Eicosanoids & Lipid Mediators: Prostaglandins, Thromboxane, Leukotrienes

Question 1

COX

Answer 1

cyclooxygenase enzyme (COX-1 and COX-2), contains iron, needs O2 co-factor, converts AA –> PGH2

Question 2

NSAID

Answer 2

non-steroidal anti-inflammatory drug

Question 3

PUFA

Answer 3

polyunsaturated fatty acid

Question 4

Eicosanoids

Answer 4

Lipid mediators derived from 20 carbon PUFA, includes prostaglandins, thromboxane, leukotrienes

Eicosanoids are autacoid mediators

Question 5

Omega 6 PUFA

Answer 5

arachidonic acid –> 2-series prostaglandins & thromboxane

Question 6

Omega 3 PUFA

Answer 6

EPA (eicosapentanoic acid) –> 3-series prostaglandins & thromboxane

Question 7

ARACHIDONIC ACID

Answer 7

REMEMBER ARACHIDONIC ACID – is the substrate for COX

Question 8

Eicosanoid Biosynthesis

Answer 8

1. Arachidonic acid is liberated from the PM following a stimulus
2. COX enzymes transform AA into PGs or Tx
3. PGs exit cells and bind to receptors to transmit signals to cells

Question 9

Arachidonic Acid Cascade

Answer 9

1. Phospholipase A2 releases AA
2. COX converts AA to PGH2
3. Tissue Isomerases convert PGH2 to PGD, PGE, PGF, PGI and TxA2
4. PG dehydrogenase or hydrolysis

Question 10

COX

Answer 10

Cyclooxygenase enzyme contains iron and requires O2 co-factor to convert AA to PGH2

Question 11

Eicosanoids are made, not stored

Answer 11

Is not a form of paracrine signaling (hormones, steroids)

Question 12

PG, Tx synthesis acts only after a stimuli activates phospholipase A2

Answer 12

Phospholipase A2 induces AA to come out of PM

Question 13

Limiting reagents of PG/Tx synthesis

Answer 13

O2 and AA, auto-inactivation of COX enzyme, metabolic degradation of PGs and spontaneous hydrolysis of Tx and PGI2

Question 14

Can find COX in all cells except

Answer 14

RBC

Question 15

Eicosanoids mediate autocrine and paracrine signaling nearby the cells that make them.

Answer 15

Unlike hormones, autacoids are short-lived. PGDH limits their accumulation and circulation via the blood stream.

Question 16

Autocrine signaling

Answer 16

Cell can make PGs/Tx and respond to PGs/Tx binding to receptor

Question 17

Paracrine signaling

Answer 17

Cell B lacks enzymes to make PGs or Tx, responds to PG/Tx made from cell A

Question 18

Not every cell can make every prostaglandin

Answer 18

Not every cell has every membrane receptor

Question 19

Prostaglandin and Thromboxane Receptors are G-proteins (7 layer)

Answer 19

Gs and Gq stimulatory G-proteins

Gs associated with AC (adenyl cyclase –> cAMP)
Gq associated with PLC (phospholipase C –> DAG/IP3 –> Ca2+)

Question 20

PGE2 (EP) and PGI2( IP) associate with Gs and AC

Answer 20

PGF2 (FP) and TxA2 (TP) associate with Gq and PLC

Question 21

Receptors: EP2, EP4 and IP

Answer 21

RELAX smooth muscles

Question 22

Receptors: FP and TP

Answer 22

CONSTRICT smooth muscles

Question 23

Phospholipase A2 (PLA2)

Answer 23

Liberate AA (arachidonic acid) from phospholipids

Question 24

Phospholipase C (PLC)

Answer 24

Liberates IP3 & DAG from phospholipids (PIP2)

