Week 6 Ecosinoids- Skildum

Question 1

Why do we need Arachidonic acid or linoleate from out diet?

Answer 1

We can’t unsaturate bonds so close to the omega carbon

Question 2

How is A.A. stored?

Answer 2

As a membrane phospholipid (PIP2)

Question 3

How is A.A. released from membrane phospholipid PIP2?

Answer 3

Phospholipase A2 can cleave it directly from PIP2

Phospholipase C cleaves into diacylglycerol and inisitol head group, diacylglycerol lipase cleaves into A.A. and monoacylglycerol

Question 4

What do hydroxycortisone, prednisone and dexamethasone (cortiocsteroids) inhbit?

Answer 4

phospholipase A2

and cyclooygenases

Question 5

What does A.A. produce using the cyclic pathway? What enzymes are involved?

Answer 5

cyclooxygenase and peroxidase makes PGH2,

PGI synthase makes prostaglandins from PGH2

TXA synthase makes throboxanes from PGH2

Question 6

What does A.A. produce using the linear pathway? What enzymes are involved?

Answer 6

lipoxygenase makes 5-HPETE to 5-HETE which is converted to epoxide and reduced to make Leukotrienes (released by mast cells, and causes bronchoconstriction)

Question 7

What is a sign of oxidative stress?

Answer 7

isoprostanes produced from membrane lipids under oxidative stress

Question 8

what do monetlukast and zafirlukast do?

Answer 8

block leukotriene receptor, long term treatment of asthma

Question 9

What does PGI2 do?

Answer 9

secreted by vascular endothelium
stops clotting, prevents platelet aggregation, promotes relaxation of smooth muscle and vasodialation (normal physiology)

Question 10

What does TXA2 do?

Answer 10

promotes clotting
secreted by platelets
paracrine/ autocrine
supports platelet aggregation

Question 11

Normal physiology ecosinoids?

Answer 11

PGI2, PGE2, PGD2

Question 12

How do you make an anandamide?

Answer 12

add A.A. to ethanolamine head group

Question 13

Where does Anadamides bind and what do they do?

Answer 13

Binds to CBI, CB2, TRPVI

They stop overporduction of cytokines, reduce inflammatory response

Question 14

Where does PLC and PLD cleave in respect to the phosphate?

Answer 14

PLD - phosphate stays with glycerol

PLC- phosphate stays with head group

Question 15

COX1 and COX2

Answer 15

COX1 makes prostaglandins involved in normal physiology (always on) (like stimulating stomach to secrete mucin to protect it from acidity)

COX2 on in response to cell damage and infection. Stimulates inflammatory prostaglandins (inflammation, pain, fever)

Question 16

Aspirin, Naproxen, Acetaminopen, ibuprofen

Answer 16

non-specific inhibitors of COX1 and COX2

Aspirin- suicide inhibitory, covalently bonds COX1 and COX2, decreases Vmax

Others are competitive inhibitors

Question 17

alpha-lactalbumin

Answer 17

upregulated after giving birth, changes specificity of galactosyltransferase to attach galactose to glucose to make lactose

Question 18

Jaundice

Answer 18

RBC broken down, need to get rid of heme

heme -> biliverdin(green) –> bilirubin (yellow)

bilirubin is not very soluble so transported in blood by albumin

in liver, bilirubin is glycosylated with glucuronates

it is then more soluble and can be excreted in bile or urine

*if heme degredation exceeds capacity to excrete it, bilirubin will diffuse out to blood and into tissues making you yellow

Question 19

Mannose 6- phosphate

Answer 19

tag put on hydrolytic proteins in golgi to be sent to lysosome, in lysosome lower pH dissociates enzyme from its receptor

Question 20

lysosomal storage disease

Answer 20

defects in enzymes that degrade glycolipids (can only be digested in lysosome)

Question 21

Tay-Sachs disease

Answer 21

early onset
retardation
defective gene in alphas subunit of hexosaminidase (only A defective)
autosomal recessive
most die by age three

Question 22

Sandhoff disease

Answer 22

similar to tay-sachs, earlier onset, defect in B subunit of hexosaminidase (both A and B defective)