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18/03A Semester 2, 2004 Page 1 of 27 pages PART A 1. An ANABOLIC pathway uses compounds X and Y to produces compounds A and B. Which statement is TRUE? A. B. C. D. E. 2. Which of the following statements about ATP is TRUE? A. B. C. D. E. 3. An increase in the rate of this pathway would cause a decrease in [ADP] An increase in the rate of this pathway would cause a parallel decrease in the rate of fuel oxidation An increase in the rate of this pathway would require an increased supply of NAD The conversion of A & B to X & Y would be a catabolic pathway Either X or Y must be a macromolecule. A solution of ATP at room temperature will spontaneously hydrolyse to give ADP and phosphate The turnover of ATP (ie, the total amount that gets degraded and recreated per day) is about 50 g During times of need, ATP can be produced by one tissue and transported through the bloodstream to other tissues ATP can be stored in Golgi membrane vesicles for use during periods of high energy demand. The total concentration of adenine nucleotides in a healthy cell (ie, [ADP] + [ATP] + [AMP] is always about 4-6 mM. Both fatty acids and carbohydrate can be oxidized to carbon dioxide with the concomitant consumption of oxygen. Which of the following is NOT a feature common to BOTH processes? A. The formation of acetyl CoA in the mitochondria B. C. The generation of ATP in the cytoplasm Trapping through the addition of polar residues after transport from the blood into the cytoplasm A dependence on the availability of NAD The net production of water during the whole process D. E. 18/03A 4. Page 2 of 27 pages Which statement regarding the macromolecular fuel stores is FALSE? A. B. C. D. E. 5. Semester 2, 2004 Glycogen, but not fat, is stored in association with water One gram of fat releases over twice as much energy than the same amount of glycogen The total mass of fat in the human body is about 1000-fold higher than that the total mass of body glycogen If all our energy was stored as glycogen, we would weigh at least 40 kg more than we do now Fat, but not glycogen, can be transported from liver to other tissues Which one of the following rules/relationships is INCORRECT? A. B. C. D. E. ADP is used when protons flow through the F0F1ATPase Proton re-entry into the matrix and ATP synthesis must occur simultaneously A molecule of ATP is formed each time a proton is pumped out of the matrix NADH cannot give hydrogens directly to oxygen Movement of hydrogens/electrons down the electron transport chain can only occur if protons are simultaneously being pumped from the matrix. The following information refers to Questions 6 to 10. Consider a suspension of brown adipocytes, supplied with plenty of oxygen and fuels. 6. What factor is most likely to limit the rate of fuel oxidation under these conditions? A. B. C. D. E. The availability of glucose The availability of NADH The availability of acetyl CoA The availability of ADP The availability of fatty acids 18/03A Semester 2, 2004 Page 3 of 27 pages Use the options below to answer questions 7 to 10 The adipocytes were treated separately with each of the compounds below. A. B. C. D. E. Rotenone: an inhibitor of electron transport within Complex I Noradrenalin: an activator of the beta-3 receptors on brown adipocytes Methylene Blue: an acceptor of electrons from cytochrome c Fluoroacetate: an inhibitor of the Kreb’s Cycle Oligomycin: An inhibitor of the FoF1 ATPase 7. Which compound (A - E) would result in the highest rate of oxygen consumption? 8. Which compound (A - E) would result in the highest rate of ATP synthesis? 9. Which compound (A – E) would (after a few minutes) result in the largest proton gradient (largest difference in the [H+] across the matrix membrane)? 10. Which compound (A – E) would cause both ubiquinone and cytochrome c to become fully oxidised? 