Final Exam, Chemistry 153C, Fall, 2004 Please print and sign your full name below and provide your student ID. On the subsequent pages, please print your last name. The exam should be completed in 3 hours. The only materials allowed on your desk are pencil/pen and eraser. Calculators are not needed and books and notes are not allowed. Printed Name _____ Last, First Student ID # Signature __ Points: Page 2 /25 Page 3 /15 Page 4 /18 Page 5 /20 Page 6 /21 Page 7 /16 Page 8 /16 Page 9 /18 Page 10 /19 Page 11 /21 Page 12 /11 Total /200Page 2 of 12 Final Exam, Chem 153C, Winter 04 Name______________________________ 1. a. In the mammalian pathway for the synthesis of arginine, glutamate serves as a precursor. Specifically the nitrogen atoms and 5 of the 6 carbon atoms can all be derived from glutamate. Show a pathway starting from glutamate in which you show how glutamate provides the nitrogen atoms and the carbon atoms (except one) to form arginine. Also in the final structure of arginine, mark the carbon atom that did not originate from glutamate and indicate the source. Include the structures, name the cofactors, and include compartmentation. Mechanisms are not necessary. (25 points)Page 3 of 12 Final Exam, Chem 153C, Winter 04 Name______________________________ 1.b. Fumarate is a byproduct that can be recycled. Show the recycling pathway of fumarate back to aspartate with structures and provide the names of cofactors. Enzyme names are not necessary. (8 points) 2. Malaria is caused by the parasite Plasmodium falciparum. As a natural adaptation, African populations have a common mutation in the gene coding for the enzyme (1 point): _____________________________________ Explain briefly the pathway that is affected and the biochemical reason for this mutation? (4 points) The malaria parasite has developed an adaptation to help overcome the mutation in humans. What is it? (2 points)Page 4 of 12 Final Exam, Chem 153C, Winter 04 Name______________________________ 3. Glycinebetaine enhances tolerance to salt and cold stress in plants and is synthesized from serine via choline. Starting from a central metabolic intermediate, derive a pathway in which serine, followed by choline, and then glycinebetaine can be synthesized. (18 points) serinecholineCH3CH3+CH3-N-CH2-COO-glycinebetainePage 5 of 12 Final Exam, Chem 153C, Winter 04 Name______________________________ 4. Starting with central metabolic pathway intermediates, propose a biosynthetic pathway for the synthesis of these hypothetical amino acids. Use structures for reactants and products; however, it is NOT necessary to draw out mechanisms. Cofactors should be indicated by either name or structure. Fully justify any unusual chemistry you propose and wherever possible use a biochemical precedent for each of the reaction steps in the pathway. (10 points for each) (a) +NH3-CH-CH2-CH2-NH3+ COO- +NH3-CH-CH2-NH3+ COO- (b)Page 6 of 12 Final Exam, Chem 153C, Winter 04 Name______________________________ 5. In MCAD (medium chain acyl dehydrogenase) deficiency, what is the metabolic defect and what products are not metabolized. ( 3 points) Patients with MCAD deficiency that have been fasting have hypoglycemia. Indicate the key enzyme that needs to be activated to prevent hypoglycemia and show the reaction it catalyzes. Structures are not necessary, but cofactors should be indicated. (6 points) 6. The following compounds are great smelling substances that plants make. These molecules are synthesized from intermediates that we have seen in the biosynthesis of cholesterol. For each structure, name the latest intermediate (in common with the cholesterol biosynthetic pathway) that gives rise to the oil (I do not want you to put acetyl CoA or mevalonate—put the last intermediate that would be in common in the cholesterol biosynthetic pathway). Then draw out their structures so that their orientation matches as closely as possible that of the product shown. Beta-santalol (sandalwood oil) (3 points) Beta-pinene (pine oil) (3 points) b. For Beta-santalol, calculate the number of energy molecules required to make the compound from citrate. _______ATP Show your work (6 points) _______NADPH ________NADHPage 7 of 12 Final Exam, Chem 153C, Winter 04 Name______________________________ 7. Glutamate synthetase, which has been shown to occur in microbial species and higher plants, catalyzes the following reaction: NADPH + H+ + L-glutamine + α-ketoglutarate → 2 L-glutamate + NADP+ As the name implies, this enzyme is thought to be responsible for the biosynthesis of glutamate in these organisms. (a) Give an indication of the manner in which the three substrates must be participating in the overall transformation catalyzed by glutamate synthetase. Include structures (12 points) (b) Why might this reaction be considered a part of an energetically more favorable sequence for the synthesis of L-glutamate than the L-glutamate dehydrogenase reaction? ( 4 points)Page 8 of 12 Final Exam, Chem 153C, Winter 04 Name______________________________ 8. You are doing a set of metabolic experiments on mice to study glycogen breakdown and synthesis. Consider the following situations and answer the questions or based on your knowledge from 153C, comment on the state (more or less phosphorylated, bound or not bound) and activity (more or less active) of the following components. a. The mouse has been engineered so that muscle cells contain a caged Ca2+ product. Upon electrical stimulation, the product releases Calcium into the muscle cell directly. You give an electrical stimulation and notice that the animal leg muscles start twitching. i. The important component in glycogen breakdown/synthesis cascade is _________________________(1 pt). ii. Phosphorylase kinase activity (1.5 pt) iii. Glycogen phosphorylase activity (1.5 pt) iv. Glycogen synthase activity (1.5 pt) b. A mouse model has a mutation in which the stimulatory subunit of the heterotrimeric G-protein is always bound to GTP. i. Amount of cAMP (1.5 pt) ii. State and activity of Protein Kinase A (1.5 pt) iii. State and activity of Inhibitor protein