NAME KEY ID # 1 EXAM 4 BIOC 460 Wednesday May 8, 2002 Please include your name and ID# on each page.NAME KEY ID # 2 1. (5 pts.) What carbohydrate molecule is common to both the glycogen phosphorylase and glycogen synthetase reactions? Glucose 1-phosphate is one of the products of the phosphorylase reaction and also a substrate in the glycogen synthase reaction. 2. (5 pts). How many ATPs are produced per mole of glucose by aerobic metabolism in muscle cells if the glucose is derived from dietary sources versus glucose produced by glycogen phosphorolysis? Explain. Dietary glucose must be phosphorylated by hexokinase to produce glucose-6-phosphate, a substrate in glycolysis. This reaction requires an investment of 1 ATP. The total yield of ATP from dietary glucose is 30. In contrast, the isomerization reaction converting glucose-1-phosphate to glucose-6-phosphate bypasses the requirement for ATP hydrolysis, and therefore, glucose units produced by the glycogen phosphorylase reaction yield a total of 31 ATP by aerobic metabolism. 3. von Gierke's disease is one of several human glycogen storage diseases that are caused by enzyme deficiencies in glycogen metabolism. a. (5pts.) What is the biochemical basis of von Gierke's disease? What is the rationale for corn starch therapy every four hours as a treatment for von Gierke's disease? The biochemical basis for von Gierke's disease is a deficiency in the enzyme glucose-6-phosphatase. Since individuals with this disease cannot regulate blood glucose levels through liver glycogen metabolism, they must be fed glucose on a regular basis to maintain a safe level in the blood [corn starch is used as a source of glucose]. b. (5pts.) Why would individuals with von Gierke's disease release a small amount of glucose into the blood after injection with a high dose of glucagon? Glucagon stimulates glycogen breakdown, and the product of debranching enzyme is free glucose, which is released into the blood (~10% of available glucose in glycogen is contained in alpha-1,6 branch points).NAME KEY ID # 3 4. (10 pts.) Make a table showing how the complete oxidation of one mole of palmitate yields 106 ATP. Include in your table the names of the pathways involved at each stage and the total amount of acetyl CoA, NADH, FADH2 and GTP produced. - Generation of palmitoyl-CoA from palmitate: - 2ATP - Fatty acid oxidation: Palmitoyl CoA + 7 FAD + 7 NAD + 7 CoA + 7 H2O ---> 8 acetyl CoA + 7 FADH2 + 7 NADH + 7H - Citric Acid Cycle; 8 acetyl CoA = 24 NADH + 8 FADH2 + 8 ATP (from GTP) - Oxidative phosphorylation; 31 NADH = 31 x 2.5 ATP = 77.5 ATP 15 FADH2 = 15 x 1.5 ATP = 22.5 ATP TOTAL: 106 ATP 5. (5 pts.) Glucagon signaling inhibits acetyl CoA carboxylase activity through phosphorylation, whereas, insulin signaling stimulates acetyl CoA carboxylase activity by dephosphorylation. Explain the metabolic logic of this regulation in terms of the functions of acetyl CoA carboxylase, glucagon and insulin. Acetyl CoA carboxylase is the key regulated enzyme in fatty acid synthesis. Glucagon is the "hunger hormone" and signals low blood glucose levels. Turning off fatty acid synthesis makes sense because glucose units should be exported to the blood not metabolized by glycolysis to produce more acetyl CoA. Insulin signals high glucose levels in the blood and therefore it makes sense to stimulate fatty acid synthesis by activating the enzyme acetyl CoA carboxylase. 6. (5 pts.) What is the biochemical basis for improved anti-inflammatory action and reduced stomach bleeding in individuals who use Celebrex compared to aspirin? COX-1 is an enzyme that protects the stomach lining from damage. COX-2 is a enzyme involved in inflammation and is responsible for clinical symptoms. Celebrex is COX-2 specific inhibitor that has a high affinity for the active site of COX-2, but is too large to bind to COX-1. Aspirin is a relatively small molecule that binds to the active sites of both COX-1 and COX-2. Aspirin is a less effective anti-inflammatory agent because of its low affinity for COX-2 and it also has the associated side effect of stomach bleeding due to inhibition of COX-1.NAME KEY ID # 4 7. (5 pts.) What is the biochemical basis for Tay Sachs disease and why is it rare today as compared to 50 years ago? Tay Sachs disease is a neurological disorder caused by a deficiency in an enzyme required for sphingolipid metabolism. The disease phenotype is caused by a build-up of the ganglioside GM2 substrate which is not degraded. Tay Sachs disease is rare today because of prenatal diagnosis which is able to detect fetuses with the disease prior to birth and genetic pre-screening is used to identify prospective parents as Tay Sachs carriers with counseling to asses risks. 8. (5 pts.) In addition to limiting dietary intake of cholesterol, describe two different treatments that have been used to lower serum cholesterol levels. Bile salt resins are ingested which bind to bile salts in the intestine and result in the removal of bile salts from the body. This treatment lowers cholesterol levels because the available cholesterol is converted to bile salts to replace what was lost. HMG CoA Reductase enzyme inhibitors which block the first commitment step in de novo cholesterol biosynthesis. 9. (5 pts.) What explains the developmental progression from feminization to masculinization at puberty in males with a 5-alpha-reductase deficiency? The enzyme 5-alpha-reductase is required to convert testosterone to dihydrotestosterone (DHT) which is a more potent androgenic hormone. A deficiency in this enzyme causes testicular feminization in young boys because they lack sufficient levels of DHT to promote complete development of male reproductive organs. However at puberty, sufficient amounts of testosterone are produced by the underdeveloped testes to result in an androgen surge thus promote masculinization. 10. (5 pts) Why does treatment with the steroid antagonist tamoxifen block estrogen signaling in breast cancer cells but not inhibit gluconeogenesis in the liver? Tamoxifen is an estrogen antagonist that binds with high affinity to the estrogen receptor and blocks estrogen signaling in breast cancer cells. Tamoxifen does not bind to the glucocorticoid receptor which controls gluconeogenesis in the liver.NAME KEY
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