2000 - Question 2. In a person with insulin-dependent diabetes who misses two insulin injections, blood
glucose levels increase to 14mmol/L (reference range, below 8 mmol/L) Explain how
this increase in blood glucose concentration will affect water intake and excretion.
(13 minutes)


2000 - Question 3. Sarah, a 26 year old book shop manager, is at the beach, half asleep on the sand. When a
rain and hail storm hits the beach, Sarah sprints 200m over the sand to her car to escape
the storm.
(a) Outline how energy is supplied for skeletal muscle activity during Sarah’s sprint.
Indicate the likely relative contribution of pathways for providing energy, with an
explanation of your reasoning. [Mention key steps in the pathways. It is not
necessary to include all the individual reactions].
(14 minutes)
(b) Describe controls acting on or in Sarah’s skeletal muscle cells that contribute to
making substrate available for energy generation, outlining the mechanisms by
which these controls work [It is not necessary to discuss controls on subsequent
metabolism of the substrates(s)].
(13 minutes)
(c) Discuss the mechanisms which cause an increase in Sarah’s heart rate during the
(10 minutes)2000- Question 4. A healthy man is taking part in a 40 hour fast to raise money for charity. He consumes
water as required throughout the fast. The concentration of glucose in his blood 2 hours
after his last meal is 4.8mmol/L and after 40 hours of fasting, it is 4.9 mmol/L.
(a) Why is it important that circulating glucose is maintained near constant during
(3 minutes)
(b) For each of the following tissues, discuss the metabolic processes that are relevant
to maintenance of blood glucose at 40 hours of fasting.
(i) skeletal muscle
(ii) adipose tissue
(iii) liver
[The use of diagrams is encouraged. An overview of relevant biochemical pathways
should be included but details of individual steps in pathways are not required].
(17 minutes)


2001 - Question 4.
Ron Elliot, a well-trained middle-distance athlete, is competing in his club 1500m championship.
As expected his respiratory minute volume increases during the initial stages of the race,
providing extra oxygen to support the increased activity.
(a) Discuss the changes occurring during the race in the region of the active skeletal muscles
that contribute to the increased delivery of oxygen to the muscle fibres. Identify any
controls promoting these changes. In your answer, include effects on blood flow and on
[12 minutes]
(b) For much of the race, the increases in oxygen delivery to the muscles ensure that oxidative
phosphorylation is the major contributor to their energy generation. Describe the
production of energy by oxidative phosphorylation and indicate the role played by oxygen
in this process.
[13 minutes]
(c) Ron is narrowly beaten in a final sprint to the finish line with several other runners.
During this sprint, Ron experiences substantial pain in his leg muscles. He attributes this
to an accumulation of lactate in the tissue. Explain why lactate accumulates during the
final part of the race and indicate the significance of this change for energy production.
[8 minutes]


2002 - Question 5
Following ingestion of a typical meal containing carbohydrates, lipids and proteins the concentrations
of glucose and amino acids in the blood rise but then fall back to fasting levels after 2-3 hours.
(a) Discuss the cellular processes that help to limit the increases in circulating glucose. In your
answer, outline the metabolic fates of the glucose, identify the main tissues involved and briefly
discuss the major molecular controls that promote glucose use within the first hour following a
(15 minutes)
(b) During the period when amino acid concentrations in blood are high, there is found to be
increased nitrogen excretion in urine. Outline the metabolic processes leading to this increased N~
excretion, mentioning the main tissue(s) involved.
(5 minutes)
(c) Would you expect ketone body production within the first hour after the meal? Briefly explain
your answer.
(5 minutes)


2003 - Matthew Oldfield is a 12-month old infant, brought to a paediatric clinic after being referred by the local Child Health Service. Matt's height and weight are in the tenth percentile (lowest 10%) for his age, although his abdomen appears somewhat enlarged. His mother is concerned that Mart seems weaker and less active than his older sister at a similar age. She says that Matt often appears pale and sweaty. “He seemed okay when I was breast feeding him regularly. but since he was weaned he often seems listless and droopy".
5. Summarise the key information about Matt and suggest two hypotheses that you think could best explain his problems. Give a brief rationale for each hypothesis, explaining how your hypothesis relates to the key information.
[15 min]
6. List three (3) pieces of information you would want with highest priority from history, physical examination or other investigation to help differentiate between your hypotheses and understand the cause(s) of Matt's problem. Explain your reasoning.
[10 min ]

His mother says Matt has a good appetite and consumes a reasonably balanced diet. She believes that Matt’s episodes of appearing pale, sweaty and “generally lacking energy” are worst before breakfast and improve after meals. Matt has not had other major health problems.
Physical Examination and Laboratory Fidigs
Temperature 37°6C, lungs clear, heart sounds normal. The abdomen is distended. Palpation reveals a greatly enlarged. firm smooth liver. Laboratory findings for a fasting blood sample included the following:

Glucose 2.8 mmol/L (3.5 - 5.0)
Free fatty acid 1.5 mmol/L (0.3 - 0.8)
Measurements of plasma glucagon concentrations established that the fasting level was about twice normal.
Glucagon levels were also measured after an oral glucose load and were found to be normal.
7. (a) Outline the metabolic processes (utilisation and production) that normally affect glucose concentration in the blood during an ovemight fast. Indicate the tissue(s) involved in these processes.
(b) Is there evidence that any of these processes are abnormal in Matt? Explain.
[17 min]
8. (a) In what ways does glucagon influence the processes affecting blood glucose concentration (as outlined in Question 8a). Outline how glucagon controls the key regulatory enzymes. (It is not necessary to give full details of glucagon signal transduction - an overview of these steps will be adequate).
(h) Is there evidence of defective glucagon secretion in Matt? Explain.
[8 min]
9. Suggest one reason for high free fatty acid levels found in Matt’s blood.
[3 min]
10. What is now your favoured hypothesis for the cause of Matt’s problems? Explain your reasoning.
[7 min]

Further Investigation
A liver biopsy was taken from Matt Oldfield. Abnormally enlarged hepatocytes were found to contain excessive amounts of glycogen. Activities of enzymes of carbohydrate metabolism were found to be normal. with the exception of the activity of glucose-6~phosphatase (which catalyses the conversion of glucose-6-phosphate to glucose). which was less than 10% of the normal value.
11. Given this information. briefly summarise why Matt appears to be most lacking in energy before breakfast? (This may require you to repeat some points from previous answers).
[4 min]
Additional Investigation
Further measurements on a blood sample from Matt revealed a lactate concentration of 6.2 mmol/L (normal <2.0), which was interpreted as resulting from impaired lactate utilisation. Arterial “blood gas” measurements were performed:
pH 7.25 (7.35 - 7.44)
PCO; 28 mmHg (35 - 45)
HCO3_ 12 mmol/L (21 - 35)
12. Discuss the response in Matt’ s body to the elevation of lactic acid concentration in his blood. Account for the findings in the arterial blood sample, referring in particular to the nature of, and mechanisms controlling, any respiratory response.
[ 10 min]
13. In thinking about treatment for Matt. discuss a desirable dietary regime. In particular:
(a) How would you suggest managing his carbohydrate intake?
(b) Would increasing the proportion of protein in his diet be desirable to improve his slow growth?
Explain your answers.
[6 min]


2004 - Question 5.
Measurements on middle distance athletes before and after a race establish that muscle glycogen stores are partly depleted during the race.
a) Outline hormonal and intracellular mechanisms that lead to breakdown of muscle glycogen during exercise.
(10 marks)
b) Indicate how glycogen breakdown is likely to contribute to performance when sprinting at the end of a 1500m race.
(4 marks)


2004 - Question 6.
In a normal person, the blood glucose concentration after five days without food is similar to that following an overnight fast.
a) Why is this preservation of blood glucose concentration important for normal function?
(3 marks)
b) (i) What are the major precursors for glucose generation after five days without food?
(ii) Discuss the molecular events and cellular controls operating to ensure an adequate supply of these precursors
(9 marks)
c) (i) What change would you expect in the concentration of acetoacetate (a ketone body) after five days without food?
(ii) Outline the molecular events resulting in this change. (You should include an outline of the relevant metabolic pathways but not details of individual reactions.)
(iii) What is the biological significance of this response in prolonged fasting?
(8 marks)


2004 - Question 7.
The following "blood gas" measurements were obtained from an arterial blood sample. These indicate that the patient is acidotic.
Reference Range
pH 7.38 (7.35 - 7.45)
PCO2 26 (35 - 45)
HCO3 12 (21 - 32)
a) Is this a "metabolic" or "respiratory" acidosis? Explain your answer.
(5 marks)
b) Suggest three conditions that could produce such a profile on "blood gas" analysis. Briefly explain your choices.
(5 marks)
Question 4.
Ingestion of a typical meal consisting of a mixture of carbohydrates, proteins and lipids results in a moderate increase in blood glucose. The glucose concentration then returns to fasting values within the following two hours.
a) Describe the processes leading to rapid removal of glucose from the circulation following a meal. Discuss the major fates of this glucose in liver and muscle. (You should outline any relevant metabolic pathways but do not need to provide details of most of the intermediate metabolites or enzymes.)
(11 marks)
b) Amino acids typically show larger increases in concentration in the blood than glucose following a meal but also return to fasting values within the first two to three hours. Discuss the main fates of the circulating amino acids at this time and identify the major tissues involved. (Again, you should outline relevant metabolic pathways but do not need to provide details of most intermediate metabolites or enzymes.)
(9 marks)
c) Discuss the main hormonal changes that influence glucose and amino acid metabolism in response to feeding. Identify the source of these hormones and factors affecting their release. (You do not need to discuss the cellular effects of these hormones.)
(6 marks)
d) The hormonal response to a meal that is rich in protein but contains little carbohydrate is different to that produced by a more balanced meal. Describe the hormonal response to a protein-rich meal and briefly discuss how this helps to produce an appropriate metabolic response in the body.
(4 marks)