11. ALL the facts listed below are features of the electron transport chain. Which feature is NOT RELEVANT to the process of proton pumping from the mitochondrial matrix? A. B. C. D. E. 12. In each Complex there are proteins which have electron or hydrogen-carrying prosthetic groups The Complexes are free to move laterally in the inner mitochondrial membrane Some Complexes span the membrane In some redox reactions in the chain, protons are consumed The inter-complex carriers ubiquinione and cytochrome c carry hydrogens and electrons, respectively As a check on the scanning procedure enter an answer of A to question 12 on the answer sheet. 18/03A 13. Obese individuals are relatively resistant to the actions of leptin Leptin increases energy expenditure in rodents but not so much in humans Leptin is secreted by the alpha-cells of the pancreas after a meal A lack of leptin induces hyperphagia Blood leptin levels are generally higher in obese individuals Which statement about Basal Metabolic Rate (BMR) is CORRECT? A. B. C. D. E. 16. The flow of protons through F0 is required to turn the gamma-subunit. The alpha- and beta-subunits of F1 DO NOT rotate as protons enter the matrix. The F1 portion is located on the matrix face of the inner mitochondrial membrane. ATP is made by the gamma-subunits. About three protons are required to make one ATP Which statement regarding leptin is INCORRECT? A. B. C. D. E. 15. Page 4 of 27 pages Which statement regarding the F0F1ATPase is INCORRECT? A. B. C. D. E. 14. Semester 2, 2004 BMR never comprises more than 30% of whole body energy expenditure BMR refers to the energy used as a consequence of GLUT-1 catalysed glucose metabolism BMR is the average daily amount of energy expended by a standard 70 kg person at 20oC BMR is decreased in response to thyroid hormone BMR is lower in obese subjects than in lean subjects of the same weight Which of the following statements regarding the Glycemic Index (GI) is CORRECT? A. B. C. D. E. Amylose starch has a higher GI than amylopectin starch Sucrose does not have a GI because it is a disaccharide containing fructose It is not practical to measure the GI of foods containing less than 1% (w/w) carbohydrate The GI of lactose is 100 High GI foods often cause flatulence Semester 2, 2004 18/03A Page 5 of 27 pages CH 2OH Opposite is the structure of glucose presented as a Haworth projection. Consider this structure, and the structures (A – E), when answering Questions 17-18 O H H OH H H OH H A B CH 2OH O OH OH OH O OH CH 2OH OH OH D CH 2OH CH 2OH O H OH H OH O H H OH OH H E CH 2OH H H OH beta-D-glucose H H C OH OH OH OH CH 2OPO3H O H H OH OH H H OH H OH OH 17. Which structure (A – E) is a keto sugar? 18. Which structure (A – E) is the non-enzymic product of -D-glucose in solution? Semester 2, 2004 18/03A 19. Which of the facts below is NOT an important reason why the concentration of blood glucose needs to be kept at approximately 5 mM? A. B. C. D. E. 20. an increased number of GLUT-2 transporters on the muscle cell surface a loss of GLUT-4 transporters from the muscle Golgi apparatus insulin-stimulation of glucose uptake into the liver an increase in GLUT-1 expression in brain cells rapid trapping of glucose in muscle cells by glucokinase Which of the following properties is NOT a feature of a typical rate limiting enzyme and/or flux generating step? A. B. C. D. E. 23. Amylose Sucrose Maltose Lactose Cellulose Glucose uptake into tissues following a carbohydrate meal is facilitated by: A. B. C. D. E. 22. The skin, red blood cells and kidney have an obligatory requirement for glucose The extent of protein glycosylation is directly proportional to time of exposure to glucose The glycosylation of proteins is a non-enzymatically controlled reaction Glucose is a relatively reactive molecule The brain does not possess GLUT-4 transporters: it only has GLUT-1 transporters. Which of the following does NOT have a free anomeric carbon atom? A. B. C. D. E. 21. Page 6 of 27 pages The step is irreversible The concentration of the substrate is very much greater than the Km of the enzyme The enzyme operates under Vmax conditions The activity of the enzyme can be regulated by changes in gene expression The enzyme is regulated by the concentration of substrate alone As a check on the scanning procedure enter an answer of A to question 23 on the answer sheet. 