POM EQs

Question 1

How many phosphoanhydride bonds are broken during the oxidation of palmitic acid and at which stage? (1 mark)

Answer 1

2 phosphpanhydride bonds. (0.5 mark)

In the intial step of beta oxidation, when converting a fatty acid into an acyl CoA. This breaks down ATP to AMP. (0.5 mark)

Question 2

Why does fat metabolism have to be balanced with carbohydrate metabolism? (2 marks)

Answer 2

Acetyl CoA from beta oxidation (0.5 mark) can only enter the TCA cycle if oxaloacetate is present (0.5 mark).

Oxaloacetate is formed from pyruvate (0.5 mark), which in turn is formed from carbohydrate metabolism (0.5 mark).

Question 3

A child went to sleep at 10pm having not eaten since 5pm. He frequently experiences appetite loss and vomiting. However, on this occasion, he was found in a coma the next morning by his parents. When the paramedics arrived they gave him i.v. glucose, after which he made a full recovery. He is not diabetic. What condition is this child likely to have and how did it result in a coma? (3 marks)

Answer 3

MCADD (0.5 mark) |OR| medium-chain acyl CoA Dehydrogenase Deficiency (1 mark)

MCAD is used during the beta-oxidation reaction of medium chain fatty acids (0.5 mark).

Lack of MCAD means that fatty acids cannot be efficiently oxidised (0.5 mark).

Since the child has undergone prolonged fasting (0.5 mark) he is reliant upon lipolysis and beta-oxidation which struggles to meet the energy demands of the brain (0.5 mark).

Question 4

Explain how MCADD can be managed?

Answer 4

Carbohydrate rich diet

Question 5

Antonio is on medication for a long-standing diagnosis of Crohn’s disease, which may involve ulcers of the small intestine. He subsequently develops iron-deficiency anaemia. What is the most likely cause of the anaemia?

Answer 5

Gastrointestinal blood loss. Intestinal bleeding is a key feature of Crohn’s disease due to ulceration of the gut. The amount of blood loss can lead to iron-deficiency anaemia due to the decrease in haemoglobin concentration of the blood.

Question 6

Patients suffering Crohn’s disease usually have ulcerations that can lead to internal bleeding which led to the development of iron-deficiency anaemia. What are the 3 further symptoms patients may attain?

Answer 6

Fatigue, breathlessness upon exertion, and weakness

Question 7

Henry has heard about blood donation from a friend at work but is worried that he will not be eligible for this. List 4 reasons as to why he may not be able to donate blood. (4 marks)

Answer 7

Any 4 of the following:
Tattoo from unlicensed parlour
Blood borne infections e.g. (HIV)
Low BMI
Recent infection
Takes injectable drugs
Recent piercing
On antibiotics

Question 8

Henry has severe haemophilia B. As part of his treatment, he receives regular infusions to help him live a normal life. What is meant by ‘severe’ haemophilia? what kind of infusion does he receive, and why does it help his condition? (3 marks)

Answer 8

Severe’ haemophilia refers to undetectable plasma levels of factor IX (haemophilia B) or factor VIII (haemophilia A) (1 mark). Henry receives infusions of recombinant factor IX concentrate (1 mark). These are known as prophylaxis, and reduce the risk of spontaneous bleeding, which he would be prone to given the severity of his disease (1 mark).

Question 9

Sonia has beta-thalassemia major. Explain how the disease is acquired, which molecules are involved, the type of anaemia that Sonia may have as a result, and the management options available for her disease. (3 marks)

Answer 9

Beta-thalassemia is a blood disorder inherited in an autosomal recessive fashion (0.5 mark) affecting the beta chains of haemoglobin (0.5 mark). Sonia would have a, microcytic anaemia as a result of this disease (1 mark) (due to failure to produce haemoglobin effectively). Blood transfusions may be given to treat the anaemia (1 mark) (with chelation therapy to prevent iron overload).

Question 10

Matupo suffers from HbSS (sickle cell anaemia) and experiences a lot of pain in his feet following exercise. This is due to a vaso-occlusive crisis. What explains the mechanism for Matupo’s vaso-occlusive crisis?
A) Polymerisation of de-oxygenated haemoglobin
B) Thrombocytosis as a result of SCD
C) Abnormally excessive vasoconstriction
D) Burst berry aneurysm
E) Impaired fibrinolysis

Answer 10

Option A. Deoxygenated HbS results in sickle-shaped erythrocytes due to polymerisation. These cells may get lodged in small blood vessels, leading to vaso-occlusion and subsequent pain.

Question 11

How is thrombocytosis develops in patient with sickle cell disease?

Answer 11

Thrombocytosis is commonly seen in patients with sickle cell disease as a result of increased bone marrow activity and functional hyposplenisim.

