Section 1: Electron Transport and Oxidative...

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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. An increase in the rate of this pathway would cause a decrease in [ADP] B. An increase in the rate of this pathway would cause a parallel decrease in the rate of fuel oxidation C. An increase in the rate of this pathway would require an increased supply of NAD D. The conversion of A & B to X & Y would be a catabolic pathway E. Either X or Y must be a macromolecule. 2. Which of the following statements about ATP is TRUE? A. A solution of ATP at room temperature will spontaneously hydrolyse to give ADP and phosphate B. The turnover of ATP (ie, the total amount that gets degraded and recreated per day) is about 50 g C. During times of need, ATP can be produced by one tissue and transported through the bloodstream to other tissues D. ATP can be stored in Golgi membrane vesicles for use during periods of high energy demand. E. The total concentration of adenine nucleotides in a healthy cell (ie, [ADP] + [ATP] + [AMP] is always about 4- 6 mM. 3. 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. The generation of ATP in the cytoplasm

Transcript of Section 1: Electron Transport and Oxidative...

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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. An increase in the rate of this pathway would cause a decrease in [ADP]B. An increase in the rate of this pathway would cause a parallel decrease in the rate of

fuel oxidationC. An increase in the rate of this pathway would require an increased supply of NADD. The conversion of A & B to X & Y would be a catabolic pathwayE. Either X or Y must be a macromolecule.

2. Which of the following statements about ATP is TRUE?

A. A solution of ATP at room temperature will spontaneously hydrolyse to give ADP and phosphate

B. The turnover of ATP (ie, the total amount that gets degraded and recreated per day) is about 50 g

C. During times of need, ATP can be produced by one tissue and transported through the bloodstream to other tissues

D. ATP can be stored in Golgi membrane vesicles for use during periods of high energy demand.

E. The total concentration of adenine nucleotides in a healthy cell (ie, [ADP] + [ATP] + [AMP] is always about 4-6 mM.

3. 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 mitochondriaB. The generation of ATP in the cytoplasmC. Trapping through the addition of polar residues after transport from the blood into the

cytoplasmD. A dependence on the availability of NADE. The net production of water during the whole process

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4. Which statement regarding the macromolecular fuel stores is FALSE?

A. Glycogen, but not fat, is stored in association with waterB. One gram of fat releases over twice as much energy than the same amount of glycogenC. The total mass of fat in the human body is about 1000-fold higher than that the total

mass of body glycogenD. If all our energy was stored as glycogen, we would weigh at least 40 kg more than we

do nowE. Fat, but not glycogen, can be transported from liver to other tissues

5. Which one of the following rules/relationships is INCORRECT?

A. ADP is used when protons flow through the F0F1ATPase B. Proton re-entry into the matrix and ATP synthesis must occur simultaneouslyC. A molecule of ATP is formed each time a proton is pumped out of the matrix D. NADH cannot give hydrogens directly to oxygenE. 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. The availability of glucoseB. The availability of NADHC. The availability of acetyl CoAD. The availability of ADPE. The availability of fatty acids

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Use the options below to answer questions 7 to 10

The adipocytes were treated separately with each of the compounds below.

A. Rotenone: an inhibitor of electron transport within Complex IB. Noradrenalin: an activator of the beta-3 receptors on brown adipocytesC. Methylene Blue: an acceptor of electrons from cytochrome cD. Fluoroacetate: an inhibitor of the Kreb’s CycleE. 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. In each Complex there are proteins which have electron or hydrogen-carrying prosthetic groups

B. The Complexes are free to move laterally in the inner mitochondrial membraneC. Some Complexes span the membraneD. In some redox reactions in the chain, protons are consumedE. The inter-complex carriers ubiquinione and cytochrome c carry hydrogens and

electrons, respectively

12. As a check on the scanning procedure enter an answer of A to question 12 on the answer sheet.

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13. Which statement regarding the F0F1ATPase is INCORRECT?