Azam Habib is a 17 year old who recently completed high school and has been working for about 2 weeks in an insurance office. His co-workers have found him to be a thin, earnest young man, keen to be accepted by the group of clerks around his age in the office. When two colleagues arrive early for work, Azam is already at his desk. They invite him to join them for a quick breakfast and are surprised when he responds, somewhat irritably: “I am hungry but I have to get these estimates done and I’m having enough trouble concentrating with this headache, without you clowns distracting me”. When the friends suggest he must have had a bad night, Azam says he was at the gym and sauna trying to make the lightweight limit for his boxing club. “The weigh-in is later today”, he says. When the two colleagues return from breakfast, they find Azam looking pale and drowsy. When they ask if he is okay, they get a rather confused response. They decide they need to take him to an Emergency Department a couple of blocks from their office.
Question 7.
List key information about Azam and his problem. Then outline 2 hypotheses you consider most likely to account for Azam’s condition. For each hypothesis, briefly explain how the hypothesis relates to Azam’s problems (ie suggest mechanisms).
(12 marks)
Question 8.
Assume that Azam is not sufficiently coherent to answer questions; and that the Emergency Department to which he is taken has typical hospital resources for diagnostic testing. What physical signs would you look for and which initial investigations would be relevant? Indicate how possible findings would help confirm, eliminate, or differentiate between your hypotheses.
(8 marks)
Azam is given oral glucose and responds quickly, becoming more alert and coherent. The medical officer asks him about his Type 1 diabetes and Azam says that he was diagnosed when he was 13. “But I injected my insulin this morning like always” he says. He tells the doctor that he is only just under the boxing lightweight limit and that he skipped breakfast and planned to eat after the weigh-in at his boxing club later in the day. He has not eaten since the previous evening when he had a drink and some fruit after a work-out at the gym and brief stop in the sauna.
Question 10.
It is now at least 12 hours since Azam’s last food intake.
(a) For a normal person, 12 hours after their last meal, outline the metabolic processes that help to maintain blood glucose concentrations in the 3.0 – 5.5 mmol/L range. In your answer, identify key tissues involved and any precursors that are important for glucose production. (It is not necessary to give details of all intermediate metabolites in the pathways you describe.)
(14 marks)
(b) How would Azam’s injection of insulin that morning after an overnight fast influence the concentration of glucose in his blood. Outline key controls on the relevant pathways and how insulin affects these controls. (It is not necessary to give details of insulin signal transduction.)
(10 marks)
(c) Would you expect ketone body concentrations to be elevated in Azam’s blood? Explain.
(3 marks)
(d) How would Azam’s urea production compare with that of a normal person after 12 hours of fasting?
(3 marks)


2007 - Question 5.
Peter Randall visits his GP because he has gained about 10 kg in weight over the last two years and is
worried about the possible implications for his future health. Peter is a 44-year-old male who works for a
local law firm. He walks to and from work each day (about 20 min each way) but does little other regular
physical activity. Discussion about his diet indicates that his food intake is not unusually high. However, he
consumes substantial amounts of sugary soft drinks as his main source of fluids both during and between
(a) What are likely to be the main uses of energy for Peter?
(4 marks)
(b) Peter’s most recent meal after an overnight fast, was a late breakfast consisting of a Danish pastry
and 500 ml of a “full-sugar” soft drink, eaten at 10:00 am. Assume that Peter does not have a
metabolic disorder, such as diabetes mellitus.
(i) Show graphically, the likely changes in his blood glucose over the 3 hours from 10:00 am to
1:00 pm (including approximate values for the concentration of glucose in his blood)
(3 marks)
(ii) Describe the cellular and molecular processes for converting glucose to stored fat. Mention
the tissue(s) involved, how glucose enters the relevant cells, key intermediates in the
pathways and the main controls that promote conversion of glucose to fat.
(14 marks)


(c) Some excess glucose is also stored as glycogen.
(i) Where is glycogen stored and what role(s) does it play?
(4 marks)
(ii) Identify two advantages and two disadvantages of storing excess glucose as fat rather than as
(4 marks)