18/03A 24. E. C. D. E. Insulin is essential for glycogen synthesis in muscle, but not liver The concentration of glucose 6-phosphate can rise high enough in liver to stimulate glycogen synthase, but this does not happen in muscle A build up of glucose 6-phosphate inhibits further glucose trapping in muscle, but not liver In liver, but not muscle, glucose is only made into glucose 6-phosphate if it is going to be made into glycogen. The intracellular [glucose] is always equal to blood [glucose] in liver cells, but not muscle cells Which of the following changes DOES NOT occur during lipogenesis (the conversion of glucose to fatty acids)? A. B. C. D. E. 27. Glycogenesis is stimulated by phosphorylation of glycogen synthase NADPH is required for the conversion of glucose 6-phosphate to glycogen Insulin directly stimulates phosphofructokinase to provide ATP for glycogenesis The consumption of ATP during glycogenesis results in an increased flux through glycolysis A new molecule of glycogenin is required each time a branch point is made in the growing glycogen chain. Which statement regarding the disposal of glucose by liver and muscle is INCORRECT? A. B. 26. Page 7 of 27 pages Which statement regarding the conversion of glucose to glycogen in muscle is CORRECT? A. B. C. D. 25. Semester 2, 2004 The polymerization of acetyl CoA carboxylase (ACC) increases The production of malonyl CoA increases The cleavage of citrate in the cytoplasm decreases The consumption of NADPH increases The consumption of ATP increases If you added 14C malonyl CoA, labelled in the carboxylic acid carbon (see diagram below), to cells undergoing fatty acid synthesis to palmitate (C16) where would you expect to recover the label? -OO14C-CH2-CO-S-CoA malonyl CoA A. B. C. D. E. On the odd numbered carbons of palmitate None of the carbon atoms in palmitate On the carboxyl carbon (carbon 1) of palmitate On the even numbered carbons of palmitate On the omega-carbon (carbon 16) of palmitate 18/03A Semester 2, 2004 Page 8 of 27 pages The following information refers to Questions 28-29. The following enzymes (A – E) are all involved in the synthesis of fatty acids from glucose. A. B. C. D. E. Glucose 6-phosphate dehydrogenase ATP citrate lyase Acetyl CoA carboxylase Pyruvate dehydrogenase Phosphofructokinase 28. Which enzyme (A – E) is DIRECTLY regulated by the availability of NADP+? 29. Which enzyme (A – E) catalyses the step after which the products cannot be reconverted back into glucose? 30. During the synthesis of fatty acids from acetyl CoA, which type of reaction DOES NOT happen? A. B. C. D. E. 31. Which of the following statements regarding fat digestion is INCORRECT? A. B. C. D. E. 32. Hydration of a double bonded carbon Reduction of a ketone (C=O) to an alcohol (C-OH) Carboxylation Decarboxylation Reduction of a double bonded carbon (-CH=CH-) Triglyceride is not soluble in water Bile salts are made in the liver but stored in the gall bladder Bile salt production involves adding polar residues on to cholesterol Lipoprotein lipase, attached to the inside of the gut wall, hydrolyses dietary fat The hydrolysis products of fat are re-esterified back to lipid by the intestinal cells before export into the blood stream. Person A is eating a normal fat diet but taking a drug which inhibits fat digestion. Person B is eating a diet in which the fat has been replaced by Olestra. Which statement is INCORRECT? A. B. C. D. E. In both people, there would be little rise in level of chylomicrons in the blood stream after a meal. Both people would experience flatulence The faeces of both individuals would be relatively buoyant Fat soluble vitamin uptake would be compromised in both subjects. Bile salts would not be produced in either person. 