A. The flow of protons through F0 is required to turn the gamma-subunit.B. The alpha- and beta-subunits of F1 DO NOT rotate as protons enter the matrix.C. The F1 portion is located on the matrix face of the inner mitochondrial membrane.D. ATP is made by the gamma-subunits.E. About three protons are required to make one ATP

14. Which statement regarding leptin is INCORRECT?

A. Obese individuals are relatively resistant to the actions of leptinB. Leptin increases energy expenditure in rodents but not so much in humansC. Leptin is secreted by the alpha-cells of the pancreas after a mealD. A lack of leptin induces hyperphagiaE. Blood leptin levels are generally higher in obese individuals

15. Which statement about Basal Metabolic Rate (BMR) is CORRECT?

A. BMR never comprises more than 30% of whole body energy expenditureB. BMR refers to the energy used as a consequence of GLUT-1 catalysed glucose

metabolismC. BMR is the average daily amount of energy expended by a standard 70 kg person at

20oC D. BMR is decreased in response to thyroid hormoneE. BMR is lower in obese subjects than in lean subjects of the same weight

16. Which of the following statements regarding the Glycemic Index (GI) is CORRECT?

A. Amylose starch has a higher GI than amylopectin starchB. Sucrose does not have a GI because it is a disaccharide containing fructoseC. It is not practical to measure the GI of foods containing less than 1% (w/w)

carbohydrate D. The GI of lactose is 100E. High GI foods often cause flatulence

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Opposite is the structure of glucose presented as a Haworth projection. Consider this structure, and the structures (A – E), when answering Questions 17-18

17. Which structure (A – E) is a keto sugar?

18. Which structure (A – E) is the non-enzymic product of -D-glucose in solution?

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?

OH

OH

OH

H

H

OHH

OH

CH2OH

H

beta-D-glucose

CH2OH

OHCH2OH

OH

OHO

OOH

H

OH

H

H

OHH

OH

CH2OH

OH

OH

H

OH

H

OHH

OH

CH2OH

H

OHCH2OH

OH OH

O

OH

OH

OH

H

H

OHH

OH

CH2OPO3H

H

A B

C D

E

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A. The skin, red blood cells and kidney have an obligatory requirement for glucoseB. The extent of protein glycosylation is directly proportional to time of exposure to

glucoseC. The glycosylation of proteins is a non-enzymatically controlled reactionD. Glucose is a relatively reactive moleculeE. The brain does not possess GLUT-4 transporters: it only has GLUT-1 transporters.

20. Which of the following does NOT have a free anomeric carbon atom?

A. AmyloseB. SucroseC. MaltoseD. LactoseE. Cellulose

21. Glucose uptake into tissues following a carbohydrate meal is facilitated by:

A. an increased number of GLUT-2 transporters on the muscle cell surfaceB. a loss of GLUT-4 transporters from the muscle Golgi apparatusC. insulin-stimulation of glucose uptake into the liver D. an increase in GLUT-1 expression in brain cellsE. rapid trapping of glucose in muscle cells by glucokinase

22. Which of the following properties is NOT a feature of a typical rate limiting enzyme and/or flux generating step?

A. The step is irreversibleB. The concentration of the substrate is very much greater than the Km of the enzymeC. The enzyme operates under Vmax conditionsD. The activity of the enzyme can be regulated by changes in gene expressionE. The enzyme is regulated by the concentration of substrate alone

23. As a check on the scanning procedure enter an answer of A to question 23 on the answer sheet.

24. Which statement regarding the conversion of glucose to glycogen in muscle is CORRECT?

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A. Glycogenesis is stimulated by phosphorylation of glycogen synthaseB. NADPH is required for the conversion of glucose 6-phosphate to glycogenC. Insulin directly stimulates phosphofructokinase to provide ATP for glycogenesisD. The consumption of ATP during glycogenesis results in an increased flux through

glycolysisE. A new molecule of glycogenin is required each time a branch point is made in the

growing glycogen chain.

