SAQs:

Name two types of drugs used to treat Influenza infection and the targets they act upon. (2)
1. Inhibition of M2 Channel
● Low pH inside the endosome activates the M2 channel on virus capsid
● Allows protons to move into the virus and undo the bonds holding the capsid
together
● Conformational HA change for fusion with endosome
● This allows uncoating of the virus and the release of its contents into the host cell
cytoplasm
● Translation, genome replication, assembly etc
● If M2 is blocked, the virus will remain locked in its own shell and won’t gain access
to the host cell's genetic machinery
● ADAMANTANES: amantadine and rimantadine

2. Neuraminidase (NA)
● Neuraminidase is produced by influenza virus
● Virus enters the cell: HA binds to sialic acid (SA)
● During infection and replication, the host cell gradually dies
● New viruses leave the cell and want to move onto new healthier cells
● So, virus produces neuraminidase which moves to the cell surface and destroys sialic
acid so the original cell is less likely to get infected by the daughter viruses
● IF WE INHIBIT NEURAMINIDASE - the enzymes will latch back down to the old cell
and will not spread so the infection will be contained within the patient
● The structure of neuraminidase is well known allowing the design of a substrate
analogue which avidly sits in the neuraminidase binding pocket and acts as an
inhibitor
● Neuraminidase Inhibitors:
○ Zanamivir (Relenza)
○ Oseltamivir (Tamiflu)

List 4 factors that led to the eradication of small pox. (4)

•No animal reservoir
•No latent or persistent infection
•Easily recognised disease
•No resistant strains to vaccine

List 4 stages of the HIV life cycle that can be inhibited by current anti-viral drugs. (2?)
● NRTI (Nucleoside Reverse Transcriptase Inhibitor)
○ Zidovudine
○ Stavudine
● NNRTI (Non-Nucleoside Reverse Transcriptase Inhibitor)
 Binds enzymes but not at the active site
○ Efavirenz
○ Viramune
● Integrase Inhibitor
○ Raltegravir
● Entry Inhibitors
○ Maraviroc - blocks gp120 - CXCR4 interaction
○ Enfuvirtide - binds gp41 - prevents membrane fusion
● Protease Inhibitors
○ Atazanavir (taken with Ritonavir)

Briefly describe why a combination of anti-viral drugs are used against HIV. (2)

The reverse transcriptase of a virus is so error prone that virus resistance to a single drug
emerges rapidly (since no proofreading mechanism available). Combination is more effective.

Diagram of DNA strand with exons labelled. Mark the introns. (1)

Start – GU End - AG

Define an intron and an exon, explaining their relationship with mRNA and the translated
product. (3).

Introns are DNA that is transcribed to mRNA but not expressed in the final protein
product, instead removed before translation.

An exon is a part of the gene that codes for a protein and is expressed in the final
product. Exons spliced together to make mRNA.

What is the name of the DNA strand that is used as a template? (1)

Sense/coding strand

What do you call the part of the gene where transcription is initiated? (1)

Gene promoter

How does TFIID help with transcription? (2)

TF IID consists of TATA Binding Protein (TBP) and TBP Accessory Factors (TAFs). When they bind
to TATA:
● Partially unwinds the DNA and widens minor groove thus allowing extensive contact
with bases.
● Unwinding is asymmetrical with respect to TBP-TATA complex thus assuring
transcription Is unidirectional.
Name two post-transcriptional modifications made to the mRNA transcript and indicate where
they are placed. (2)

A 7-methylguanlate cap is added to the 5’ end. Cap is formed by hydrolysis of

terminal mRNA triphosphate to diphosphate, then methylation at N7 position on
purine ring. The cap protects mRNA and enhances translation. Polio virus is able to
interfere with this cap.

A Poly A tail is added (polyadenylation) about 20 bases downstream of the sequence

AAUAAA on the 3’ end of the mRNA. Only eukaryotes have Poly A tail, not in
bacteria.