18/03A Semester 2, 2004 Page 9 of 27 pages 33. Which of the following is NOT a fate of cholesterol in mammalian tissues? A. Acetyl CoA B. Incorporation into VLDL. C. Incorporation into plasma membranes D. Cholesterol esters E. Steroid hormones 34. Dietary cholesterol is transported from the liver: A. B. C. D. E. 35. Ketone bodies are transported to tissues: A. B. C. D. E. 36. Freely dissolved in solution without attachment to a carrier. In chylomicrons On carnitine In HDLs In VLDLs An inhibitor of the interaction of VLDL with target tissues would: A. B. C. D. E. 37. On carnitine In chylomicrons In HDLs Freely dissolved in solution without attachment to a carrier. In VLDLs Inhibit the uptake of dietary fat in the intestine Inhibit the transport of fat from the liver to the tissues Increase the production of LDLs in the bloodstream Inhibit the release of fatty acids from adipose tissue Increase the uptake of dietary cholesterol by cells from LDLs Below is a number of strategies used to lower serum cholesterol levels. Which strategy is designed to encourage cells to express more LDL-receptors? A. B. C. D. E. Increasing the consumption of omega-3 fatty acids. Reducing the intake of meat and dairy products Treatment with resins that block bile salt reabsorbtion Treatment with statins Ingesting sterols of plant origin Semester 2, 2004 18/03A Page 10 of 27 pages Use graphs (A – E) to answer Questions (38-40) A volunteer has starved for 3 days and a number of biochemical measurements have been made over the course of that time. Time “0” is the beginning of the post absorptive period (ie. when the last meal has been completely absorbed). A 100 80 60 40 20 100 80 60 40 20 0 0 0.5 1 1.5 2 2.5 B 120 % Activity/ concentration % Activity/ concentration 120 0 3 0 0.5 Time (days) 1.5 2 2.5 3 Time (days) C 120 120 100 100 % Activity/ concentration % Activity/ concentration 1 80 60 40 20 0 D 80 60 40 20 0 0 0.5 1 1.5 2 2.5 3 0 Time (days) 0.5 1 1.5 2 2.5 3 Time (days) E 120 % Activity/ concentration 100 80 60 40 20 0 0 0.5 1 1.5 2 2.5 3 Time (days) 38. Which graph (A – E) represents the concentration of glucose in the bloodstream? 39. Which graph (A – E) represents the blood ketone body concentration? 40. Which graph (A – E) represents the phosphorylation of liver glycogen phosphorylase? Semester 2, 2004 18/03A The graph below does NOT represent: % Activity/ concentration 41. Page 11 of 27 pages 120 100 80 60 40 20 0 0 0.5 1 1.5 2 2.5 3 Tim e (days) A. B. C. D. E. 42. Which statement regarding the stimulation of glycogenolysis during starvation is INCORRECT? A. B. C. D. E. 43. The rate of glucose output from the liver The liver glycogen content The activity of muscle pyruvate dehydrogenase The blood insulin level The intracellular liver concentration of fructose 2,6 bisphosphate Phosphorylase kinase phosphorylates phosphorylase cAMP-dependent kinase is not activated by phosphorylation One phosphorylase molecule is activated for every one glucagon molecule that binds to a liver glucagon receptor Glucagon does not stimulate a rise in [cAMP] in muscle Muscle cannot convert glucose 6-phosphate into glucose for release into the blood stream. Which statement regarding white adipose tissue after three days of starvation is CORRECT: A. B. C. D. E. Phosphodiesterase will be fully active Hormone sensitive lipase will be phosphorylated The release of fatty acids into the blood stream will be decreasing relative to day one The rate of glycerol release is enough to sustain the production of 120 of glucose per day cAMP-dependent protein kinase will be inhibited 18/03A 44. D. E. liver phosphoenolpyruvate carboxykinase is activated liver pyruvate carboxylase is inhibited muscle beta-oxidation is inhibited glucose transport into muscles is prevented muscle pyruvate dehydrogenase is stimulated Which statement regarding the process of beta-oxidation is CORRECT? A. B. C. D. E. 47. In the early post-absorbtive period, the brain uses about 120g of glucose per day Fatty acids are released once all body glycogen stores have been used up Although we store most of our energy as fat, we cannot convert fatty acids into carbohydrate Net gluconeogenesis is possible from part of triacylglycerol The brain cannot use fatty acids as they do not pass across the blood-brain barrier. The Cori-Cycle to operates