25. Which statement regarding the disposal of glucose by liver and muscle is INCORRECT?

A. Insulin is essential for glycogen synthesis in muscle, but not liverB. The concentration of glucose 6-phosphate can rise high enough in liver to stimulate

glycogen synthase, but this does not happen in muscleC. A build up of glucose 6-phosphate inhibits further glucose trapping in muscle, but not

liver D. In liver, but not muscle, glucose is only made into glucose 6-phosphate if it is going to

be made into glycogen. E. The intracellular [glucose] is always equal to blood [glucose] in liver cells, but not

muscle cells

26. Which of the following changes DOES NOT occur during lipogenesis (the conversion of glucose to fatty acids)?

A. The polymerization of acetyl CoA carboxylase (ACC) increasesB. The production of malonyl CoA increasesC. The cleavage of citrate in the cytoplasm decreasesD. The consumption of NADPH increasesE. The consumption of ATP increases

27. 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-CoAmalonyl CoA

A. On the odd numbered carbons of palmitateB. None of the carbon atoms in palmitateC. On the carboxyl carbon (carbon 1) of palmitateD. On the even numbered carbons of palmitateE. On the omega-carbon (carbon 16) of palmitate

The following information refers to Questions 28-29.

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The following enzymes (A – E) are all involved in the synthesis of fatty acids from glucose.

A. Glucose 6-phosphate dehydrogenaseB. ATP citrate lyaseC. Acetyl CoA carboxylaseD. Pyruvate dehydrogenaseE. 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. Hydration of a double bonded carbonB. Reduction of a ketone (C=O) to an alcohol (C-OH)C. CarboxylationD. DecarboxylationE. Reduction of a double bonded carbon (-CH=CH-)

31. Which of the following statements regarding fat digestion is INCORRECT?

A. Triglyceride is not soluble in waterB. Bile salts are made in the liver but stored in the gall bladderC. Bile salt production involves adding polar residues on to cholesterolD. Lipoprotein lipase, attached to the inside of the gut wall, hydrolyses dietary fatE. The hydrolysis products of fat are re-esterified back to lipid by the intestinal cells

before export into the blood stream.

32. 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. In both people, there would be little rise in level of chylomicrons in the blood stream after a meal.

B. Both people would experience flatulenceC. The faeces of both individuals would be relatively buoyantD. Fat soluble vitamin uptake would be compromised in both subjects.E. Bile salts would not be produced in either person.

33. Which of the following is NOT a fate of cholesterol in mammalian tissues?

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A. Acetyl CoAB. Incorporation into VLDL. C. Incorporation into plasma membranesD. Cholesterol estersE. Steroid hormones

34. Dietary cholesterol is transported from the liver:

A. On carnitineB. In chylomicronsC. In HDLsD. Freely dissolved in solution without attachment to a carrier.E. In VLDLs

35. Ketone bodies are transported to tissues:

A. Freely dissolved in solution without attachment to a carrier.B. In chylomicronsC. On carnitineD. In HDLsE. In VLDLs

36. An inhibitor of the interaction of VLDL with target tissues would:

A. Inhibit the uptake of dietary fat in the intestineB. Inhibit the transport of fat from the liver to the tissuesC. Increase the production of LDLs in the bloodstreamD. Inhibit the release of fatty acids from adipose tissueE. Increase the uptake of dietary cholesterol by cells from LDLs

37. 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. Increasing the consumption of omega-3 fatty acids.B. Reducing the intake of meat and dairy productsC. Treatment with resins that block bile salt reabsorbtionD. Treatment with statins E. Ingesting sterols of plant originUse graphs (A – E) to answer Questions (38-40)

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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).

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?

41. The graph below does NOT represent:

A

0

20

40

60

80

100

120

0 0.5 1 1.5 2 2.5 3

Time (days)

% A

ctiv

ity/

conc

entra

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B

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% A

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% A

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D

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% A

ctiv

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conc

entra

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E

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% A

ctiv

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conc

entra

tion

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0

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120

0 0.5 1 1.5 2 2.5 3

Time (days)

% A

ctiv

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once

ntra

tion

A. The rate of glucose output from the liverB. The liver glycogen contentC. The activity of muscle pyruvate dehydrogenaseD. The blood insulin levelE. The intracellular liver concentration of fructose 2,6 bisphosphate

42. Which statement regarding the stimulation of glycogenolysis during starvation is INCORRECT?

A. Phosphorylase kinase phosphorylates phosphorylaseB. cAMP-dependent kinase is not activated by phosphorylationC. One phosphorylase molecule is activated for every one glucagon molecule that binds to

a liver glucagon receptorD. Glucagon does not stimulate a rise in [cAMP] in muscleE. Muscle cannot convert glucose 6-phosphate into glucose for release into the blood

stream.