Diagram of a haplotype (I think). Asked to identify. (2)

● MHC Haplotype - group of MHC alleles linked together on a single chromosome
● We have two MHC haplotypes because we are diploid

Give four structural differences between the B cell and T cell receptors. (4)

● The BCR is a transmembrane protein complex consisting of a membrane-anchored

antibody and di-sulphite linked heterodimers Iga and Igb
● Iga/Igb have an immunoglobulin like fold
● The cytoplasmic tails of the mIg (membrane-bound Ig) is too short to signal
● The cytoplasmic tails of Iga/Igb is long enough to interact with intracellular signalling
molecules
● When the BCR recognises an antigen, there is a structural change which drives
signalling via Iga/Igb
T cell receptor:

● A small subset uses gamma and delta chains

● Alpha and Beta chains of the TCR have SHORT CYTOPLASMIC TAILS
● There are charged residues in the transmembrane region of the alpha and beta chains
that interact with oppositely charged residues in the transmembrane region of CD3
polypeptides
Diagram of MHCI. Identify the molecule and give its function. (2)

The CD8 co-receptor on lymphocytes binds to the relevant CD8 regions on the side of
the MHC molecule

T cells have CD4 and CD8 receptors. Give two functions of these receptors. (2)

MHC Class I presents peptides derived from endogenous antigens to CD8+ T cells.
MHC Class II presents peptides derived from exogenous antigens to CD4+ T cells. CD4
and CD8 are co-receptors; bind to side of MHC molecule. TCR binds directly. These co-
receptors bind to the relevant MHC and increase the avidity of T cell-target cell
interaction and are important in signalling.
● CD4 - T helper cells
○ Secretes cytokines
○ Recruit effector cells - activate macrophages
○ Help and activate CTL and B cell responses
● CD8 - Cytotoxic T Lymphocytes
○ Kill target cells
○ Induce apoptosis in target cells

Diagram of CCR5. Name the secondary structural features of the protein. (3)
General features of secondary structures: Hydrogen bonds between the C=O of one residue
and the N-H of another residue.

Beta-pleated sheets are stabilised by hydrogen bonds

● Hydrogen bonds between the C=O and the N-H of two or more beta strands hold the
entire structure together
Alpha helices
● The side chains of individual amino acids project out from within the alpha helix
● In theory, helices can be right handed or left handed
● The usage of L-amino acids in proteins means that right handed helices are favoured
In the portion of the protein indicated there are amino acids with hydrophobic side chains.
Describe the interactions that would occur between these side chains. (3)
● Hydrophobic side chains close together by packing them into the interior of the protein.
This creates a hydrophobic core and a hydrophilic surface to the majority of proteins

NADH dehydrogenase complex is another example of a membrane protein in the inner

mitochondrial membrane. Describe its roles in ATP synthesis briefly describing the four steps
from NADH to ATP. (4)
Membrane Complexes:
1. NADH Dehydrogenase Complex
2. Cytochrome b-c1 Complex
3. Cytochrome Oxidase Complex

Mobile Carriers
1. Co-enzyme Q (ubiquinone)
2. Cytochrome C

The proteins accept electrons and in doing so, a proton from the aqueous solution. Each
successive membrane complex or carrier has a more positive redox potential than the previous
component of the ETC. This means that the transfer of electrons from one complex to the next is
energetically favourable. As they progress along the chain, the electrons lose energy. When
electrons pass through each complex, protons are pumped to the intermembrane space.

Ubiquinone (co-enzyme Q) is an electron carrier which transfers electron from NADH

Dehydrogenase Complex to Cytochrome b-c1.
It can pick up one or two electrons (together with an H+ from solution). Cytochrome Oxidase
initially receives 2 electrons from cytochrome C in the first cycle then the cycle repeats so that
cytochrome oxidase has 4 electrons in total.
Cytochrome oxidase passes the electrons to Oxygen to generate water.
Furthermore, 4 protons are pumped into the intermembrane space, thus enhancing the proton
gradient. Oxygen is the ideal terminal electron acceptor because it has a high affinity for
electrons.

