Unit 14 1 UNIT 14 PART A: FATTY ACID DEGRADATION PART B: FATTY ACID SYNTHESIS The oxidation of long chain faty acids to acetyl CoA is a central energy yielding pathway in animals and some bacteria. The electrons removed during faty acid oxidation, and oxidation of acetyl CoA via the TCA cycle, pas through the mitochondrial respiratory chain and drive ATP synthesis. PART A: FATTY ACID EGRADATION Asignment: Nelson & Cox, pp. 346, 647 - 656. 1. Faty acids are stored in adipose cels as triacyl glycerol. Draw the structure of triacyl glycerol using R to represent the long chain faty acid tail (p. 346). 2. Define the following terms (p. 649): a. chylomicrons b. apolipoproteins 3. Use Fig. 17-3 (p. 650) to ilustrate the following points: a. Activation of lipase in adipocytes through hormone sensitive amplificaton. (Note: a cascade like the one that activates glycogen phosphorylase also activates hormone sensitive lipase) b. Using structures, write a balanced chemical equation for the reaction catalyzed by lipase (p. 649). Unit 14 2 c. How are the hydrophobic faty acids stabilized in the blood as they are transported to tisues (p. 649)? d. What is the fate of the glycerol backbone (Fig. 17-4, p. 650 - note dihydroxyacetone phosphate is common to glycolysis and gluconeogenesis)? e. Using structures, write a balanced chemical equation for the cytoplasmic reaction that results in activation of faty acids (Fig. 17-5, p. 651). What aspect of the activation proces drives the reaction to completion? f. Where in the eukaryotic cel does faty acid oxidation occur (p. 650)? g. Discuss how the activated faty acid is caried into this membrane bound compartment (pp. 650 - 652). 4. Discuss the thre stages through which energy is derived from faty acid degradation (Fig. 17-7, p. 653). 5. Fig. 17-8 (p. 653) shows the details of a single round of ?-Oxidation. Note that you wil be responsibile for the types of reactions involved and the structures of the intermediates - but not the names of the compounds or the specific enzymes involved. Which reactions of the TCA cycle are similar to reactions in ?-Oxidation? 6. Write the net reaction for the ?-Oxidation of palmitoyl CoA (equation 17-3, p. 654). a. Considering the P/O ratios for NADH and FADH 2 that you learned in Unit 12, how many ATPs can be generated through subsequent oxidation of reduced flavin (FADH 2 ) and pyridine (NADH) nucleotides? (equation 17-4, p. 655) b. The acetyl CoA now enters the TCA cycle. Review the yield of reduced cofactors and GTP from complete oxidation of acetyl CoA in the cycle. How many phosphoanhydride bonds can be made from the oxidation of acetyl CoA? (equation 17-5, p. 655) c. What is the total yield of ATP formed during the oxidation of one molecule of Palmitoyl CoA (Table 17-1, p. 656)? Unit 14 3 PART B: FATY ACID SYNTHESIS Lipids are the principle form of stored energy in most organisms, as wel as major constituents of cel membranes. The ability to synthesize a variety of lipids is esential to al organisms. Like many biosynthetic pathways, the reactions in the biosynthesis of lipids require energy and reduction. ATP is utilized as a source of energy, and reductive power is furnished by NADPH. The ATP is derived directly from glycolysis, the TCA cycle, and indirectly via oxidative phosphorylation of reduced coenzymes. The NADPH is produced, in part, in the proces of faty acid synthesis. Additional required NADPH is produced in the pentose phosphate pathway. The following section focuses on faty acid synthesis. Asignment: Nelson & Cox, pp. 805 - 814 (stop at "Long-Chain.."). 1. Synthetic and degradative pathways often utilize diferent pathways a. Give at least two examples of the fact that synthetic and degradative pathways are not simply reversals of one another. b. Why is this fact important in biological systems? 