when: A. B. C. D. E. 46. Page 12 of 27 pages Which of the following statements regarding our fuel stores is INCORRECT? A. B. C. 45. Semester 2, 2004 The transport of fatty acids into the cell is totally dependent on a membrane carrier The movement of fatty acids into the mitochondrial matrix is stimulated by malonyl CoA The beta-oxidation of a 16-carbon fatty acyl CoA would result in the production of 8 FADH2 and 8 NADH molecules Matrix carnitine and cytosolic carnitine pools cannot mix The coupling of fatty acids to Coenzyme A involves consumption of ATP As a check on the scanning procedure enter an answer of A to question 47 on the answer sheet. Semester 2, 2004 18/03A Page 13 of 27 pages Use the Table below to answer Questions 48-51. Options A – E show the rates of various enzymes and pathways during exercise. The scale goes from minimum (-) to maximum (+++++). Activity A B C D E beta-oxidation of fatty acids - - ++ +++ - Krebs cycle - +++ ++ ++++ - Muscle phosphorylase +++++ +++ - + +++++ Muscle - +++ - ++ ++++ - ++ - ++ - Phosphofructokinase Muscle pyruvate dehydrogenase 48. Which option (A – E) shows the pattern of fuel utilization after 30 minutes of jogging (moderate, aerobic exercise)? 49. Which option (A – E) shows the pattern of fuel utilization during a sprint? 50. Which option (A – E) shows the pattern of fuel utilization after 1 hour of running in a competitive long distance race (eg, a marathon race)? 51. Which option (A – E) is NOT possible under any exercise scenario? 52. What is NOT one of the fates of amino acids arising from the digestion of dietary protein? A. B. C. D. E. Deamination to produce carbon skeletons Conversion to glucose in the liver Synthesis of new protein Conversion to fat in the liver Conversion to alanine in the muscle and storage as poly-alanine 18/03A 53. B. C. D. E. Complete oxidation of one acetyl CoA in the Krebs Cycle produces 4 NADH and 1 FADH2 The major rate limiting steps are the reactions from succinate to oxaloacetate The sequence of reactions from succinate to oxaloacetate are similar to those involved in fatty acid sythesis The Krebs Cycle does not produce any ATP directly During one turn of the cycle, neither of the carbon atoms released as carbon dioxide have come from the acetyl CoA molecule that entered the cycle. Which of the following statements about protein folding in the ER is correct? A. B. C. D. E. 56. 240 g/day of protein comprised of all amino acids 60 g/day of protein comprisedof a all amino acids 120 g/day of protein deficient in lysine 120 g/day of protein deficient in alanine 60 d/day of protein deficient in both alanine and glutamate Which statement regarding the Krebs Cycle is CORRECT? A. 55. Page 14 of 27 pages For a 60 kg female which of the follow type of protein intake would be LEAST desirable? A. B. C. D. E. 54. Semester 2, 2004 The hydrophobic signal peptide is buried in the core of the protein as it folds. The reducing environment inside the ER ensures rapid formation of disulfide bonds in proteins undergoing folding. Peptidyl disulfide isomerase forms covalent bonds with substrate proteins. ATP hydrolysis catalysed by the signal recognition particle is used to drive protein folding. UDP:glucosyl transferase removes glucose residues from glycoproteins which have folded correctly During biosynthesis of glycosylphosphatidylinositol (GPI) -anchored proteins: A. B. C. D. E. The GPI anchor becomes covalently linked to the S atom of a cysteine residue on the protein. Dolichol phosphate is displaced by the GPI anchor in a transesterification reaction. Inositol triphosphate is released and then acts to mobilise Ca2+ from intra-cellular stores. Glucose residues are trimmed from the GPI anchor. The GPI anchor is linked to the C-terminal of the protein in a transamidation reaction. 