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Transcript
NST 103 Spring 2006 Name Midterm III (4 pages, 100 pts), April 6, 2006 SID ____ I. (@2pts ea = 10 pts) Choose the SINGLE best answer to each question. i) Which pathway is NOT likely to be active in the fasting state? A. De novo lipogenesis B. Gluconeogenesis C. Urea cycle D. Catabolism of amino acid carbon skeletons E. None of the above Answer __A____ ii) The activity of which enzyme is not influenced by its phosphorylation? A. Acetyl-CoA carboxylase B. Hexokinase C. Glycogen synthase D. Phosphofructo kinase-2 E. Pyruvate kinase Answer __B____ iii) Which of the following takes place in mitochondria? A. Citrate degradation to yield acetyl-CoA B. Formation of malonyl CoA C. Glucose-6-phosphatase reaction D. Carbamoyl phosphate synthesis E. Synthesis of urea Answer __D____ iv) Which of the following links the TCA and urea cycles? A. Malate B. Arginine C. Alpha-ketoglutarate D. Fumarate E. None of the above Answer __D____ v) Activation of FFA requires energy equivalent to A. 0 ATP B. 1 ATP C. 2 ATP D. 3 ATP E. 4 ATP II. (12 pts) Fill in the blank with the appropriate word or phrase. Answer __C____ -ketoglutarate -keto acid for glutamate pyruvate -keto acid for alanine malonylCoA A molecule that inhibits CPT1 (carnitine palmitoyl transferase 1) 6 Number of -oxidation cycles required to oxidize a 14C FA 1 Marasmus Disease due to inadequate protein and energy Ornithine or NH3 Availability of this molecule determines the rate at which urea is synthesized Citrate An allosteric activator of acetyl-CoA carboxylase Malonyl CoA This molecule donates 2 carbons during each round of fatty acid synthesis AcetylCoA, OAA This molecule is one product of the ATP-citrate lyase reaction (other than ADP) Pantothenic acid Micronutrient essential to make acyl-carrier protein and CoA AcetylCoA Compound that builds up in mitochondria during excess energy intake that cannot cross the mitochondrial membrane The compound that activate flux through the pentose phosphate pathway NADP III. (8 pts) Match the enzymes on the left to their definitions on the right. a) PEPCK b) Glucose-6-phosphatase c) FBP-1 d) FBP-2 e) PFK-1 f) PFK-2 g) Pyruvate carboxylase h) Pyruvate kinase __f__ __d__ __e__ __c__ __a__ __b__ __h__ __g__ Synthesizes fructose-2,6-bis-phosphate Degrades fructose-2,6-bis-phosphate Stimulated by fructose-2,6-bis-phosphate Inhibited by fructose-2,6-bis-phosphate Its mRNA level is increased by glucagon Catalyzes last step in gluconeogenesis Glycolytic enzyme bypassed by 2 gluconeogenic enzymes Gluconeogenic enzyme that requires biotin IV. (24 pts) State whether each of the following statements is TRUE or FALSE, and briefly explain why. 1. All steps in palmitate synthesis, other than activation of acetyl-CoA, occur on the acyl-carrier protein of the fatty acid synthase complex. TRUE, 2. Glycerol can be used for gluconeogenesis in the liver, muscle, and adipose tissues. FALSE. GNG can’t occur in the muscle because it lacks glucose-6-phosphatase. GNG from glycerol can’t occur in the adipose tissue because it lacks glycerol kinase 3. If a person excluded cholesterol from his/her diet, the HMGCoA reductase gene would be upregulated. TRUE, since HGMCoA reductase is inhibited by cholesterol regardless of whether this cholesterol is newly synthesized or delivered via the diet. Reducing cholesterol intake will remove any feedback inhibition effect that dietary cholesterol would have on this enzyme. 2 4. Increasing the rate at which a protein is synthesized will increase the amount of that protein in the body. FALSE degradation also needs to be considered. A change in protein level is the NET result of synthesis and degradation. 5. Ketone bodies are synthesized in the adipose tissue from dietary fatty acids. FALSE KB’s are synthesized primarily in liver, not in adipose. KB are synthesized when acetyl CoA supply in mitochondria exceeds the energy need of that cell. While dietary fatty acids might be used to synthesize KB by liver (in low-carbohydrate, low insulin diet situation), dietary fatty acids would be incorporated into new TAG in adipose. 