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week 5 Flashcards

1
Q

define enzymes

A

catalyse a particular reaction, leaving the enzyme unchanged

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2
Q

define catabolic

A

breakdown

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3
Q

define anabolic

A

synthesis

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4
Q

example of anabolic reaction = acetylcholine

A
  1. Synthesis of acetylcholine (choline acetyltransferase)
  2. Acetylcholine is packaged in vesicle (the yellow) up to leave the axon
  3. Acetylcholine leaves the neuron & begin to cross the synapse
  4. Acetylcholine reaches the other side of the synapse & binds to the receptor causing the message to be sent
  5. After the message is sent, acetylcholine is released back into the synapse
  6. Acetylcholinesterase (enzyme) breaks down acetylcholine, inactivating it
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5
Q

irreversible inhibitors of Acetylcholinesterase & effect

A
  • chemical warfare agents e.g., sarin gas
  • insecticides e.g., parathion

= build up of acetylcholine = toxic

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6
Q

reversible inhibition of Acetylcholinesterase & effect

A
  • donepezil = inhibits enzyme = increase drug in brain = helps with memory = helps with Alzheimer’s disease
  • pyridostigmine
  • rivastigmine
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7
Q

define false substrate

A

binds to enzymes but not actual substrate = disrupts normal metabolic pathway

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8
Q

what are the four superfamilies of receptors & fast to slowest & location

A
  1. ligand-gated ion channels (ionotrophic receptors) = cell membrane
  2. protein coupled receptors (metotrophic) = cell membrane
  3. kinase-linked receptors = cell membrane (some intracellular)
  4. nuclear receptors = intracellular (class I = cytoplasm, class II = nucleus)
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9
Q

define ligand

A

bind to receptor & can be antagonist

e.g., hormones, neurotransmitters, growth factors

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10
Q

example of ligand gated ion channel

A

nicotinic acetycholine receptor, GABA A, Nicotonic, NMDA receptors

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11
Q

example of receptor: ligand gated ion channel

A

nicotinic acetycholine receptor, GABA A, Nicotonic, NMDA receptors

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12
Q

example of ligand for: ligand gated ion channel & is it an agonist, antagonist or allosteric modulator

A

GABA, acetycholine, glutamate = agonist & benzodiazepines are allosteric modulators

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13
Q

what is the effector of each receptor superfamily

A
  1. ion channel
  2. enzymes & ion channels
  3. protein kinases
  4. gene transcription related molecules (e.g., transcription factors)
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14
Q

structure of ligand gated ion channel receptor

A

oligomeric (4-5 subunits) combined to form pore in the middle)

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15
Q

define coupling

A

is the effector & the receptor the same macromolecule

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16
Q

ligand gated ion channel: coupling?

A

direct - ion channel part of the receptor

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17
Q

example of receptor: G protein-coupled receptor

A

adenosine, adrenergic receptors

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18
Q

example of ligand: G-protein-coupled receptor & is it an agonist, antagonist or allosteric modulator

A

caffeine & adrenaline/noradrenaline

= every ligand agonist except caffeine which is an antagonist

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19
Q

structure of G-protein-coupled receptor

A

mono or oligomeric 7-TM with a G protein coupling site

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20
Q

G-protein-coupled receptor: coupling?

A

indirect - transducer = g protein & arrestin

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21
Q

what activates the effector in G protein coupled receptor

A

via G proteins or arrestins

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22
Q

what are the three subunits of a G-protein coupled receptor

A

alpha, beta, gamma = takes message from receptor to effector = transducer

  • beta, gamma unit separates from alpha when binds & alpha activates effector depending on specific alpha type
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23
Q

three types of alpha subunits & what they do

A

Gas = stimulates = enzyme works better

Gai = inhibits enzymes

Gaq = increase calcium

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24
Q

main effector for Gas & Gai

A

Adenylyl cyclase (AC) = the enzyme responsible for the production of cAMP (second messenger) = intracellular signal induction

