Week 5 TBL Flashcards

(107 cards)

1
Q

Prostaglandins are involved in what?

A
Carcinogenesis
Bone remodelling
Sleep 
Inflammation and pain
Allergy and immunity
Vascular homeostasis and haemostasis
Fever generation
Ovulation, fertilisation and parturition
Gastrointestinal function
Renal function
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2
Q

How do prostaglandins act?

A

5 basic types of receptor
Called P receptors and preceding letter indicated the natural prostanoid to which each receptor is most sensitive
e.g. EP, DP, DF
Subscript numerals indicate that receptor has subtypes e.g. EP1, EP4

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3
Q

IP receptor binds what?

What does it mediate?

A

PGI2

  • vasodilation
  • inhibits platelet aggregation
  • Fibrinolysis
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4
Q

What are prostaglandins?

A

Polyunsaturated, oxygenated derivatives of three C20 fatty acids (AA, DGLA, EPA)

Classified into10 types (PGA-PGJ) according to:

  • the code of ring variants (A-J) and
  • number of double bonds in their side chain (1-3)
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5
Q

If R1 is a carbonyl and R2 is a hydroxyl group.
and the whole structure has 2 double bonds
What name of prostaglandin is it?

A

E2

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6
Q

IF R1 us a hydroxyl group and R2 us a carbonyl group
and the whole structure has 2 double bonds
What name of prostaglandin is it?

A

D2

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7
Q

If both R1 and R2 are hydroxyl groups
and the whole structure has 2 double bonds
What name of prostaglandin is it?

A

F2(alpha)

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8
Q

What is PGE2 involved in?

A

inflammatory

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9
Q

What is PGD2 involved in?

A

immunity

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10
Q

What is PGF2(alpha) involved in?

A

vasoconstriction

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11
Q

What is PGI2 involved in?

A

Potent vasodilator that inhibits platelet aggregation

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12
Q

What is a prostanoid?

A

Prostanoids are a subclass of eicosanoids consisting of the prostaglandins (mediators of inflammatory and anaphylactic reactions), the thromboxanes (mediators of vasoconstriction), and the prostacyclins (active in the resolution phase of inflammation.)

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13
Q

What is TXA2?

A

Thromboxane A2

a potent inducer of platelet aggregation

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14
Q

Draw Prostaglandin E?

A

ok

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15
Q

Draw Prostaglandin F?

A

ok

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16
Q

Draw Prostaglandin D?

A

ok

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17
Q

What are prostaglandins made of?

A
20C fatty acids 
Major substrate = ARACHIDONIC ACID (AA) (gives rise to ‘2’ series PG)
But can also be derived from: 
   Dihomogamma-linolenic acid (DGLA) 
   (‘1’ series PG) or
   Eicosapentaenoic acid (EPA) 
   (‘3’ series PG)
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18
Q

When DGLA is the precusor molecule, how many double bonds are in the resulting prostaglandin?

A

One

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19
Q

When arachodonic acid is the precusor molecule, how many double bonds are in the resulting prostaglandin?

A

Two

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20
Q

When EPA is the precusor molecule how many double bonds are in the resulting prostaglandin?

A

Three

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21
Q

How many double bonds in DGLA?

A

Three

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22
Q

How many double bonds in AA?

A

Four

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23
Q

How many double bonds in EPA?

A

Five

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24
Q

What kind of enzyme adds carbons?