43. Which statement regarding white adipose tissue after three days of starvation is CORRECT:

A. Phosphodiesterase will be fully activeB. Hormone sensitive lipase will be phosphorylatedC. The release of fatty acids into the blood stream will be decreasing relative to day oneD. The rate of glycerol release is enough to sustain the production of 120 of glucose per

dayE. cAMP-dependent protein kinase will be inhibited

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44. Which of the following statements regarding our fuel stores is INCORRECT?

A. In the early post-absorbtive period, the brain uses about 120g of glucose per dayB. Fatty acids are released once all body glycogen stores have been used upC. Although we store most of our energy as fat, we cannot convert fatty acids into

carbohydrateD. Net gluconeogenesis is possible from part of triacylglycerolE. The brain cannot use fatty acids as they do not pass across the blood-brain barrier.

45. The Cori-Cycle to operates when:

A. liver phosphoenolpyruvate carboxykinase is activatedB. liver pyruvate carboxylase is inhibitedC. muscle beta-oxidation is inhibitedD. glucose transport into muscles is preventedE. muscle pyruvate dehydrogenase is stimulated

46. Which statement regarding the process of beta-oxidation is CORRECT?

A. The transport of fatty acids into the cell is totally dependent on a membrane carrierB. The movement of fatty acids into the mitochondrial matrix is stimulated by malonyl

CoAC. The beta-oxidation of a 16-carbon fatty acyl CoA would result in the production of 8

FADH2 and 8 NADH moleculesD. Matrix carnitine and cytosolic carnitine pools cannot mixE. The coupling of fatty acids to Coenzyme A involves consumption of ATP

47. As a check on the scanning procedure enter an answer of A to question 47 on the answer sheet.

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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 Ebeta-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. Deamination to produce carbon skeletonsB. Conversion to glucose in the liverC. Synthesis of new proteinD. Conversion to fat in the liverE. Conversion to alanine in the muscle and storage as poly-alanine

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53. For a 60 kg female which of the follow type of protein intake would be LEAST desirable?

A. 240 g/day of protein comprised of all amino acidsB. 60 g/day of protein comprisedof a all amino acidsC. 120 g/day of protein deficient in lysineD. 120 g/day of protein deficient in alanineE. 60 d/day of protein deficient in both alanine and glutamate

54. Which statement regarding the Krebs Cycle is CORRECT?

A. Complete oxidation of one acetyl CoA in the Krebs Cycle produces 4 NADH and 1 FADH2

B. The major rate limiting steps are the reactions from succinate to oxaloacetateC. The sequence of reactions from succinate to oxaloacetate are similar to those involved

in fatty acid sythesisD. The Krebs Cycle does not produce any ATP directlyE. 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.

55. Which of the following statements about protein folding in the ER is correct?

A. The hydrophobic signal peptide is buried in the core of the protein as it folds.B. The reducing environment inside the ER ensures rapid formation of disulfide bonds in

proteins undergoing folding.C. Peptidyl disulfide isomerase forms covalent bonds with substrate proteins.D. ATP hydrolysis catalysed by the signal recognition particle is used to drive protein

folding.E. UDP:glucosyl transferase removes glucose residues from glycoproteins which have

folded correctly

56. During biosynthesis of glycosylphosphatidylinositol (GPI) -anchored proteins:

A. The GPI anchor becomes covalently linked to the S atom of a cysteine residue on the protein.

B. Dolichol phosphate is displaced by the GPI anchor in a transesterification reaction.C. Inositol triphosphate is released and then acts to mobilise Ca2+ from intra-cellular

stores.D. Glucose residues are trimmed from the GPI anchor.E. The GPI anchor is linked to the C-terminal of the protein in a transamidation reaction.

