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Drugs and Disease > Transduction Systems 1 > Flashcards

Transduction Systems 1 Flashcards

1
Q

How are enzymes and second messengers involved in signal transduction?

A

The response involves a sequences of biochemical reactions usually carried out by ENZYMES
the biochemical reactions are linked through SECOND MESSENGER MOLECULES

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2
Q

What is a signal cascade?

A

the sequence of biochemical reactions that allows a stimulus to be amplified and sometimes expanded to produce multiple different responses

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3
Q

What are the most common second messengers?

A
  1. cyclic nucleotides
  2. calcium ions
  3. PIP3
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4
Q

What are cyclic nucleotides and what are some examples?

A

They are a derivative of ATP converted by the enzyme adenosine phosphate which removes two phosphates
examples are cyclic AMP and cyclic GMP

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5
Q

What is PIP3 and what can it be broken down into?

A

A phospholipid of the cell membrane that is converted by an enzyme into DAG (which stays in the membrane) and IP3 (released into the cell)

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6
Q

What do second messengers do?

A

Regulate the function of specific cellular effectors - KINASE or PHOSPHOTASE enzymes

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7
Q

In order for a stimulus to produce a response it must take advantage of the signal transduction pathway. How does it do this?

A

Through 4 primary types of receptors

  1. receptors linked to ion channels
  2. receptors coupled to G proteins
  3. receptors coupled to enzymes
  4. nuclear receptors
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8
Q

What is an example of a receptor linked to ion channels?

A

Ligand gated ion channels

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9
Q

What happens when a ligand binds to a receptor linked to an ion channel?

A

A pore in a membrane opens which increases the permeability of the membrane to Na+ K+ and Cl-

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10
Q

What happens when the movement of ions is increased due to the pore opening?

A

It affects a cellular response for example post synaptic excitatory or inhibitory response

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11
Q

How does the movement of ions through the opened more affect an ion channel?

A

Ion channels respond to the change in membrane potential - voltage gated ion channels

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12
Q

What causes the outside of the cell of be normally more positive than the inside?

A

It is a resting membrane potential due to the fact the Na+/K+ pump puts 3 Na+ out and 1 K+ in

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13
Q

How many subunits does a ligand gated ion channel have?

A

5 large multimeric protein subunits forms a pore

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14
Q

How fast acting are these channels and what different kinds of ion channels are there?

A 
Very rapid (milliseconds)
Cation channels (can't distinguish between K+ and Na+)
Chloride channels
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15
Q

What is signal transduction?

A

The process that allows the cell to convert an extracellular signal into a response

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16
Q

What is depolarisation?

A

Cell activation by cations

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17
Q

What is hyperpolarisation?

A

Cell inhibition by anions

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18
Q

What kind of movement is of the ions of these channels?

A

Passive movement - ill only move in the direction the gradient allows

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19
Q

In what kind of cells are these receptors found and what are some examples?

A

Fast responding cells e.g. on nerves and muscles where a response is instantaneous

20
Q

What is an example of a ligand gated ion channel?

A

Acetylcholine nictonic receptor

21
Q

An Ach nictonic receptor has 5 subunits, how many of them contain binding sites and what subunits are these?

A

2 of them and they are alpha subunits

22
Q

Where does the ligand bind and what does this do? (ANR)

A

Binds to both the alpha binding sites which opens the pore to allow Na+ ions to rush into the cell which causes muscle contraction

23
Q

What is tubocurraine?

A

An antagonist at acetylcholine receptors

24
Q

What kind of antagonist is tubocurraine?

A

A competitive, reversible antagonist

25
Q

What is tubocurraine?

A

An antagonist at acetylcholine nictotinic receptors

26
Q

What kind of antagonist is tubocurraine?

A

A competitive, reversible antagonist of acetylchlone

27
Q

How can tubocurraine be used in the modern world?

A

It is used to relax muscle during surgery as it blocks the affect of acetylcholine at nicotinic receptors and therefore causes muscle paralyses

28
Q

Tubocurraine is reversible; how is its affect overcome?

A

By increasing the concentration of acetylcholine

29
Q

To overcome tubocurraine you increase the concentration of acetylcholine; how would you do this?

A

By inhibition of the enzyme acetylchloineesterase which normally causes breakdown of acetylcholine by hydrolysis of the ester; if you inhibit acetylcholinesterase you then inhibit acetylchloine breakdown which increases the concentration of it allowing it to compete more with tubocurraine and reverse its effects

30
Q

Acetylcholine nictotinic receptors are an example of cation ion channels; what is an example of a chloride ligand gated ion channel?

A

GABAa Receptors

31
Q

What does GABA stand for?

A

Gamma Amino Butyric Acid (a neurotransmitter)

32
Q

What happens when the GABAa receptor ion channel is opened?

A

Cl- ions enter causing hyperpolarisation and cell inhibition

33
Q

Agonists that act on GABAa receptors therefore cause cell inhibition; what kind of drugs would want to target and activate these receptors?

A

Drugs that are used as sedatives, tranquillizers and also drugs used to treat seizures (anticonvulsants) such as diazepan

34
Q

What affect does alcohol have on the GABAa receptors?

A

It is an allosteric agonist and enhances the ability of the channel

35
Q

What is the structure of a G-Protein Coupled Receptor?

A

3 extracellular loops, 3 intracellular loops and 7 transmembrane domains

36
Q

Name two things about the extraceullar loops of the GPCR

A
  1. The loops are often glycosolated

2. They contain two cysteine residues which produce disulphide bonds to stabalise the receptor

37
Q

GPCR activates a G protein in order to produce a response; what is the structure of a G protein and where is it located?

A

It is a protein of 3 subunits (a, B, and y) attached to the membrane

38
Q

Which two of the three subunits of the G protein are closely associated

A

The b and the y subunits form a complex

39
Q

What is the function of the G protein subunits?

A

a contains GDP in its binding site and can activate an intracellular target (i.e. an enzyme) and the b/y complex can also activate an intracellular target (another enzyme)

40
Q

What are the steps involved in GPCR signalling?

A
  1. Agonist binds receptor
  2. The alpha subunit of the G-protein associates itself with the receptor, it has GDP bound to its active site
  3. The GDP of the alpha subunits active site is replaced by GTP which activates the subunit
  4. The GTP bound alpha subunit interacts and activates an enzyme while the b/y complex does the same
  5. The GTP of the alpha subunit is hydrolysed back to GDP by GTPase and the agonist leaves the receptor - everything returns back to the start
41
Q

Name 5 functions of the GPCRs?

A
  1. sensation
  2. behaviour
  3. immune system and inflammation
  4. metabolism
  5. autonomic nervous system
42
Q

Give an example of how GPCRs are used in sensation?

A

They are found in the retinas of the eye and respond to photons of light called opsins

43
Q

Give an example of how GPCRs are involved in behaviour?

A

They can be activated by neurotransmitters e.g. serotonin or dopamine which then lead to certain responds

44
Q

Give an example of how GPCRs are involved in the immune system?

A

Chemokine GPCRs are involved in the recruitment of immune cells to certain locations

45
Q

Give an example of how GPCRs are involved in inflammation?

A

Histamine GPCRs generate immune responses

46
Q

Give an example of how GPCRs are involved in metabolism?

A

GPCRs of the pancreas are used to sense gut hormone or dietary components in order to regulate glucagon and insulin secretion

47
Q

Give an example of how GPCRs are involved in the autonomic nervous system?

A

The sympathetic nervous system uses adrenoceptor and the parasympathetic uses muscarinic receptors to mediate their effects

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