A

elongase

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25
What kind of enzyme adds double bonds?
Desaturase
26
Which pathways involve our cells all the time with regards to eiconasoids?
Fatty acid pathways omega-3, omega-6 and omega-9
27
EPA is what omega?
Omega-3 fatty acid
28
AA is what omega?
Omega-6 fatty acid
29
DGLA is what omega?
Omega-6 fatty acid
30
Omega means?
The end | Omega 3= double bond 3 carbons from the end
31
What are the essential fatty acids?
``` alpha-linolenic acid (ALA) linoleic acid (LA) ```
32
What will happen to your body if you have no fat?
- Skin red, unstable | - disorders that come from essential fatty acids
33
Why are they called essential fatty acids?
Mammals cannot make them, we must take them from our diet
34
Nutrients needed for ALA
flaxseed, rapeseed, soy oils
35
ALA is the start of which pathway?
omega-3
36
LA is the start of which pathway?
omega-6
37
Nutrients needed for LA
safflower, cottonseed, soy, cornoils
38
Why do people eat fish for brain power?
DHA is at the end of the omega-3 pathway and is used for brain-power Babies are born with the correct amount of DHA (from their mothers) in their nervous system in the omega-3 only a small amount (less than 5%)of ALA is converted to DHA and EPA hence fish can increase the amount of EPA and then hence the amount of DHA --> brain power! Having a lot of plant oils will not give you the amount of DHA you need
39
What things can you eat to increase the amount of EPA in the omega-3 fatty acid pathway?
oily fish fish oils krill oil algae
40
What things can you eat to increase the amount of gamma linoleic acid at the start of the omega-6 pathway?
borage and evening primrose oils
41
What things can you eat to increase the amount of DGLA in the omega-6 pathway?
liver, organ meats
42
What things can you eat to increase the amount of AA in the omega-6 pathway?
animal fats, butter, egg yolks
43
Full name of DGLA | (‘1’ series PG)
Dihomogamma-linolenic acid
44
Full name of EPA? | 3 series PG
Eicosapentaenoic acid
45
Full name of AA? | 2 series PG
Arachodonic acid
46
What does a phospholipase enzyme do?
Convert membrane-bound phospholipid into Arachodonic acid
47
What inhibits a phosopholipase enzyme?
Corticosteroids
48
What does a COX enzyme do?
Convert AA to the Cyclic endoperoxides i.e. PGG2 and PGH2
49
What inhibits a COX enzyme?
Coxibs and NSAIDs
50
What does COX stand for?
Cyclooxygenase
51
What does NSAID stand for?
Non-steroidal anti-inflammatory drug
52
The cyclic endoperoxides PGG2 and PGH2 go on to make what important molecules?
``` PGD2 PGE2 PGF2 PGI2 TXA2 (Thromboxane) ```
53
What do prostaglandins generally mediate?
mediators of inflammatory and anaphylactic reactions
54
What do prostacyclins generally do?
They're active in the resolution phase of inflammation
55
What do thromboxanes do?
Mediators of vasoconstriction
56
True or false, AA is toxic in high concentrations | Why/why not?
True it also explains why AA is metabolised by COX1 immediately after being cleaved why PLA2. It is not free in the cell.
57
What does PLA2 do?
Phospholipase A2 frees (cleaves) arachodonic acid from the cell
58
NSAIDs inhibit what enzyme?
COX (cyclo-oxygenase)
59
How do cyclooxygenases make Prostanoids?
Cox1 and cox2 work one after the other once AA is released from the membrane Cox transforms AA to unstable intermediate(s) And then depending where the reaction takes place and what the system wants, other prostaglandins are made
60
Too much prostaglandin being made uncontrollably can stimulate activity, causing health issues such as...? PGE2 and COX2 over expression
Cancer
61
Cancer has overexpression of what?
COX2 enzyme | PGE2
62
Why are coxibs bad? What do they do?
Specialist inhibitors of COX2 Side effect was cardiovascular disease people in clinical trials had heart attacks COX2 also needed in CVS
63
Difference between the isoforms COX1 and COX2
COX-1 - constitutive - in all cells, does basic housekeeping COX-2 - induced (by cytokines, inflammatory stimuli, induced when cells need a lot of PGs) If you don't switch it off then there will be inflammation etc
64
low levels of COX-1 needed for
homeostasis, vital for cell function
65
Some cell types need COX2 such as
CVS cells
66
When a physiological stimulus is there, what happens to AA?
``` COX-1 pathway activated -TXA2 and PGI2 made Control of platelet aggregation and vascular tone -PGE2 also made Cytoprotection ```
67
What happens when PGs are no longer needed?
They are metabolised by other enzymes in the body into inactive metabolites Uncontrolled overexpression of PGs you get inflammation that cannot resolve
68
Uncontrolled overexpression of PGs you get what?
Inflammation that cannot resolve
69
What is a knock-out mice model?
