Biochem: ACh

Question 1

Describe the synthesis of Acetylcholine (ACh).

Answer 1

Acetate from Acetyl CoA and choline obtained from diet (usually taken from cell membranes).

These two are combined by the enzyme Choline Acetyltransferase (ChAT)

Question 2

4 major sites in the CNS where neurons produce ACh.

Answer 2

Forebrain

1. Nucleus Basalis
2. Septal Nucleus
3. Nucleus of the Diagonal Band

Brainstem
4. Lateral dorsal & Peduculopontine nuclei

Question 3

Alzheimer’s disease is associated with decreased levels of ACh production. What is the hypothesis as to why this disease is associated with memory loss.

Answer 3

One of the major projection sites of the nucleus basalis and septal nucleus is to the hippocampus and mamillary bodies. These deal with forming memories.

Question 4

MOA of Botox.

Answer 4

Inhibits the action of snare proteins involved in NT vesicle fusion and release. Results in flaccid paralysis.

Question 5

MOA of Sarin gas.

Answer 5

Inhibits Acetylcholinesterase (AChase). Results in tetanic paralysis.

Question 6

Describe the signaling of the nicotinic and muscarinic cholinergic receptors.

Answer 6

Nicotinic
N1 - excitatory sodium channel on muscles
N2 - excitatory sodium channel on neurons

Muscarinic
M1,3,5 - excitatory Gq: increased IP3 + DAG
M2,4 - inhibitory Gi: decreased cAMP

Question 7

What is the mechanism of Lambert Eaton Syndrome (LEMS)?

Answer 7

Autoimmune disorder where the body creates antibodies against the voltage gated calcium channels on presynaptic neurons.

The calcium channels are necessary to signal the NT vesicles to bind to the snare proteins.

Question 8

What other condition is associated with LEMS?

Answer 8

Small Cell Lung Tumors

Question 9

What is the mechanism of Myasthenia Gravis?

Answer 9

The body makes autoantibodies against the Alpha-1 subunit of the N1 ACh receptor.

Question 10

What is the Tensilon Test?

Answer 10

Test to diagnose myasthenia gravis. The drug Edrophonium (AChase inhibitor) is given to patients which improves symptoms.

Question 11

Antidote to muscarinic excess or AChase inhibitor overdose (like Sarin Gas).

Answer 11

Atropine (muscarinic antagonist)

Question 12

Name two major histological characteristics of nerve cells in alzheimer’s patients.

Answer 12

1. Extracellular: amyloid beta peptide plaques

2. Intracellular: neurofibrillary plaques and tangles

Question 13

Disorder associated with Alzheimers.

Answer 13

Down Syndrome

Question 14

Describe the Amyloid Cascade Hypothesis.

Answer 14

It explains how the amyloid plaques are created in Alzheimer’s Disease and lead to the characteristic symptoms.

In general:

1. Intracellular calcium levels increase
2. This causes phosphorylation of the microtubule protein “Tau”
3. This forms the tangles and plaques