1FROM: C.F. CLARKE CH-2ADept. of Chemistry and BiochemistryUniversity of California, Los Angeles607 Circle Drive SouthLos Angeles, CA 90095-1569CH-2ATO:2Chemistry & Biochemistry 153C Winter 1999 Name____________________________________Student I.D. #____________________________FINAL EXAMINATION 23 March 1999 Total Score and Grade on Final _____________(220 points, 9 pages, 180 minutes)Total Score in Class _____________PLEASE READ EACH QUESTION VERY CAREFULLY!Grade in Class _____________POTENTIALLY USEFUL CONSTANTS:F = 23 kcal.mol-1 .volt-1; R = 0.00198 (kcal.mol-1 .°K-1)1. (50 points) (a) (30 points) Shown below is a mixed triacylglycerol. Show how aliver cell would catabolize this lipid via beta oxidation to acetylCoA andpropionylCoA units. Write out the structure of each of the intermediates formedduring the beta-oxidation. Indicate use of cofactors by name. It is notnecessary to indicate mechanism.CH2-O-C CH-O-C CH2-O-COOO3(b) (20 points) What number of ATP equivalents is produced by the oxidation of thetriacylglycerol in part (a) to CO2? State your assumptions and logic for fullcredit.42. (40 points total)(a) (10 points) Membrane lipids are extremely sensitive to oxidative damage. Drawthe structure of 1-Linoleoyl-2-arachidonyl-phosphatidyl-serine. (Linoleic acid =C:18, cis ∆9,12) (Arachidonate acid = C:20, cis ∆5,8,11,14). Show the formation ofa lipid peroxy radical on this phospholipid molecule.(b) (10 points) Show one example of one round of lipid autoxidation. (Illustratethe attack on a neighboring side chain).5(c) (10 points) The cell contains various small molecule antioxidant defenses toquench such reactions. Draw out the complete structure of coenzyme QH2(the reducedor hydroquinone form) and show the mechanism involved in quenching the lipid peroxyradical formed in part (a).(d) (10 points) Cells contain a specific glutathione peroxidase enzyme that acts onorganic hydroperoxides. Write out the balanced reaction catalyzed by this type ofglutathione peroxidase when it comes in contact with the lipid peroxide drawn inpart (c). You may indicate cofactors by name. Why is this reaction beneficial tothe cell?3. (10 points) Studies in India have shown that children with riboflavin deficiencyare more resistant to malaria. Explain how a decreased level of riboflavin might beexpected to PROTECT against malaria.64. (26 points total) Glutamine is the amino group donor in the formation of manybiosynthetic processes. In E. coli, its synthesis via glutamine synthetase is underan elaborate control system.(a) (20 points) Write out the complete chemical mechanism for the reactioncatalyzed by glutamine synthetase. Include complete structures of cofactors andindicate electron movements with appropriate arrows.(b) (6 points) This enzyme is covalently modified depending on the conditionsfound in the cell. The modifying enzyme, adenyltransferase, is also subject tomodification itself. What is the state of Glutamine Synthetase (GS) andAdenyltransferase (ATase) under the following conditions?GS....ATase(1) High [glutamine](2) High [αKG](3) High [ATP]75. (34 points) Propose a synthetic scheme for vitamin E (alpha tocopherol) using anintermediate of the isoprene biosynthetic pathway, common coenzymes and homogentisicacid (shown below) as the aromatic ring precursor. Draw out the complete structureof any required cofactors, and show electron movements with appropriate arrows.OHOCH33HC3HCH3CH33HCOHOH-OOC-CH286. (20 points) Draw out the mechanism for the conversion of tryptophan to 5-OHtryptophan. Draw out the "business end" of any required cofactors, and showelectron movements with appropriate arrows.NCH2-CH -NH3+COO-5tryptophan97. (40 points) Eukaryotic cells are able to convert tyrosine into 4-hydroxy-benzoicacid, the aromatic ring precursor for the synthesis of coenzyme Q. Propose abiosynthetic pathway for the synthesis of 4-hydroxy-benzoic acid from tyrosine. Usestructures for reactants and products, however, it is NOT necessary to draw outmechanisms, and cofactors can be indicated by either name or structure. Whereverpossible, indicate a biochemical precedent for each of the reaction steps in thepathway. For each reaction that you draw, give an example of the most similarreaction that we discussed in class (you can simply name the enzyme or describe itssubstrates and products). Fully justify any unusual chemistry you propose!COOHOH4-hydroxy-benzoic acid108. (30 points) Site directed mutagenesis has been used to study the role ofspecific amino acid residues in the mechanism of the human aspartate aminotransferase enzyme. Substitution of a lysine in place of an active site arginineresults in an enzyme that is much less specific. The reactions catalyzed by thisaltered enzyme result in a 100-fold increase in side reactions -- resulting inracemized, as well as decarboxylated products. By writing out the mechanism of thereaction catalyzed by this enzyme, provide a chemical explanation that accounts forhow such "side reactions" might occur. Indicate the formation of the normalproduct, as well as the products produced by these side