mice bred so certain information is removed from the genome | e.g. COX2 knockout mice have no COX2 enzyme
70
Phenotypic changes in COX1 knockout mice?
- reduced platelet aggregation - Decreased amino acid-induced inflammation - sensitive to radiation injury - resistant to indomethacin-induced gastric ulceration
71
Phenotypic changes in COX2 knockout mice?
- Defective ovulation, fertilisation, implantation, decidualisation - Decreased brain injury induced by ischaemia - supression of tumourgenesis - renal nephropathy - cardiac fibrosis - peritonisis - failure of patent ductus arteriosus closure
72
How many domains does a GPCR have?
Seven
73
How many types of prostaglandin are there?
5
74
PG receptors are...
G-protein coupled transmembrane receptors | Linked to cAMP and/or Ca2+ signalling
75
AA is converted to PGG2 via COX | What does PGG2 make?
PGH2
76
PGH2 activates what GPCR transmembrane domains?
``` PGI2 PGD2 PGE2 PGF2alpha PGF2 TXA2 PGD2 ```
77
How many receptors are used by PGE? | Why?
Four (EP1, EP2, EP3, EP4) For ten properties
78
Complete this | DP receptor binds ___ and mediates what?
PGD2 - vasodilation - inhibits platelet aggregation - GI relaxation
79
FP receptor binds ___ and mediates....
PGF2(alpha) - luteolysis (degradation of corpus luteum in menstral cycle) - bronchoconstriction
80
IP receptor binds ___ and mediates...
PGI2 - vasodilation - inhibits platelet aggregation - fibrinolysis
81
TP receptor binds ___ and mediates..
TXA2 (Thromboxane) - vasoconstriction - platelet aggregation - bronchoconstriction
82
What does the EP1 receptor mediate?
GI contraction | Pyrexia (fever)
83
What does EP2 receptor mediate?
bronchodilation vasodilation stimulates GI fluid secretion
84
What does EP3 receptor mediate?
GI relaxation inhibition of gastric acid secretion inhibition of ANS transmitters pyrexia
85
What does EP4 receptor mediate?
vasodilatation bone homeostasis pyrexia
86
Methods of relatting PGs to therapeutics?
substrate substitution enzyme inhibitors prostaglandin replacement therapy/use of synthetic, selective analogues
87
If you change your diet to eat less meat and more fish, what will happen?
Less omega-6 fatty acids produced (therefore less and DGLA AA) More omega-3 fatty acids produced (therefore more EPA) This will produce an anti-inflammatory environment Not to trigger baseline inflammatory conditions
88
GLA comes from primose oil | what effect?
Calming effect as it promotes more PG1 instead of PG2
89
fish oil in diet is good because...
Fish oil is rich in DHA and EHA | it promotes PG3 instead of PG2
90
Omega-3 fatty acids were significant in clinical trails because fish oil supplementation resulted in
reduction of fasting blood triglycerides | (but not total HDL or LDL cholesterol) in hyperlipidaemic subjects
91
in only one condition Coxibs are still used | Which? Why?
Arthritis | Because risk of CVD is considered worth it to reduce pain
92
renal syndrome side effects of NSAIDs due to decrease in PGE2
- increase Na+ retention - peripheral oedema - increase in blood pressure - increase in weight - congestive heart failure (rarely)
93
renal syndrome side effects of NSAIDs due to decrease in PGI2
- hyperkalaemia | - acute renal failure
94
‘Prostaglandin replacement therapy’/use of synthetic, selective analogues
Arthrotec = diclofenac + misoprostol (NSAID + reduced stomach acid) Diclofenac: NSAID Misoprostol: EP1/3 agonist, which restores cytoprotection; prevents stomach ulcers
95
Arthrotec is?
Diclofenac + misoprostol | NSAID + reduced stomach acid
96
What is Diclofenac?
NSAID
97
What is Misoprostol?
EP1/EP3 agonist, which restures cytoprotection and prevents stomach ulcers
98
PGE2 can lead to carcinogenesis, | how?
cAMP and calcium concentration induce: 1) direct targeting of gene transcription, inducing cell proliferation (growth) and migration (potential metastasis) 2) --> HIF-1alpha causes VEF transcription and angiogenesis 3) Production of Survivin which inhibits apoptosis 4) ---> MMPs --> increase invasiveness 5) --> PKA and PKC-->MAPK---1)
99
How do prostacyclins reduce intra-ocular pressure in glaucoma?
Reduce intra-ocular pressure relieving the optic nerve; allow fluid to drain freely Latanoprost – PGF2a analogue Bimatoprost – PGF2a analogue
100
Additional therapeutic uses for PGE analogues
``` Adjuncts to mifepristone and other agents used to terminate pregnancy Cervical ripening Potential uses to manage: Preterm labour Dysmenorrhoea Airway disease ```
101
What are the stimuli which induce AA production from phospholipid A?
cPLA2 | sPLA2
102
PGH2 and PGH3 make...
``` L-PGDS H-PGDS mPEGS-1 PGFS PGIS TXAS ```
103
L-PGDS and H-PGDS make what PG?
PGD2
104
mPEGS-1 makes what PG?
PGE2
105
PGFS makes what PG?
PGF2alpha
106
PGIS makes what PG?
PGI2
107
TXAS makes what?
TXA2