18/03A 57. B. C. D. E. Dephosphorylation of a JAK kinase allows the binding of a STAT transcription factor, mediated by its SH2 domains. JAK kinases use GTP to phosphorylate small GTP-binding proteins such as Ras. Phosphorylation of STAT proteins allows them to dimerise through their SH2 domains. JAK-dependent phosphorylation of calmodulin leads to inhibition of Ca2+-dependent protein kinases. Entry of JAK kinases to the nucleus is followed by phosphorylation of the 2’ OH groups of the deoxyribose residues of chromosomal DNA. In general, binding of growth factors to receptors with intra-cellular tyrosine kinase domains might be expected to: A. B. C. D. E. 61. An influx of Ca2+ through activation of a ligand-gated ion channel. Translocation of the receptor:cytokine complex to the nucleus. Autophosphorylation of a tyrosine kinase bound to the receptor. Dissociation of the receptor from a dimer to a monomer form. Inhibition of intra-cellular adenyl cyclase. Which of the following statements about the JAK-STAT signalling pathway is correct? A. 60. They all contain seven strands of beta-sheet which span the cell membrane. They all mediate signal transduction through G-protein coupled events. Their extra-cellular domains are alpha-helical bundles. They are all GPI-anchored proteins. Typically, binding of cytokines to their receptors leads to dissociation of the receptors into their active monomeric forms Binding of a cytokine to a cytokine receptor would be generally expected to lead to: A. B. C. D. E. 59. Page 15 of 27 pages A common structural theme in the cytokine family of receptors is: A. B. C. D. E. 58. Semester 2, 2004 Lead to tyrosine kinase-catalysed dephosphorylation of phosphoproteins. Lead to activation of the Ras protein kinase through the action of the Raf adaptor protein. Lead to the activation of protein kinase C because of decreased levels of intra-cellular Ca2+. Culminate in the phosphorylation of transcription factors by a MAP kinase. Lead to enhanced expression of protein kinase A. As a check on the scanning procedure enter an answer of A to question 61 on the answer sheet. 18/03A 62. Page 16 of 27 pages During activation of protein kinase C: A. B. C. D. E. 63. Semester 2, 2004 An influx of Ca2+ from the nucleus to the cytoplasm leads to conversion of protein kinase C into its active form. Production of IP3 leads to the opening of a ligand-gated ion channel in the membrane of the endoplasmic reticulum. Protein kinase C enters the nucleus after a steroid hormone binds to it Calmodulin-activated protein kinase binds to the IP3 receptor through its SH2 domain. Diacyl glycerol is phosphorylated and becomes incorporated into the cell membrane. One of the characteristic features of G-protein coupled receptors is: A. B. C. D. E. Their primary role is signal transduction within cells of the immune system. Normally, small GTP-binding proteins like Ras bind to G-protein coupled receptors during their activation. G-protein coupled receptors are heterotrimers of alpha-, beta- and gamma-chains. In most cases, their monomeric forms are inactive. They contain seven membrane-spanning alpha-helices. 18/03A PART B: To be answered by ALL students. Page 17 of 27 pages Part B: Short Answer Questions to be answered by ALL students. Answer these questions in the space provided in this booklet. 64. What ways are principles and advantages/disadvantages of TWO different methods of measuring whole body energy expenditure? (5 marks) 18/03A PART B: To be answered by ALL students. Page 18 of 27 pages HINT: A sketch of the process by which lipogenesis occurs (no structures, just names!) will help you answer the questions below. (5 marks) 65. The overall, balanced equation for the synthesis of palmitate (a 16-carbon fatty acid) from glucose is: 9 glucose + 8 O2 2 palmitate + 22 CO2 + 22 H20 i) Why is there no mention of ATP or NADPH in this equation? ii) Palmitate is a highly reduced hydrocarbon chain – so why is mentioned in this equation? iii) At what steps were the carbon dioxide molecules released? iv) Roughly, what percentage of the energy in glucose is lost in doing this conversion (Mw palmitate = 256, Mw glucose = 180) v) How does lipogenesis affect the respiratory quotient? 