Question 12

Alport Syndrome is an X-linked condition that may be inherited in a dominant or recessive form. This syndrome affects collagen IV, leading to loss of kidney function, hearing loss and eye abnormalities. However, even after inheriting the dominant form, some females may remain unaffected. How is this possible?

Answer 12

One of the X chromosomes in females is condensed into heterochromatin. This is called X-inactivation making one of the X chromosomes inactive. This is a form of dosage compensation to ensuring that number of genes in males and females are equal.

Question 13

As part of a lab experiment, Harry uses a haemocytometer to study a sample of blood. What kind of measurement could he get from using a haemocytometer?

Answer 13

Cell count is measured by using a haemocytometer where the number of cells in the region of the grid are counted. This number can be scaled up for the desired volume of the sample.

Question 14

What is used to measure haemoglobin concentration and haematocrit?

Answer 14

Heamoglobin concentration is usually measured using visible absorption spectroscopy.

Heamatocrit is measured using centrifugation of a blood sample to separate the plasma from the red cells.

Question 15

What is erythrocyte sedimentation rate (ESR)?

Answer 15

ESR describes how long it takes for RBC to settle at bottom of the tube.

Question 16

Gregory is looking to study a blood sample under a microscope. To do this, he uses Leishman’s stain to prepare the slide. He notices that upon applying the dye to the sample, some cells appear pink whilst others appear dark purple. Which of the following is an explanation for this?

Answer 16

The nuclei of WBCs retain the blue/purple dye. RBCs don’t have nuclei which means that they do not retain the blue dye but cytoplasm causes it to show up pink. Remainder: Leishman’s stain contains a purple dye, which is retained by the organelles of white blood cells, and a pink dye which the cytoplasm of the red blood cells retains.

Question 17

Describe how an E-test works (2 marks). Hint: diagnosis of infection topic

Answer 17

An agar plate is inoculated with bacteria (0.5 marks).

A test strip containing antibiotic is placed on the agar plate (0.5 marks).

An area where bacteria do not grow will form around the strip, due to the presence of the antibiotic (0.5 marks).

Measure the areas greatest length using the labelled test strip and note its value where the eclipse clear zone intersects the strip, which is the MIC (μg/mL) (0.5 marks).

Question 18

A patient is diagnosed with streptococcal pneumonia and is treated with penicillin. After initial success, despite adhering to recommended dosage, his symptoms worsened again. Explain the change in MIC. (1 mark)

Answer 18

Bacteria have become resistant to the antibiotic (0.5 marks) causing a rise in MIC (0.5 marks).

Question 19

Describe a method of testing for antibiotic resistance in bacteria , other than the E-test. (2 marks)

Answer 19

Agar plates are spread with a lawn of bacteria and disks containing defined concentrations of antibiotic are added (1 mark). After incubation the zone of inhibition around the disk is measures to determine sensitivity of resistance (1 mark).

Question 20

Two obese males (A and B) of similar age begin treatment with orlistat. They have their low-density lipoprotein (LDL) levels measured for two years following the start of this weight-loss treatment. Results in the grown show that person A has a greater decrease of LDL than person B.

Which statement would best explain the differences between person A and person B?

Note: a decrease in LDL levels is a direct consequence of decreased cholesterol.

A: Person B is undertaking regular exercising and person A is not
B: Person B has type II diabetes and person B does not
C: Person B is less obese than person A
D: Person A is taking a statin and person B is not
E: Person B has a diet lower in salt and saturated fats

Answer 20

Option D. This is because statins inhibit HMG-CoA reductase, involved in the rate -determining step of cholesterol synthesis. This would lead to lower cholesterol production.

Question 21

The pyruvate dehydrogenase complex (PDC) generates acetyl CoA from pyruvate, thereby linking glycolysis and the TCA cycle. The condition known as Beriberi is caused by impairment of this reaction. What is the underlying disease mechanism? What are the symptoms of this disease?

Answer 21

Beriberi disease is caused by deficiency of thiamine (vitamin B1). This leads to a deficiency in the derivative thymine pyrophosphate (TPP).

TPP is a key component of PDH complex as it is prosthetic group forming the PDH complex.

Less TPP results in less ATP production resulting in symptoms such as peripheral nervous system damage, muscle weakness and decreased cardiac output.

Question 22

Sulphonylureas are a treatment commonly used for Type 2 Diabetes Mellitus patients. They stimulate insulin release. A study investigating sulphonylurea efficacy showed that in some patients sulfonylureas are less effective. Common confounding factors were accounted for. What could be the cause of this reduced sensitivity?

