Tutorials Flashcards
What is acyclovir used to treat
Herpes (cold sores)
Varicella zoster
Immunosuppressed
What is topoisomerase
Enzyme that unravels the DNA in DNA replication
What do kinases and thymidine kinase do
kinase - enzyme that phosphorylates
thymidine kinase - enzyme which makes the protein coat
Explain how selective toxicity is used in acyclovir action
Virus polymerase is different to the host cell polymerase and acyclovir-GTP only works with viral DNA polymerase
Acyclovir is only activated when it contacts thymidine kinase which the virus releases
Which nucleoside does acyclovir have a similar structure to
Deoxyguanosine
Explain how acyclovir is activated
- Acyclovir converted to acyclovir-guanosin monophosphate (Acyclo-GMP) by Thymidine Kinase
- Then Acyclo-GMP is converted into acyclovir-guanosine diphosphate (Acyclo-GDP)
using GUANYLATE KINASE of the host cell. - The Acyclo-GDP is then converted to acyclo-guanosine triphosphate (Acyclo-GTP) by phosphotransferases of the host cell.
Explain how acyclovir works
Acyclovir is incorporated into the viral DNA and because it doesn’t have a 3’ hydroxyl group it can’t continue the chain and join onto another phosphate of a different nucleotide. So the DNA strand terminates and prevents production of viral DNA.
In what tissues is creatine kinase present in high levels
Muscle and the brain use a huge amount of ATP therefore need high levels of CK
Describe the types of CK
made of 2 subunits that are coded for by 2 different genes Present in all cells at low levels Muscle expresses M genes - MM Brain expresses B genes - BB Heart muscle expresses both - BM
Why will CK be found in the blood
Damage to cell membranes allows leakage into the blood
What causes the plasma membrane of myocardial cells to become leaky
Active transport membrane proteins (pumps) stop working because they require ATP to function. High concentrations of everything inside the cells leaks out.
How can CK activity be determined
Coupled assay - use 2 or more reactions to find something detectable
1. Creatine Phosphate + ADP ——–> Creatine + ATP (Creatine Kinase)
2. ATP + D-glucose ——–> ADP + Glucose-6-Phosphate (Hexokinase)
3. Glucose-6-Phosphate + NADP+ ——–> 6-PG + NADPH + H+ (G6P dehydrogenase)
NADPH absorbs UV light
Why will the three isoenzymes of CK be separated by electrophoresis
Similar molecular weight, therefore separation is due to charges
What is a better technique than traditional electrophoresis for separating CK isoenzymes
Isoelectric focussing
Gel with +charge on side and -ve on the other
Isoenzyme moves to three there it has a net charge of zero (isoelectric point)
B - 5.2
M - 6.7
Does an increase in serum CK activity relates to the size or myocardial damage
Levels of BM isoform in the serum are directly proportional to the amount of cell death
What is the time course of serum CK after MI
30 mins to 2.5 days
What markers can be used to diagnose myocardial damage
Lactate dehydrogenase
Troponin
Troponin I and T
Serum glutamate oxaloacetate transaminase
What is anoxaemia and what is the compensatory mechanism
Low oxygen levels in the blood as its used in respiration
Erythropoiesis
Why may skin appear yellow
Subcutaneous fat is depleted
What is the purpose of metabolic coupling of oxidative phosphorylation and ETC
ensures substrates are only metabolised when there is a demand for ATP
Why is the rate of respiration in the presence of succinate and ADP greater than with glutamate plus malate and ADP
Malate feeds into NADH dehydrogenase complex and generates 3 ATP
Succinate feeds via FADH2 and succinate dehydrogenase and generates 2 ATP
To generate the same amount of ATP, more succinate must be oxidised and therefore more oxygen must be used
What occurs when both oligomycin and DNOC are added to mitochondria
DNOC uncouples OP from the ETC and so when oligomycin blocks ATP synthase there is no effect and the ETC runs maximally despite no ATP being produced so the energy is lost as heat
What is the effect of DNOC on the body
Raised temperature due to the ETC
pulmonary ventilation increases as more oxygen is delivered to the respiring cells
Organs fail
Why do those poisoned with DNOC often present rigor mortis
To relax the muscle fibres before the next power stroke, the ADP must be displaced by incoming ATP. DNOC poisoning greatly decreases the concentration of ATP so the contractile system is left contracted.
Why was DNOC discontinued as a weight loss drug
Dosage Issues - the margin between the dose for weight loss and a lethal dose is too narrow to justify its licencing.
What is the typical feature of osteogenesis imperfecta
Repeated fracture of long bones
What is the cause of osteogenesis imperfecta
Point mutation in the gene for type I collagen where thymidine replaces guanosine therefore glucose is substituted with cysteine
cysteine causes a kink in the helix which affects helix formation + sulphide bonding
How can osteogenesis imperfecta be diagnosed
Cross-linked polypeptides of the collagen migrate slowly in electrophoresis in the presence of SDS (depends on size)
2-mercaptoethanol reduces the sulphide bonds so the chains can migrate as normal
Why may two bands appear in electrophoresis for osteogenesis imperfecta
two alpha1 chain bands appear if the patient is heterozygous
What are the consequences of the deformed collagen
Formation of bone.
Bone is formed by laying down hydroxyapatite (calcium phosphate) on an ordered scaffold of collagen-I.
Defects in the mineralisation process, leading to skeletal abnormalities and generally weak bones.
How is osteogenesis imperfecta diagnosed prenatally
Biopsy is impractical and risky on a foetus
Chorionic Villus Sampling (CVS) - screen the foetal DNA obtained
Amniocentesis which is amplified by PCR can also be used
Specific probes must be designed
What is anaphylaxis
IgE mediated acute type I hypersensitivity reaction to an allergen
Leads to shock (- blood pressure)
Can be systemic
Describe the normal response of IgE
parasitic infections
Antigen binds to IgM of lymphocytes
Proliferation
Th2 cells causes Ig switch to IgE
Binds to IgE receptors (FCεR1) on mast cells
mast cells degranulate on exposure to antigen
What are the effects of histamine
Vasodilation
Oedema (dyspnoea around the larynx)
Bronchoconstriction
Loss of blood volume (due to extravasation of fluid) leads to hypotension
Heart rate increases a bit but the force of contraction decreases
Contraction of smooth muscle in the walls of the intestines
What is urticaria
Type of rash characterised by red skin caused by vasodilation and raised skin caused by oedema
e.g. stinging nettle rash
Describe allergy testing
Small amounts of possible allergens are injected by pin-prick
It is then observed to see whether they cause a localised wheal-and-flare reaction
What is allergic rhinitis
Inhaled allergen causes mucosal mast cells to bring about oedema in the epithelia lining of the nose and mucous secretion
Describe asthma
Allergen reaches the bronchioles and the smooth muscle contracts
Inflammation and mucous production
Describe food allergies
Mucosal mast cells in the intestinal tract
Vomiting and diarrhoea
Pass into the bloodstream - skin symptoms
Why is the patient’s feet raised while lying down during anaphylaxis
Improve blood supply to the head and trunk
What is the treatment for anaphylaxis
Adrenaline - constricts peripheral blood vessels and directs blood to organs
IV - controls blood pressures
Antihistamines and anti-inflammatory corticosteroids
oxygen and bronchodilators
