pts Metformin is given to diabetics because it slows gluconeogenesis. Why would this be a useful effect for diabetics (one sentence)? Gluconeogenesis can occur using pyruvate as a starting product. Since the glycolytic enzyme pyruvate kinase can not be used, bypass reactions occur instead b) 2 pt First, write the pyruvate kinase reaction (no structures needed) as it occurs in glycolysis, including substrates and products appropriately abbreviated.: c) 5 pts Now, using similar abbreviations, write the pair of reactions that allow the conversion of pyruvate into a glycolytic intermediate. The enzymes used are pyruvate carboxylase and PEP carboxykinase. Include all reactants and products. 10) Reformin a hypothesis: The surprising finding is that metformin is a potent inhibitor of glycerol-3-phosphate dehydrogenase (G3PD; Madiraju et al., Nature 510, 542 (2014)). That s right, metformin decreases the activity of G3PD, which is NOT the glycolytic enzyme GAPDH, but rather an enzyme we encountered in the glycerophosphate shuttle. Hmmm. a) 1 pt What is the glycerophosphate shuttle? One sentence b) 2 pts Recall that the glycerol phosphate shuttle involves DHAP and glycerol-3-phoshpate. Using the structures, write the reaction of G3PD, that occurs on the mitochondrial membrane. You can use either FAD or Q as an acceptor (there is a hint) c) 1 pt What shuttle functions like the glycerolphoshpate shuttle? d) 1 pt Normally, these two shuttles are thought (and taught) to allow glycolysis to continue. What do each of these shuttle do that allows glycolysis to continue? (Hint: it is similar to why fermentation reactions occur) One sentence So why does inhibiting G3PD inhibit glyconeogenesis?! That is still an open question. e) 1 pt One model is that a substrate used in gluconeogenesis is no longer produced when G3PD is inhibited. Is a metabolite that can be used to make glucose produced in the G3PD reaction? If so, what is it? f) 0.5 pt Does making glucose from the metabolite in e) require any ATP? Why?

9 Fa14%BIBC102%final,%page% 9% 11) 20 marathons gone to waste. Our lipid stores are an incredibly important source of energy. The main process for extracting energy from lipids is β-oxidation of fatty acids. a) 1 pts What are the main products of β-oxidation: β-oxidation involves a set of cyclical reactions, making it easier to learn because they samefour are used multiple times. The picture shows the first reaction, stating with an acyl- CoA molecule. b) 4.5 pts Continue the process until one cycle is complete. No need for enzyme names. Include all substrates and products. Use the same level of detail as the starting picture c) 1 pt Carnitine is a product sold at many fine establishments. What is the function of carnitine in β-oxidation of fatty acids? One sentence 12) Holiday time is lipogenesis time! Let s now talk about synthesis of fatty acids. a) 2.5 pts Acetyl CoA carboxylase (ACC) is the rate-limiting enzyme of fatty acid synthesis. Write the reaction catalyzed by ACC. Draw the final product made from CH 3 -CO-SCoA and write the name of this product. Include names of other substrates and products. b) 4 pts Like in β-oxidation, a set of cyclical reactions are used grow a fatty acid chain. The growing chain is connected to ACP in the fatty acid synthase (FAS) complex. Complete one cycle of synthesis from the picture shown (3 total reactions). Include substrates and products needed in each reaction. No enzyme names needed. c) 1 pts Here is a lovely fact: malonyl-coa is a potent allosteric inhibitor of carnitine palmitoyl transferase. Why does that make physiological sense? (one sentence) d) 1 pt How is citrate involved in the synthesis of fatty acids (one sentence)?