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25
main effector for Gaq
phospholipase C = enzyme responsible for inositol triphosphate (IP3) & diacylglycerol (DAG) formation (they are second messengers)
26
DAG activates...
protein kinase C
27
IP3 releases..
release stored calcium into cytoplasm
28
define desensitisation in G-protein coupled receptor
the decreased responsiveness that occurs with repeated or chronic exposure to agonist
29
define trafficking of G-protein coupled receptor
an active process in which proteins are re-located from one region of a cell to another
30
example of receptor: kinase-linked receptors
insulin, growth factors, cytokine receptor
31
example of ligand: kinase-linked receptor & is it an agonist, antagonist or allosteric modulator
insulin, endothelial growth factors = agonist
32
structure of kinase-linked receptors
single transmembrane helix linking extracellular receptor domain to intracellular kinase domain
33
kinase-linked receptor: coupling?
direct (no need to couple-kinase part of the receptor)
34
what does activation of kinase-linked receptors alter
alters cell transcription
35
role of kinase-linked receptors
protein mediators e.g., cytokines, cross phosphorylation by dimerise = cascade of cellular events
36
structure of nuclear receptors
monomeric structure with a DNA binding domain
37
example of receptor: nuclear receptor
steroid receptor
38
example of ligand: nuclear receptor & is it an agonist, antagonist or allosteric modulator
glucocorticoids, oestrogen, testosterone = agonist
39
nuclear receptor: coupling?
indirect via DNA
40
role of nuclear receptors
ligand-gated transcription factors = regulate gene transcription = ability to enhance or repress the expression of a gene in response to changes in the environment
41
occurence after ligand binds to nuclear receptor
form homodimers or heterodimers & translocate to the nucleus where can transactivate or transpress genes
42
define transactivate
increase transcription
43
define transpress
decrease synthesis
44
what does the receptor-ligand complex bind to
binds to hormone response elements in gene promoters & recruiting co-activator or co-repressor factors
45
define homodimers
made from to identical proteins
46
define heterodimers
made from to two difference proteins
47
attachment of nucleus receptor complex
direct or indirect, directly on the transcription or on the transcription factors
48
can all types of receptors be allosteric modulated
yes
49
define functional selectivity aka bias agonism
different drugs binding at the same receptor one has more of a response These two drugs can cause different physiological effects because one drug is biased towards one pathway while the other drug is biased towards the other pathway.
50
role of transporters as a drug target
important for the transport of molecules that are insufficiently lipid-soluble to penetrate lipid membrane on their own
51
what do transporters transport
transport ions, many organic molecules across the renal tube, the intestinal epithelium & the blood brain barrier
52
define rate limiting step
slowest step out of all steps that occur for a given metabolic pathway/chemical reaction e.g., choline transporter is the slowest step due to limited choline transporters
53
two types of transporters & subtypes
1. passive transport (passive diffusion & facilitated diffusion) 2. active transport a. secondary active transport = symport & antiport b. primary active transport = primary site transport (site where ATP binds)
54
what is the sodium potassium pump
= helps to maintain osmotic equilibrium and membrane potential in cells. - the sodium and potassium move against the concentration gradients
55
types of transporters
- sodium potassium pump - solute carriers superfamily - ABC transporters
56
what are solute carriers SLC
facilitate transport of substances down their electrochemical gradient
57
what are ABC transporters
transport substances against electrochemical gradient by using the energy provided by the hydrolysis of ATP
58
what does ABC stand for in ABC transporters
ATP-binding cassette
59
example of ABC transporter
P-glycoprotein transporters
60
how do transporter inhibitors work
increase neurotransmission by inhibiting the reuptake of drugs - the drug then increases in concentration in the synapse = toxic
61
the two categories of drugs that affect the CNS
1. antidepressants | 2. psychomotor stimulants
62
three antidepressants
1. selective serotonin reuptake inhibitor (SSRI) 2. serotonin & noradrenaline reuptake inhibitor (SNRI) 3. tricyclic antidepressants (TCA)
63
three psychomotor stimulants
1. cocaine (inhibits, 5-HT (serotonin), NA (narcotics) & DA (dopamine) reuptake 2. amphetamine & related compounds (inhibition of DA & NA uptake) 3. MDMA (ecstasy) (inhibits uptake 5-HT = serotonin)
64
role of messengers
stimulated by agonists = IP3, DAG, calcium ions

phar24 (12 decks)

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