MT1: Mats Short Answers

Question 1

1. Name the enzymes of this reaction (included picture of Choline + AcetylCoa → Ach + CoA)
2. Where is this enzyme located

Answer 1

1. Choline acetyltransferase

2. Presynaptic terminals of cholinergic neurons

Question 2

Indicate one therapeutical means by which the synthesis of NE can be decreased

Answer 2

AMPT
alpha-methyl-p-tyrosine

(used in adrenal medulla cancer)

Question 3

1. Which nT is released from the motor neurons stimulating contraction
2. Through which receptor is this effect mediated
3. What is the second messenger essential for the above effect

Answer 3

1. Acetylcholine
2. n-Ach-R
3. Increase in [Ca2+]ic

Question 4

List the consecutive intermediates in NE synthesis

Answer 4

L-tyrosine → DOPA → dopamine → NE

Question 5

How does dopamine influence the kidney:

1. The activity of the Na+/K+ ATPase
2. The rate of Na+ absorption

Answer 5

Dopamine is a natiuretic hormone:

1. Dopamine inhibits the basolateral Na+/K+ ATPase
2. Dopamine (→PKA) decreases activity of Na+/H+ exchanger (NHX) in the luminal membrane, thus decreasing Na+ entry into the cell

Question 6

Name the main metabolite formed in the brain in NE metabolism, which can be detected in urine

Answer 6

MHPG

3-methoxy-4-hydroxy-phenylglycol

Question 7

Name a hormone that stimulates the activity of the Na+/K+ ATPase

Answer 7

Aldosterone

Question 8

1. What is the name of the enzyme that hydrolyses Ach in the synaptic cleft
2. What kind of molecule exerts an irreversible inhibition on this molecule
3. What is the underlying clinical effect of this inhibition

Answer 8

1. Acetylcholinesterase
2. DFP (Diisoproylfluorophosphate) or other organic phosphate-molecules (mustard gas).
   The phosphate molecule covalently binds to the ser-residue of the active center
3. Inhibition of AchE will lead to accumulation of Ach in the synaptic cleft causing prolonged stimulation (paralysis) and eventually death (respiratory)

Question 9

1. What is the primary target of strophantine/oubain in the human body
2. What is the sequence of events that leads to positive inotropic effect by strophantine

Answer 9

1. Inhibits cardiac myocyte Na+/K+ ATPase
2. Accumulation of Na+ → NCX works in opposite direction → accumulation of Ca2+ → increased contractility

(too much leads to ↑↑Ca2+ which leads to tetanic contractions → death)

Question 10

Ion channels are protein pores that span the ….?

Answer 10

Plasma membrane

Question 11

The open probability of an ion channels range from/to?

Answer 11

From 0-100 % (Po = Time in open state / total observed time)

Question 12

At high ionic concentrations the ion channel throughput rates becomes …. ?

Answer 12

Saturated

Question 13

The protein segment responsible for the K+ channel selectivity is called the …?

Answer 13

Pore loop

Question 14

The selectivity filter of the K+ channel is located close to the …?

Answer 14

Extracellular side

Question 15

The central cavity communicates with which solution through the gate?

Answer 15

Incracellular solution

Question 16

During N-type inactivation the N-terminal peptide segment of the voltage-gated K+ channel plugs its pore from which side?

Answer 16

N-terminal is located on the intracellular side

Question 17

ATP-sensitive K+ channels are involved in the regulation of which hormone

Answer 17

Insuline secretion from Betacells (but also glucagon)

Question 18

Type II diabeetus mellitus can be treated by sulphonylureas.

What effect do they have on the ATP-sensitive K+ channels?

Answer 18

Sulfonylureas (tolbutamide) inhibits the ATP-sensitive K+ channels by binding to the SUR1-subunit. This leads to depolarization → Ca2+ → Insulin release

Question 19

What effect does phosphorylation by PKA have on the CFTR

Answer 19

Ser-residues in the intracellular regulatory domain are phosphorylated and activated. This is the physiological activator of the channel

Question 20

Under physiological conditions ATP-sensitive K+ channels are:

1. Activated by?
2. Inhibited by?

Answer 20

1. Activated by intracellular ADP (ic regulatory domains) and by diazoxide (TM region of SUR subunits)
2. Inhibited by high intracellular ATP (e.g. ↑glucose) → depolarization → Ca2+ → Insulin

(remember sulfonylureas also inhibits!)

Question 21

Which techniques reveals openings and closures of individual ion channel pores?

Answer 21

Patch clamp technique

Question 22

ATP-sensitive K+ channels are heterooctamers formed by four IRK-subunits (inward rectifying K-channel)
Which type are the last four receptor subunits?

Answer 22

Sulfonylurea receptor (SUR1, 2, 3 and 4)

Question 23

What does the phosphorylated CFTR channel need for gating?

Answer 23

ATP

Question 24

Why does ecstasy cause a drastic release in serotonin?

question is weird, but basically what does ecstasy do
Fenfluramide does the same

Answer 24

Ecstasy and Fenfluramide inhibits both the vesicle- and plasmamembrane transporter, leading to accumulation of serotonin in the cleft AND increased release from presynapstic

Question 25

Name an enzyme that makes NO, and what is it made from

Answer 25

Nitric Oxide Synthase (NOS), made from arg

Question 26

What is the action of phenylethanolamine N-methyl-transferase?

Answer 26

NE + SAM → E + SAH

Question 27

How does the AMPA receptor act on the NMDA receptor

Answer 27

AMPA alows Na+ influx → slight depol → Mg2+ is removed from NMDA → NMDA allows Na+ and Ca2+ influx → long-term and high depol

Question 28

What are the inhibitors of NE?

Answer 28

MAO and COMT

Question 29

What is the molecule that regulates the Ca2+ic directly?

Answer 29

IP3