10 Fa14%BIBC102%final,%page% 10 13) Fructose is the new F Word There is increasing belief that consumption of fructose may be a uniquely bad consequence of the industrial food revolution. As we have discussed, fructose has a unique fate. It is primarily metabolized by the liver, and enters glycolysis by a different route. The description of this unique liver route is included below. From what you know, write the reactions including the structures of the fructose derived metabolites like we always do. Include other substrates and products as needed. (Hint phosphorylation reactions need ATP) a) 3 pts Fructose is phosphorylated to Fr-1P by fructokinase. b) 3 pts The Fr1P is then cleaved by aldolase B into glyceraldehyde and DHAP c) 1.5 pt Glyceraldehye is phosphorylated by glyceraldehyde kinase to produce our old friend G3P The two final 3 carbon products of this set of reactions are the same as those produced by glycolysis. So how bad could this be? Lets compare their generation to glycolysis d) 1 pt What are the two final 3 carbon molecules produced that are also found in glycolysis? (abbreviations fine) e) 1 pt How many ATP were used to get to the two 3 carbon glycolytic metabolites? Is this different from glycolysis? (number, and one sentence) f) 1.5 pt Unlike the case in glycolysis, this route of fructose metabolism is not regulated by insulin or glucagon. Why not? (One sentence) Interesting Note (no question) In 2013, Lanaspa et al. demonstrated that in mice missing both copies of the fructokinase gene, many of the bad effects of obesity-causing diets were drastically decreased. Lanaspa et al. Nat Commun. 4:2434 (2013). This is intriguing evidence that this rogue pathway for fructose may be very important. Stay tuned young metabolites

11 Fa14%BIBC102%final,%page% 11 14) Pur-ity of essence One of the most important metabolites we discussed are purines and pyrimidines. They are of critically important in RNA and DNA metabolism, but also serve many metabolic roles. a) 2 pts The picture shows a key molecule in purine and pyrimidine metabolism. What is it called (abbreviation fine) and why is it important? Name: Importance: b) 1 pt Circle the OH in the picture that is removed by the action of ribonucleotide reductase when DNA precursors are being made. c) 3 pts The 1 st enzyme of pyrimidine biosynthesis is called carbamoyl phosphate synthetase. This enzyme uses bicarbonate and ammonia and ATP to produce carbamoyl phosphate that is employed in the first step of pyrimidine synthesis. Draw carbamoyl phosphate in the box d) 1 pt What amino acid then reacts with carbamoyl phosphate to start pyrimidine synthesis going? (name is fine) e) 1 pt When purines are catabolized, what is the final end product that must be excreted called? f) 1 pt How is the molecule in e) important in the disease gout? (one sentence) g) 2 pt What is purine salvage, and how do we know it is important physiologically? No reactions needed

12 Fa14%BIBC102%final,%page% 12 15) Truth Detector 15 pts Answer T or F for each; best answer 1) ketone bodies are produced in the liver when glucose is low 2) ketone bodies are produced in many tissues 3) ketone bodies are used as a fuel by many tissues 4) HMG-CoA is produced during ketone body synthesis and during sterol synthesis 5) both the ketone body pathway and the sterol pathway occur in the same cell compartment 6) acetyl-co A is generated by catabolism of ketone bodies 7) Type II fibers are used for high power low endurance actions 8) A specific allosteric regulator is produced to control the urea cycle 9) Most of the glucose released from glycogen breakdown comes from hydrolysis of α1 4 glycosidic bonds 10) UDP-glucose provides the glucose monomers for glycogen production catalyzed by glycogen synthase 11) glucose is released by glycogen phophorylase as glucose-6p 12) phosphorylation decreases the activity of both glycogen synthase (GS) and of glycogen phosphorylase (GP) 13) glucagon causes phosphorylation of both GS and GP 14) Type I diabetics are typically obese 15) Biotin is frequently used as a cofactor in carboxylation reactions 16) The Warburg effect indicates that cancer cells can not perform mitochondrial metabolism 17) Cancer cells are dependent on fatty acid synthesis 18) ATP-Citrate Lyase (or citrate lyase) generates AcCoA used for lipid synthesis 19) Caloric restriction (CR) causes longer lifespan in many organisms 20) SIR2 is an NAD+ dependent deacetylase 21) A fraction of electrons during the ETC produce reactive oxygen species (ROS) that can damage mitochondria 22) Gluconeogenesis and glycolysis are usually activated simultaneously in the liver 23) The rate limiting step for urea synthesis is the reaction that includes urea as a product. 24) Acetyl coa carboxylase (ACC) produces glyoxylate as a product 25) Plants can produce glucose from AcCoA produced during FA oxidation 26) CDP can be used to carry diacylglycerol or headgroups in phospholipid synthesis 27) Glycogen branches start with an α1 6 glucose linkage 28) Muscle blood flow is massively upregulated during exercise 29) Creatine-P provides more power than glycolysis in muscle movement 30) Anabolism is a festive and non-denominational feature of the Holidays