Topic 1, Key Area 4

Task 57

Watch the video (from 31min 25s) about Parkinson's disease and read the information about the disease (below), along with your own research. Give a brief summary of the condition and explain how alterations to cell signalling lie at the heart of the physiological manifestations of the disease.

In healthy mitochondria, a signalling pathway involving a protein called PINK1 is inactive. However, it mitochondria become damaged, PINK1 accumulates and phosphorylates another protein, called Ubiquitin. Phosphorylation of ubiquitin leads to the recruitment of a protein called Parkin, which also undergose phosphorylation. This activates the pathway and long ubiquitin chains build up in the cell. These chains are receptors for proteins involved in the removal of damage - the cell then digests its own contents. The mitochondria are eliminated. This is a pathway in ALL cells of everyone. But, in patients with Parkinson's disease, it is thought that their mitochondria are more susceptible because these neurons are more metabolic due to mutations in PINK1 and Parkin. The neurons cannot renew and once damaged and removed, that's that.

Ultimately, Parkinson's disease is thought to result from alterations in key signalling pathways that result in the destruction of neurons.

Task 58

Given what you know about hydrophobic and hydrophilic molecules and the cell membrane, how might such molecules transduce their messages across the membrane to give an intracellular response?

Suggested response: Hydrophobic molecules would be able to cross the membrane and so might pass across and cause an effect inside the cell directly. Hydrophilic molecules cannot enter the cell so probably bind to a receptor and cause an effect indirectly.

Task 59

Try and complete the diagram in your notes for Task 59 using the statements in the yellow boxes to help you.

Task 60

Using the information above, together with the animation linked below, to produce a flowchart and diagram to illustrate the action of thyroxine.

Task 61

Sort the statements into 2 columns: Hydrophilic signalling molecule OR hydrophobic signalling molecule.

Task 62

Watch the following video and write a step-by-step guide to summarise the role of G proteins in transducing extracellular hydrophilic signalling molecules into intracellular responses.

Task 63

Make your own notes for this task.

Task 64

Using information presented in the two figures, can you explain the results observed for the "Normal", "impaired" and "Type 2 Diabetes" patient.

In the normal patient, under fasting levels when they arrive at the clinic, their blood glucose concentration is <6mmol/L. Two hours after the glucose drink, their blood glucose level remains low and definitely less than the 7.8 mmol/L suggested by the GTT test guidelines. This is because there was an immediate insulin increase in the "normal" patient, which peaked within an hour of glucose consumption, which was effective at maintaining normal blood glucose concentration.

By contrast, the person with impaired glucose homeostasis arrived in the clinic with the same blood glucose concentration as a normal person. However, upon consuming glucose, their insulin levels increased dramatically with limited impact on their blood glucose concentration. After 2hrs, their blood glucose concentration was still elevated at around 8.8 mmol/L.

In a person with diabetes, their fasting blood glucose concentration is already elevated compared to a "normal" patient. Consumption of glucose leads to a long steady increase in blood glucose concentration with a disproportionate and very delayed increase in insulin production. The production of insulin does not have a significant impact on the patient's blood glucose levels and, 2 hours after consumption of glucose, the blood glucose concentrations remain very high at 13 mmol/L.

Task 65

Make sketches of "the basic structure of a neuron" (left) and "a close-up view of a synapse" (right).

Explain what must happen for the nerve impulse in a pre-synaptic neuron to be transmitted to a post-synaptic neuron - for this to happen, the nerve impulse might trigger the release of a neurotransmitter from a vesicle, within the axon of the pre-synaptic terminal, into the synaptic cleft. This neurotransmitter diffuses across the cleft until it docks with a receptor on the post-synaptic neuron.

Task 67

Sketch a graph to show the changes in membrane potential during impulse transmission along a nerve axon. Explain the effect of ligand-gated and voltage-gated ion channels on the membrane potential of a neuron during neurotransmission.

Task 68

Read the statements shown about nerve impulse transmission and put them in the correct order.

1. A neurotransmitter acts as a ligand and opens ligand-gated ion channels in the neuron membrane.

2. This allows sodium ions to enter the neuron and the membrane becomes depolarised.

3. A threshold change in voltage triggers the opening of voltage-gated sodium channels.

4. The neighbouring area along the axon becomes depolarised as voltage-gated ion channels now open further along the axon.

5. Depolarisation eventually results in the opening of voltage-gated potassium channels. Potassium floods out of the neuron.

6. Repolarisation occurs and eventually the resting membrane potential is maintained by the Na/K pump.

Task 69

Can you label the diagram of the vertebrate eye in your own notes?

Task 70

The diagram below summarises signal transduction in rod cells of the vertebrate retina. Can you provide a text-based summary to describe what is happening?

A photon of light is absorbed by retinal, the light-absorbing component of rhodopsin. A conformational change takes place in the membrane protein and it becomes activated. This activates the G-protein called transducin. Many copies of transducin become activates, each activating a phosphodiesterase molecule. These activate PDE molecules hydrolyse cGMP, which acts to remove the ligand from sodium channels in the membrane. This prevents the influx of sodium ions into the cell, changing the membrane potential. A nerve impulse results.