6. The body requires a large amount of glucose to meet the requirement for NADPH. FALSE. Reducing equivalents in the form of NADPH are generated primarily via the PPP. Although glucose is the substrate for the PPP, the carbon skeletons are largely recycled back to glucose via glycolysis then GNG. This spares glucose, greatly diminishing the need for glucose molecules for this pathway. V. (30 pts) Provide brief answers to the following questions: a. Why would gluconeogenesis from alanine require increased transport of malate across the mitochondrial membrane, whereas gluconeogenesis from lactate would not. The conversion of lactate to pyruvate in the cytosol generates an NADH molecule from NAD.. If alanine is transaminated in the mitochondria rather than in the cytosol, the pyruvate molecule can be converted to OAA which, in turn, can be reduced to malate which is transported across the mitochondrial membrane. In the cytosol, malate can be oxidized to OAA, releasing the reducing equivalent in the form of NADH. This NADH can then be utilized for GNG. b. Why is the Pentose Phosphate Pathway required for synthesis of fatty acids? It produces NADPH which is necessary for Fatty Acid Synthesis c. Describe the significance of PALP and the role of Schiff bases in this significance? PALP is a cofactor in transamination reactions (other types also may be acceptable) that are central to metabolism of protein and amino acids. The amino acid can bind to PALP via a Schiff base. d. Why does fatty acid catabolism not lead to net gluconeogenesis? Would result in depletion of TCA intermediates 3 e. What is the most immediate fate of the carbon and N components of the aspartate molecule that enters the urea cycle? Cfumarate Nurea f. Why are the kidneys, and not the liver, the preferred organ for net synthesis of arginine? The kidneys can export arginine without compromising their metabolic capability whereas the ability of the liver to synthesize urea would be compromised since exporting arginine could deplete the liver of the ornithine molecules needed to accept N in the form of carbamoyl P. VI. (12 pts) .The following questions pertain to a situation in which a person is consuming a highprotein and low-carbohydrate diet. a. Assuming that the person is in energy balance, is there likely to be gluconeogenesis? Why or why not? Yes, because glucagon will stimulate GNG and because the low carbohydrate content of the diet may not provide sufficient glucose to meet the needs of the obligatorily glycolytic tissues. b. Assuming that the person is in positive energy balance, will there be weight gain or loss? Identify a pathway that will be predominantly responsible for the weight change, and indicate what will be the substrates and products. Weight gain. (only one of the following pathways need be described for full points) De novo lipogenesis; substrates are amino acid carbon skeletons into acetyl-CoA (rather than from glucose, given a low carbohydrate diet), products are fatty acids or TAG. Protein synthesis, substrates are amino acids, products are newly synthesized proteins. c. In comparison to a person on a high-carbohydrate and low-protein diet (both in energy balance), will the person on the high-protein diet excrete more or less urea? Explain. More urea, because excess dietary amino acids will be catabolized, and the nitrogen needs to be disposed of via urea VIII. (4 pts) Describe 2 types of reactions that can be used to remove the N from a glutamine molecule. Provide the names of the substrates, products and enzymes for each, and classify using the following terms. deamination, transamination, deamidation, and transamidation. Deamination- GlutamineGlutamate + NH3 via enzyme glutaminase Glutamate a-ketoglutarate + NH3 via enzyme glutamate dehydrogenase Transamidation- Glutamine + PRPP glutamate + phosphoribosyl amine via enzyme glutamylamidotransferase Tranamination – glutamate + a-ketoacid a-ketoglutarate + amino acid via a transaminase (providing a specific enzyme such as alanine aminotransferase or aspartate aminotransferase is great) 4