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BMS2002 > L13 > Flashcards

L13 Flashcards

1
Q

what are the 3 stages of signal transduction

A

an extracellular signal molecule activates a membrane receptor (stage 1)

that in turn alters intracellular molecules to be transduced via a certain pathway (stage 2)

to activate a cellular response (stage 3)”

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2
Q

what is the first messenger

A

The extracellular signal molecule

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3
Q

what is second messenger system

A

a system formed by intracellular molecules

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4
Q

what are transducers

A

membrane proteins in between first and second messenger system that convert the message of extracellular signals into intracellular messenger molecules that trigger a response

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5
Q

what are the Types of response in signal transduction

A

altered ion transport

altered metabolism

altered gene expression

altered cell shape or movement

altered cell growth and division

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6
Q

what chemicals can serve as extracellular signalling molecules? give examples

A

Amines (e.g. epinephrine, adrenaline)

Peptides & Proteins (e.g. angiotensin II, insulin)

Steroids (e.g. hormones)

Other small molecules (e.g. amino acids, ions, gases)

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7
Q

what are the differences between cell surface and intracellular receptors interaction

A

molecules that bind trans membrane receptors can’t cross the plasma membrane

nuclear receptors are hydrophobic and mostly act as transcription factors and give a slow response

Membrane receptors are hydrophilic and signaling molecules activate a wide variety of intracellular “signal transduction” pathways (e.g. ion-channels, G proteins coupled receptors and catalytic receptor), including gene regulation. they give a fast response

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8
Q

what are the types of receptors

A

Ligand-gated ion channels

G-protein coupled receptors

Enzyme-linked receptors

Nuclear receptors

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9
Q

what receptors give rise to the fastest response

A

Ligand-gated ion channels

then G protein channels

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10
Q

what are Ionotropic receptors

A

receptors that are ion channels

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11
Q

give examples of Ionotropic receptors

A

Nicotinic acetylcholine receptor

The gamma-amino buytyric acid (gaba)A receptor

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12
Q

what are the features of Nicotinic acetylcholine receptor

A

Ligand gated ion channel that mediates effects of acetylcholine (ACh) on muscle etc

Binding of acetylcholine between alpha and delta subunits opens a channel and allows Na+ entry

Binds nicotin

Electrical event (inward Na+ current) triggers response

Calcium may also enter from this channel

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13
Q

what are the features of The gamma-amino buytyric acid (gaba)A receptor

A

selective for Cl- ions

Naturally activated by g-\amino butyric acid – CNS neurotransmitter

Inhibitory receptor

Very important role in CNS

Activated by benzodiazepines

Also by alcohol and anesthetics

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14
Q

what are Benzodiazepines

A

sedative drugs that activate The g-amino buytyric acid (gaba)A receptor

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15
Q

what are Metabotropic receptors

A

receptors that are not ion channels but cause the opening of ion channels. they are indirectly linked with ion channels on the plasma membrane through signal transduction pathways, generally G proteins mediated

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16
Q

give examples of Metabotropic receptors

A

Muscarininc

Gaba B

17
Q

what are the features of Muscarinic receptors

A

activated by ACh

More sensitive to muscarine than nicotine

18
Q

what are the features of Gaba B receptors

A

activates a Potassium channel

More sensitive to muscarine than nicotine

19
Q

what are the features of G protein coupled receptors

A

Receptors that activate G proteins all have 7 transmembrane domains

At least 800 genes encode G protein coupled receptors

20
Q

what are the polypeptide chains of g proteins

A

alpha, beta and gamma

21
Q

how many subunits are there for each G protein polypeptide

A

16 alpha subunits,

5 beta

11 gamma

22
Q

what 2 G protein subunits bind tightly, effectively forming a single subunit

A

beta and gamma

23
Q

what subunit has a guanine nucleotide binding site that binds GTP or GDP

A

alpha

24
Q

compare alpha GDP and alpha GTP

A

alpha-GDP has high affinity for beta gamma (resting conditions)

alpha-GTP has low affinity for beta gamma

25
Q

which subunit can hydrolyze GTP

A

alpha

26
Q

whare is the G protein complex located

A

inside plasma membrane

27
Q

what are the steps in the G protein cycle

A

e.g.

Adrenaline binding to beta-adrenoceptor

Allows b-adrenoceptor / G protein interaction

GDP on alpha subunit is exchanged for GTP

Allows alpha subunit liberation

Free a subunit activates adenylyl cyclase AC

activated AC generates cAMP by hydrolising ATP

Unbinding of adrenaline /
GTP hydrolysis (1 GTP hydrolysed each time ‘round cycle)

28
Q

what does cAMP do

A

activate Protein Kinase A (PKA)

29
Q

what are the features of PKA

A

PKA is a tetrameric protein with two types of polypeptide chains Catalytic (C) and regulatory (R)

Inactive PKA - subunits bound together and R subunit suppresses activity of C subunit

R subunits have 2 binding sites for cAMP

cAMP binding allows the subunits to dissociate

Catalytic subunits become active….phosphorylate other proteins.

PKA catalyzes transfer of ATP to specific serine or threonine residues on substrate proteins

30
Q

what physiological responses are mediated by cAMP / PKA

A

Kidney collecting duct – activated by vasopressin and stimulates water retention

Vascular smooth muscle and Cardiac muscle – activated by adrenaline and promotes relaxation/increase heart rate

Colonic epithelium – activated by various factors and promotes fluid / electrolyte secretion

Pancreas –activated by glucagone and promotes release of glucose in the blood

31
Q

how can the G protein cycle end

A

Removal/inactivation of signal

Removal/inactivation of receptor

Inactivation of activated signalling proteins
- GTP hydrolysis
- dephosphorylation

Degradation/removal of second messengers

32
Q

hew is the removal of second messengers achieved

A

cAMP is hydrolysed by phosphodiesterase (PDE)

When hormone is removed, PDE rapidly clear cAMP from the cell

Unbinding of cAMP from R subunit increases affinity for C subunit

Protein reassembles into tetramer and are inactivated

PDEs are inhibited by caffeine. Interfering with a “switch off” mechanism prolongs the time on and indeed prolongs a cellular response

33
Q

how is desensitization of receptor achieved

A

(1) Protein phosphorylation
leads to cellular response
(e.g. Glucose release)

(2) PKA phosphorylates beta-ARK and increases activity

(3) beta-ARK phosphorylates b-adrenoceptor and reduces affinity for adrenaline

(4) Reduced affinity leads to reduced cellular response despite sustained stimulation

34
Q

what protein does Dephosphorylation

A

Protein phosphatases

35
Q

what molecule is never part of the G protein signaling

A

GABAA

BMS2002 (14 decks)

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