2. The formation of malonyl CoA from acetyl CoA and bicarbonate is the rate- limiting step in faty acid biosynthesis (Fig. 21-1, p. 806). a. Write, with structures, the reaction which represents the activation of acetyl CoA. Draw a line connecting the two carbon atoms that are joined in this reaction. b. What enzyme catalyzes the conversion of acetyl CoA to malonyl CoA? c. What prosthetic group is involved in this reaction? Discuss the role of the prosthetic group (Note its role is the same as in pyruvate carboxylase, Fig. 16-16, p. 634). What compound is required before the carboxyl group from HCO 3 - can be transfered to biotin? Unit 14 4 3. Use Fig. 21-2 (p. 807) to show the four-step sequence that lengthens a growing faty acyl chain by two carbons. a. Point out the condensation step in this pathway. 1) HCO 3 - is an important player in faty acid biosynthesis. Does the carbon from HCO 3 - become incorporated into the faty acid backbone (p. 809)? 2) Why do cels go to the trouble of adding CO 2 to make a malonyl group from an acetyl group, only to lose CO 2 again during the formation of faty acids (p. 809)? 3) Write balanced chemical equations for a similar carboxylation / decarboxylation sequence in gluconeogenesis? b. What type of reaction is involved in each of the subsequent steps (p. 809)? 1) How does this series of reactions compare with the series of reactions in the ?-Oxidation of faty acids? 2) An important generalization in metabolism is that NADH is generated in degradative reactions and NADPH is utilized in biosynthetic reactions. Does this generalization hold true for faty acid degradation and synthesis? 3) In general, degradative pathways generate ATP and biosynthetic pathways consume ATP. In which step(s) in faty acid synthesis is (are) ATP utilized (Fig. 21-1, p. 806)? Unit 14 5 4. Use Figs. 21-4 (p. 808), 21-6 (p. 810), and 21-7 (p. 811) to describe the overal proces of palmitate synthesis. a. How many molecules of malonyl CoA are required to synthesize a 16 carbon faty acid chain? b. How many NADPHs are required for the synthesis of the palmitate? c. Write a balanced equation for the net reaction for palmitate synthesis (equation 21-3, p. 811; Note there are only six waters in the net reaction because one of the seven is used to cleave the completed faty acid product from the enzyme). d. What two- or thre-carbon compound gives rise to each numbered section shown in the palmitate molecule below? When a cel extract is incubated in the presence of malonyl CoA, faty acids are synthesized. You have made thre diferent preparations of malonyl CoA each with a diferent radioactive carbon atom. Thre diferent faty acid synthesis reactions are then set up. For each, mark the atoms that wil be radioactively labeled in the faty acid structure below. H C-CH -CH -CH -CH -CH -CH -CH -CH -CH -CH -CH -CH -CH -CH -C-O 22 O 3 2 2 2222 222 222 - 1 2 3 4 5 6 7 8 5. Acetate is shuttled out of mitochondria as citrate. a. Use Fig. 21-10 (p. 813) to describe how acetyl CoA is translocated from the inside of the mitochondrion to the cytosol, and how NADPH can be generated in the proces. b. How many NADPH are needed to synthesize one molecule of palmitate? How many NADPH can be generated as a result of this transport cycle? Does the NADPH generated in this cycle suffice for faty acid synthesis? If not, from which pathway does the remainder come (Fig. 21-9, p. 812)? Unit 14 6 6. Faty acid synthesis is highly regulated (p. 814). a. What enzyme in faty acid synthesis is the rate-limiting step and is therefore an important site of regulation? b. In vertebrates, what compound acts as an alosteric fedback inhibitor? What compound is an alosteric activator (Fig. 21-11, p. 814)? c. Discuss how this enzyme is also regulated by hormone regulated covalent modification (p. 814). d. Discuss the role of fructose 2,6-bisphosphate acumulation in alowing exces carbohydrate to be converted to fat (Figs. 15-16 [p. 587] and 15-17 [p. 588]). To answer this question, think about the regulation of glycolysis in terms of celular energy and the need to run through glycolysis to convert exces carbohydrate to faty acid. System Administrator Microsoft Word - U14_F08.doc
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