ATP Synthase is a multimeric enzyme consisting of a membrane bound part (F0) and a part
which projects into the matrix space (F1).
F1 and F0 consist of three different subunits:
F0 = a, b and c
F1 = a, b and g

As the g subunit functions as an asymmetrical axle, the b-subunits are compelled to undergo
structural changes. This rotation drives transitions of the catalytic portions of the b-subunits,
which alters their affinities for ATP and ADP. So, TORSIONAL ENERGY flows from the catalytic
subunit into the bound ADP and Pi to promote the formation of ATP.
The coding strand of part of a gene is shown below. EcoRI is a restriction endonuclease that
cleaves DNA at the sequence GAATTC. In a disease, this gene is cleaved by EcoRI but not in the
normal version of the gene. Assuming it is a single nucleotide mutation, mark on the sequence
where the mutation would be. (It was a nucleotide change that affected a serine amino acid)
(There were a few other serines shown to be coded for by the sequence). (1)

Find the sequence that reads GAATTC save for one letter - mark the letter.

When treated with an enzyme that cleaves N-linked carbohydrate there is a loss in molecular
weight of the disease protein product but not the normal protein. Explain this with reference to
the amino acid and codon change (3) and suggest a method for differentiating between the
different molecular weights of protein (1).
GEL ELECTROPHORESIS - proteins migrate through gel pores. Takes into account charge
and size. (electrophoresis - just charge)
Codon change causes different amino acid to be formed. This amino acid is a different
weight to the original amino acid, and thus the protein weight is different.
What does it mean that the disease has 100% penetrance? (1)
Symptoms are always present in an individual with a disease-causing mutation.
Genetic pedigree diagram showing a few affected individuals in each generation, both males and
females. The proband arrow pointed to a black square. Identify the sex of the patient. (1) Male
Identify the mode of inheritance. (1) Dominant? Depends
Name 4 things required for PCR. (2) DNA template, DNA polymerase enzyme, primers,
nucleotides (dNTPs)
A centrifuge was performed. The packed cell length was 3.5 cm and the centrifuge capillary tube
was 10 cm. Calculate the haematocrit and identify the sex of the patient. (2)
3.5/10 *100

Haematocrit = percentage of a sample of blood occupied by RBCs. Once you’ve

centrifuged the blood, cells will be in tight layer at bottom. Ratio of length of red in
tube to length of whole tube = Hct. Times 100 for percentage. Male range = 40-52
(46). Female range = 35-47 (41).

A blood sample is diluted 1000 fold and blood is placed on a haemocytometer with a
volume of 1 x 10-7 litres. 350 cells are counted. Calculate the red blood cell count per
litre. (2)
350 cells in 1/1000 of 1 x 10^-7 litres
1/1000 = 10^-3
So 350 in 1 x 10^-10
350 x 10^10 cells per litre
The haemoglobin concentration of the blood is 140 grams per litre, using values calculated
above, calculate the mean cell haemoglobin concentration. (2)

MCHC = (Hb x 100)/Hct so(140 x 100)/350 x 10^10

Define anaemia. (1) Low blood Hb levels

List the types of anaemia that are associated with cell size. (3)
MICROCYTIC (small MCV)
Caused by menstruation, GIT lesions or cancer
NORMOCYTIC (normal MCV)
Caused by acute blood loss
MACROCYTIC (high MCV)
DNA synthesis and cell division fail and there is reduced cell division of progenitor cells so you
get LARGE erythrocytes.
Caused by vitamin B12 deficiency (pernicious anaemia)

Define oedema and give 4 underlying causes (5)

Oedema is an abnormal increase in interstitial fluid due, causing swelling of tissues.
Increased blood pressure due to:
Left ventricular failure (causes raised hydrostatic pressure)
Nephrotic syndrome/kidney failure (blood pressure isn’t regulated)
Endothelial wall damage/inflammation (increased permeability of fluid form
capillaries to tissues
Hepatic failure (to do with decrease in plasma proteins, disrupts osmoregularity)
Decreased lymphatic drainage

Define infarction (1) and give 2 mechanisms that can lead to infarction (1/2 mark each).

Cell or tissue necrosis (death) due to unresolved ischaemia (impaired supply of

oxygenated blood to tissues). Caused by obstruction of an artery or vein (maybe via
thromboembolism).

A woman calls her doctor due to pain in her calf following colon surgery. She dies suddenly.
Identify the cause of death and explain the major events that led up to her death. (3)

Following surgery, she suffered a deep vein thrombosis. A part of the clot then broke
off and travelled in her circulatory system to her pulmonary arteries where it then
prevented her venous return from being oxygenated. This caused her to suffer from a
pulmonary thromboembolism, this lead to anoxia and subsequently death