A: The dosage was too high causing resistance to develop
B: Insulin treatment interacting with the sulphonylurea reducing its efficacy
C: Gene polymorphisms leading to altered target proteins
D: Poor patient compliance leading to resistant target proteins developing
E: Overweight patients tend to have reduced sensitivity

Answer 22

Option C. Variations in genes can lead to reduced drug efficacy in some patients

Question 23

What is pharmacogenetics? What are the two therapeutic uses of pharmacogenetics?

Answer 23

Pharmacogenetics is the study of how the genetic variation of each individual can affect their response to drugs

Pharmacogenetics can be used to:
Prevent Serious Adverse Drug Responses (SADR), which is a significant reaction to administered drugs. This can be done by testing for certain alleles that usually lead to SADR

Select targets for drugs such as certain cell receptors
This can be done by studying polymorphisms associated with a disease to determine if a person has a target site for a drugs

Question 24

A 35-year-old male is infertile and has decreased testicular function. Using his karyotype determine the cause of his clinical presentation.

The karyotype shows that the male has two X chromosomes.

A: Hypermethylation of the SRY gene
B: Downs syndrome
C: Y chromosome microdeletion
D: Micro-duplication causing low sperm motility
E: SRY translocation

Answer 24

Option E. There is no Y chromosome in the karyotype but rather two X chromosomes. However, the patient is biologically a male meaning that SRY translocation is likely to have occurred (although the translocation cannot be seen on the karyogram). SRY translocation can cause infertility and reduced testicular function.

Question 25

A 40-year-old female is expecting her first child. Although she has no genetic conditions in her family, the doctor recommends testing for Down’s syndrome. Why has the doctor recommended this?

Answer 25

Increasing maternal age means eggs are halted in prophase of meiosis for a longer time which increases the risk of genetic abnormalities.

Question 26

What mechanism prevents the T-cell from being auto-reactive before entering circulation? (3 marks)

Answer 26

Auto-reactive T-cells are suppressed/prevented from entering circulation in the thymus (1 mark). This is mediated by AIRE (a transcription factor) (1 mark). The AIRE transcription factor is responsible for expressing peripheral antigens in the thymus to prevent the development of auto-reactive T cells (1 mark).

Question 27

Name four mechanisms involved in regulation of the T-cell response after entering circulation and explain how each of these prevent autoimmunity. (4marks)

Answer 27

Regulation – T regulatory cells produce IL-10 cytokines which downregulates other self-reactive T cells. This regulation is done by the FoxP3 transcription factor (needed for Treg development) (1 mark)

Anergy – The naïve T cells need co-stimulatory signals to become activated. If the antigens presented (on self-cells) do not give co-stimulatory signals, then the T cell will be apoptosed. (1 mark)

 Ignorance – Antigen may be present in too low a concentration to reach the threshold for T cell receptor triggering. (1 mark)

Deletion – T cells that bind to self-cells die in circulation due to Fas-Fas linkages. Here, T cells are activated to be killed. (1 mark)

Question 28

IPEX (Immuno-dysregulation Polyendocrinopathy Enteropathy X-linked syndrome) is a rare disease where there is a mutation in the FoxP3 transcription factor. Explain how having this mutation would affect an individual. (3 marks)

Answer 28

The FoxP3 transcription factor is needed for the development of Treg cells (1 mark) and Treg cells are needed for regulation of peripheral tolerance (1 mark). Peripheral tolerance is weakened/ defective, meaning autoimmune disease to progress (1 mark).

Question 29

Aspirin is a drug that irreversibly inhibits platelets, but only temporarily inhibits endothelial cells from producing prostanoids (such as prostaglandins). What could be a possible explanation for this?

Answer 29

Platelets are unable to generate new RNA for the synthesis of COX unlike endothelial cells. This is because platelets don’t have a nucleus but endothelial cells do.

Question 30

How can arachidonic acid is used to make both thromboxane A2 and prostacyclin PGI2?

Answer 30

Arachidonic acid is converted to prostaglandin by cyclo-oxygenase.

Prostaglandin is converted to prostacyclin PGI2 and Thromboxane A2 by prostacyclin and thromboxane synthase respectively.

Question 31

A pharmaceutical company is considering developing a drug that inhibits the TP-α receptor. What effect might this have?

A: Binds circulating prothrombin to prevent clot formation

B: Causes increased localised vasoconstriction in small vessels

C: Reduces the production of COX enzymes by endothelial cells

D: Activates tissue plasminogen activator (tPA) to reduce coagulability

E: Causes a significant reduction in platelet activation

Answer 31

Option E. The TP-α receptor is located on platelets and causes platelet aggregation and adhesion upon activation. This shows that thromboxane A2 act in an autocrine manner.

Question 32

How is the binding of thrombin to thrombomodulin led to inactivation of factor Va and VIIIa?