Question 25

PGI2 name

Answer 25

Prostacyclin

Question 26

Important to have balance in constricting and relaxing eicosanoids

Answer 26

Or else you can have effects like angina pectoris

Question 27

COX-1 vs COX-2

Answer 27

COX-1 is constitutive (always expressed) COX-2 is inducible

Question 28

COX-1 functions

Answer 28

Responds to physiological stimuli to regulate physiological functions of PGs and Tx Has role in gut, repro and development

Question 29

NSAIDS cause a decrease in PG

Answer 29

Overuse of NSAID can cause gastric ulcer

Question 30

PGE2 in gut

Answer 30

Too little = gastric ulcer | Too much = diarrhea

Question 31

PGs in repro

Answer 31

Too little = delayed birth | Too much = pre-mature labor, birth

Question 32

PGs in development

Answer 32

PG keeps ductus arteriosus patent in fetus, NSAIDs help close it At birth, PGE2 is removed, ductus arteriosus closes

Question 33

COX-2 exception

Answer 33

COX-2 is normally expressed and plays a prominent role in kidney physiology

Question 34

COX-2 expression

Answer 34

Prominent role responding to pathological stimuli (inflammation, cancer)

Question 35

COX-2 in kidney

Answer 35

Deficit of PGs in kidney leads to Na/H2O retention (edema) and hypertension

Question 36

Cardinal signs of inflammation

Answer 36

1. Vasodilation, decreased platelet aggregation 2. Increased permeability 3. Increased temperature 4. Increased sensitivity to pain Redness, swelling, pain

Question 37

COX-1 and COX-2, PGs and inflammation

Answer 37

1. Inflammation stimulates AA release 2. COX-1 converts AA into PGE2 (increases) 3. PGE2 causes redness, swelling, pain Induced COX-2 follows same pathway and AMPLIFIES symptoms

Question 38

Platelets

Answer 38

1. No nucleus 2. Generate TxA2 (thromboxane) 3. Constrict blood vessels and amplify platelet aggregation

Question 39

Endothelium

Answer 39

1. Cells that line blood vessels 2. Make PGI2 (prostacyclin) 3. Relaxes blood vessels and inhibits platelet aggregation

Question 40

How does body regulate ratios of PGs and Tx?

Answer 40

By varying the levels of isomerases/synthases among different tissues Different cells can make different eicosanoids

Question 41

Hemostasis

Answer 41

Maintaining blood flow

Question 42

Collagen stimulates TxA2 formation by platelets

Answer 42

Clotting mechanism, reaction to severed blood vessels

Question 43

Platelet aggregation pathway

Answer 43

PLA2 activation --> AA --> COX-1 --> PGH2 --> TxA2 --> TP receptors --> signal transduction

Question 44

PGI2 and TxA2 work in concert with each other

Answer 44

Prevent systemic effect, when TxA2 is in action, PGI2 is working downstream of it

Question 45

COX-2 can be induced by endothelial cells

Answer 45

COX-2 induction may amplify PGI2 synthesis

Question 46

COX-2 cannot be induced by platelets

Answer 46

No nucleus, no de novo transcription of proteins (unlike endothelial cells)

Question 47

Arachidonic Acid rich in beef, EPA rich in fish

Answer 47

EPA --> TxA3 which is a weak vasoconstrictor, weak platelet aggregation Omega-3 PUFA reduce inflammatory processes, vasoconstriction, platelet aggregation

Question 48

Leukotrienes made from same pathway, substitute COX for 5-LOX (lipoxygenase)

Answer 48

Leukotrienes named because they are made by leukocytes and have a conjugated triene in structure

Question 49

Leukotriene A4 = LTA4

Answer 49

No receptor

Question 50

Leukotriene B4 = LTB4

Answer 50

BLT1,2 receptor

Question 51

Leukotriene C4 = LTC4

Answer 51

CysLT1, 2 receptor

Question 52

Leukotriene D4 = LTD4

Answer 52

CysLT1 receptor

Question 53

Leukotriene E4 = LTE4

Answer 53

CysLT receptor

Question 54

TEST ADVICE

Answer 54

Leukotrienes are always an incorrect test question answer