18/03A 66. PART B: To be answered by ALL students. Page 19 of 27 pages To sustain a high rate of fatty acid oxidation in muscles it is necessary to have a large demand for ATP synthesis and a rapidly working Krebs Cycle. However, this is not the case in liver. Why? (5 marks) 18/03A 67. PART B: To be answered by ALL students. Page 20 of 27 pages The following strategies are often employed by athletes. Explain why. Justify your answers on biochemical terms but use NO MORE than one or two sentences for each strategy. (5 marks) Dietary creatine supplementation Dietary carnitine supplementation Consumption of sodium bicarbonate before a race Dietary Coenzyme Q supplementation Consumption of caffeine before a race 18/03A 68. PART B: To be answered by ALL students. Page 21 of 27 pages The insulin sensitivity and fasting blood glucose concentration of about 40 subjects was measured. The graph opposite shows the result. Each circle is a separate individual. (5 marks) i) What is the name and principle of the technique which would have been used to measure the insulin sensitivity of each individual? ii) What do THESE results tell us about the relationship between hyperglycemia and insulin resistance? iii) On a separate graph, draw the results that you would expect to see if an oral glucose tolerance test was given to individuals in each of the ‘groups’ A, B & C 18/03A PART B: To be answered by ALL students. Page 22 of 27 pages high A Insulin Sensitivity C B low 4 8 12 fasting blood [glucose] (mM) 16 18/03A 69. PART B: To be answered by ALL students. Page 23 of 27 pages Explain the molecular processes linking the binding of a growth factor to its receptor to the arrival of the transcription factor NF-B in the nucleus. *BCHM2902 students should include in their answers a discussion of the importance of ubiquitin in these processes*. (5 marks) 18/03A Part C: To be done by BCHM2002 & BCHM2102 students ONLY. Page 24 of 27 pages PART C: To be answered by BCHM2002 & BCHM2102 students ONLY. 70. i) Give an example of how a phosphorylation cascade can simultaneously inactivate and activate different target enzymes. (3 marks) ii) Briefly compare the features of phosphorylation cascades to other regulatory systems (ie, allosteric modulation and gene expression control). (3 marks) iii) PFK is not directly activated by protein kinase A dependent phosphorylation. What problems would you foresee if it was? (2 marks) 18/03A Part D: To be done by BCHM2902 Advanced students ONLY. Page 25 of 27 pages PART D: To be answered by BCHM2902 (ADVANCED) students ONLY. 71. Galactose is mainly processed by the liver. On entry into liver cells, galactose is phosphorylated by galactokinase to galactose 1-phosphate (Gal 1-P). The galactose moiety in Gal 1-P is then swapped for glucose on UDP-Glucose, giving UDP-Galactose and Glucose 1phosphate (Glu 1-P). The Glu 1-P can enter 'normal' glucose metabolic pathways, whilst UDP-Galactose can be converted into UDP-Glucose using the enzyme UDP-Glucose 4epimerase. Galactokinase Galactose Galactose 1-P UDP-Glucose UD-glucose4- epimerase Transferase Glucose 1-P UDP-Galactose Normal Glucose Metabolism In other tissues, excess galactose is converted into the dead end product galacticol by aldose reductase. A build up of galacticol in tissues, especially nerve cells, is very damaging. Two defects in galactose metabolism are known: Gdef a deficiency in galactokinase and Edef a deficiency in UDP-glucose 4-epimerase. These conditions can be identified by giving a galactose tolerance test (intravenous infusion of galactose). 18/03A Part D: To be done by BCHM2902 Advanced students ONLY. Page 26 of 27 pages i) Explain how the galactose tolerance test would help identify each condition? HINT: Consider the response of blood galactose, blood glucose and blood lactate levels in each case, and in control subjects. (5 marks) ii) What general/daily metabolic problems and/or symptoms would you expect to see in someone with each of the two conditions? (2 marks) iii) What treatment or management strategy would you recommend for each condition? (1 mark) 18/03A Part D: To be done by BCHM2902 Advanced students ONLY. THIS IS THE END OF YOUR QUESTIONS Page 27 of 27 pages