Exam I: Neurochem

Question 1

Criteria for a molecule to be considered a neurotransmitter.

Answer 1

1. Must be synthesized and stored in the presynaptic neuron
2. Must be released upon stimulation of the presynaptic neuron
3. After it is released, it must produce a response in the post synaptic cell (can be another neuron or effector cell)
4. Must be a mechanism of elimination (via metabolism, reuptake, or diffusion which is very slow)
5. Must be a well-defined post synaptic receptor for the neurotransmitter than will produce a pharmaco-relevant response

Question 2

Nicotinic acetylcholine receptors reside on what type of channels?

Answer 2

Ligand-gated ion channels

Question 3

Describe the structure of a g protein-coupled receptor in relation to its mechanism of action.

Answer 3

One extracellular domain where the neurotransmitter will bind

Seven transmembrane domains,

One intracellular domain (changes the concentration of second messengers – increase or decrease depending on the type of neurotransmitter or receptor used)

Question 4

cAMP, cGMP, Ca2+, IP3, DAG are examples of?

Answer 4

Secondary messengers

Question 5

Name 5 monoamine neurotransmitters.

Answer 5

1. Norepinephrine
2. Epinephrine
3. Histamine
4. Dopamine
5. Serotonin

Question 6

Name 2 amino acid neurotransmitters.

Answer 6

1. GABA

2. Glutamate

Question 7

Describe acetylcholine solubility. Why?

Answer 7

Acetylcholine is highly water soluble due to the positive charge on the nitrogen

Question 8

Can acetylcholine be given directly to a patient to increase cholinergic activity? Why or why not?

Answer 8

No, acetylcholine cannot be given directly to a patient.

Esterase is ubiquitous and in high abundance in the body. Ach will never be able to reach a cholinergic receptor.

Carbamate with NH2 instead of N(CH3)3 must be given to increase cholinergic activity.

Question 9

Explain how organophosphates (ie. nerve gas) are toxic.

Answer 9

Can be used as herbicides.

Lipophilic structure makes the molecule volatile.

Can enter the body and reach neuron synapses

Acetylcholine esterase reacts with the organophosphate to form a phosphate ester (longer half life than acetylcholine)

Acetylcholine accumulates because majority of AchE is reacting with the organophosphate

Organophosphate-complex bound to postsynaptic nicotinic receptors can cause paralysis and death.

Question 10

What is the antidote for nerve gas toxicity? How does it work

Answer 10

Atropine is an anticholinergic that can bind to muscarinic acetylcholine receptors and prevent acetylcholine from binding.

This can alleviate some of the problems associated with nerve gases.

Question 11

What kind of receptors are muscarinic cholinergic receptors?

Answer 11

G protein coupled receptors

Question 12

3 catecholamines

Answer 12

Dopamine

Epinephrine

Norepinephrine

Question 13

Which amine is more basic, epinephrine or norepinephrine?

Answer 13

Epinephrine with the primary amine

Question 14

Is the hydroxy group beta to the amine group acidic or basic in epinephrine and norepinephrine?

Answer 14

Neutral

Neither basic nor acidic

Question 15

On the catechol group in norepinephrine, are the hydroxy groups acidic or basic?

Answer 15

Phenolic hydroxy is acidic (pka 9, pka 12 after the first hydrogen is donated – harder to take the last hydrogen)

Question 16

Solubility of epinephrine and norepinephrine.

Answer 16

Highly water soluble – two hydroxy groups and amine that can contribute to hydrogen bonding

Question 17

Difference between alpha and beta adrenergic receptors?

Answer 17

Differ by agonist activity

Alpha - epinephrine > or equal norepinephrine&raquo_space;> isoproterenol

Beta - isoproterenol > epinephrine > or equal norepinephrine

Question 18

What two ways can adrenergic receptors be deactivated?

Answer 18

A. Catechol-O-methyltransferase (COMT) - adds methyl group onto the meta hydroxy on norepinephrine or epinephrine which deactivates adrenergic receptors.

B. - 1. MAO (monoamine oxidase) 2. Aldehyde dehydrogenase. Removes amine group in first step. Second step adds a carboxylic acid to the molecule in the place where the amine group was.

Combination of the two can also be used to deactivate adrenergic receptors

Question 19

Enzyme that catalyzes the reaction of acetyl coa and choline to acetylcholine.

Answer 19

Choline acetyltransferase

Question 20

Enzyme that catalyze the degradation of acetylcholine

Answer 20

Acetylcholine esterase

Question 21

4 reactions that make epinephrine from L-tyrosine.

Answer 21

1. L-tyrosine (tyrosine hydroxylase) —> Levodopa L-DOPA
2. Levodopa (Dopa decarboxylase) –> Dopamine
3. Dopamine (Dopamine beta-hydroxylase) –> Norepinephrine
4. Norepinephrine (N-methyl transferase in adrenal medulla) –> Epinephrine