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57. A common structural theme in the cytokine family of receptors is:

A. They all contain seven strands of beta-sheet which span the cell membrane.B. They all mediate signal transduction through G-protein coupled events.C. Their extra-cellular domains are alpha-helical bundles.D. They are all GPI-anchored proteins.E. Typically, binding of cytokines to their receptors leads to dissociation of the receptors

into their active monomeric forms

58. Binding of a cytokine to a cytokine receptor would be generally expected to lead to:

A. An influx of Ca2+ through activation of a ligand-gated ion channel.B. Translocation of the receptor:cytokine complex to the nucleus. C. Autophosphorylation of a tyrosine kinase bound to the receptor.D. Dissociation of the receptor from a dimer to a monomer form.E. Inhibition of intra-cellular adenyl cyclase.

59. Which of the following statements about the JAK-STAT signalling pathway is correct?

A. Dephosphorylation of a JAK kinase allows the binding of a STAT transcription factor, mediated by its SH2 domains.

B. JAK kinases use GTP to phosphorylate small GTP-binding proteins such as Ras.C. Phosphorylation of STAT proteins allows them to dimerise through their SH2 domains.D. JAK-dependent phosphorylation of calmodulin leads to inhibition of Ca2+-dependent

protein kinases.E. Entry of JAK kinases to the nucleus is followed by phosphorylation of the 2’ OH

groups of the deoxyribose residues of chromosomal DNA.

60. In general, binding of growth factors to receptors with intra-cellular tyrosine kinase domains might be expected to:

A. Lead to tyrosine kinase-catalysed dephosphorylation of phosphoproteins.B. Lead to activation of the Ras protein kinase through the action of the Raf adaptor

protein.C. Lead to the activation of protein kinase C because of decreased levels of intra-cellular

Ca2+.D. Culminate in the phosphorylation of transcription factors by a MAP kinase.E. Lead to enhanced expression of protein kinase A.

61. As a check on the scanning procedure enter an answer of A to question 61 on the answer sheet.

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62. During activation of protein kinase C:

A. An influx of Ca2+ from the nucleus to the cytoplasm leads to conversion of protein kinase C into its active form.

B. Production of IP3 leads to the opening of a ligand-gated ion channel in the membrane of the endoplasmic reticulum.

C. Protein kinase C enters the nucleus after a steroid hormone binds to itD. Calmodulin-activated protein kinase binds to the IP3 receptor through its SH2 domain.E. Diacyl glycerol is phosphorylated and becomes incorporated into the cell membrane.

63. One of the characteristic features of G-protein coupled receptors is:

A. Their primary role is signal transduction within cells of the immune system.B. Normally, small GTP-binding proteins like Ras bind to G-protein coupled receptors

during their activation.C. G-protein coupled receptors are heterotrimers of alpha-, beta- and gamma-chains.D. In most cases, their monomeric forms are inactive.E. They contain seven membrane-spanning alpha-helices.

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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)

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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?

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18/03A PART B: To be answered by ALL students. Page 19 of 27 pages

66. 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)

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18/03A PART B: To be answered by ALL students. Page 20 of 27 pages

67. 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

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18/03A PART B: To be answered by ALL students. Page 21 of 27 pages

68. 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

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18/03A PART B: To be answered by ALL students. Page 22 of 27 pages

Insulin Sensitivity

fasting blood [glucose] (mM)

high

low4 8 12 16

A

B C

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18/03A PART B: To be answered by ALL students. Page 23 of 27 pages

69. 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)

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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)

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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 1-phosphate (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 4-epimerase.

Galactose Galactose 1-P

Glucose 1-P

UDP-Glucose

UDP-Galactose

Galactokinase

Transferase UD-glucose-4- epimerase

Normal GlucoseMetabolism

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). 

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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)

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18/03A Part D: To be done by BCHM2902 Advanced students ONLY. Page 27 of 27 pages

THIS IS THE END OF YOUR QUESTIONS