Answer 32

Thrombomodulin binds to thrombin, which catalyses protein C activation. The activated protein C then forms an enzyme complex with protein S. This complex inactivates Factor Va and Factor VIIIa.

Question 33

What is Fluorescence In-Situ Hybridisation? What do they usefully identify ?

Answer 33

Fluorescence In-Situ Hybridisation is a technique using fluorescent probes to detect the presence of specific gene sequences. The probes are complementary to the relevant sequences, emitting fluorescent light as they bind.

This is useful to identify the presence of gene fusion products. Two different coloured probes are used (e.g. blue and yellow). If a gene fusion product is present, a third colour will be emitted, formed by the combination of the two other probes, i.e. green.

Question 34

Cystic fibrosis is an autosomal recessive condition caused by a mutation in the CFTR gene.

The diagram of a chromosome below indicates with an arrow where the mutation on chromosome 7 is; it is on a light band. The CFTR gene is usually in a dark band. Why do we know that the mutation for this disease is found in a light band? (1 mark)

Answer 34

Light bands contain about 80% of all active genes – i.e. they are the active regions of the chromosome. Chromatin is less condensed (euchromatin) than in the dark regions. Dark bands are more condensed chromatin (heterochromatin) and contain few transcribed genes – i.e. inactive regions of the chromosome.

Therefore, we know that the gene belongs to a light band because the mutation affects the phenotype, meaning that it is being transcribed. (1 mark)

Question 35

Some people have a mutation on the CFTR gene, but they do not have cystic fibrosis; they have a condition known as Congenital Absence of the Vas Deferens (CAVD). What is this phenomenon known as and how does it occur? (2 marks)

Answer 35

Pleiotropy (where one gene can influence multiple apparently unrelated phenotypic traits) (1 mark). They have a different mutation in the same gene (CFTR gene) causing different symptoms (1 mark).

Question 36

Although both had cystic fibrosis, Mrs Leigh’s uncle and Mr Leigh’s aunt had very different symptoms: Mrs Leigh’s uncle suffered from repeat chest infections, while Mr Leigh’s aunt did not. Mr and Mrs Leigh are worried that there might be another genetic disease in their family. Assuming that there is no other genetic disease, what could be the explanation for this difference in symptoms? (1 mark)

Answer 36

The difference in symptoms could be explained by gene interactions.

The two individuals have different genomes. A specific gene variant could be interacting with the CFTR mutation, causing increased susceptibility chest infections in Mrs Leigh’s uncle. (1 mark)

Question 37

a) Ivacaftor is a drug called a CFTR modulator. It corrects the malfunctioning protein in patients with the G551D gating mutation. However, its efficacy varies between different patients. Explain the differences in efficacy. (1 mark)

b) Name a method that could be used to identify which individuals would benefit the most from this treatment. (1 mark)

Answer 37

a) Different mutations cause different protein defects so the drug would only be effective in people with a specific mutation. (1 mark)

b) PCR (1 mark)

Question 38

Chronic myeloid leukaemia (CML) is caused by a translocation between chromosomes 9 and 22. The recombined chromosome called Philadelphia Chromosome. The translocation gives rise to a fusion gene, BCR-ABL1, which produces tyrosine kinase (TK). TK upregulates proliferation pathways within the cells, leading to cancer.

State two techniques that could be used to detect the presence of the tyrosine kinase produced and explain each one? (2 marks)

Answer 38

RT-qPCR – measure amount of transcript of gene fusion product in blood (1 mark)

|AND|

FISH – fluorescently labelled probes for the genes at the breakpoint. Probe for BCR and probe for ABL. Analyse colours to identify fusion (1 mark)

Question 39

Chronic myeloid leukaemia (CML) is caused by a translocation between chromosomes 9 and 22. The recombined chromosome called Philadelphia Chromosome. The translocation gives rise to a fusion gene, BCR-ABL1, which produces tyrosine kinase (TK). TK upregulates proliferation pathways within the cells, leading to cancer.

a) Mrs Wilson has been given Imatinib, a TK inhibitor, for treatment for CML. However, after a.few months, the amount of TK starts to increase again after a decline since the start of the treatment. What has happened and what can be done about it?

b)Explain why part a) happens?

c) Mrs Wilson was planning on having children. Should she worry about her children inheriting this condition? Justify your answer. (2 marks)

Answer 39

a) Cells become resistant to treatment. (1 mark) Alternative treatment. (1 mark)

b)Tumour cells tend to be genetically unstable, i.e. more prone to mutations. (1 mark)

Some of these mutations may confer resistance to a particular treatment (this is why combination therapy is often used). (1 mark)

By giving the treatment, selective pressure is applied. The resistant cells survive and multiply, whilst the others die. This is an application of the theory of natural selection. (1 mark)

c)No because mutation is somatic. Somatic mutations are not inherited.