Week 6 Ecosinoids- Skildum Flashcards
Why do we need Arachidonic acid or linoleate from out diet?
We can’t unsaturate bonds so close to the omega carbon
How is A.A. stored?
As a membrane phospholipid (PIP2)
How is A.A. released from membrane phospholipid PIP2?
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
What do hydroxycortisone, prednisone and dexamethasone (cortiocsteroids) inhbit?
phospholipase A2
and cyclooygenases
What does A.A. produce using the cyclic pathway? What enzymes are involved?
cyclooxygenase and peroxidase makes PGH2,
PGI synthase makes prostaglandins from PGH2
TXA synthase makes throboxanes from PGH2
What does A.A. produce using the linear pathway? What enzymes are involved?
lipoxygenase makes 5-HPETE to 5-HETE which is converted to epoxide and reduced to make Leukotrienes (released by mast cells, and causes bronchoconstriction)
What is a sign of oxidative stress?
isoprostanes produced from membrane lipids under oxidative stress
what do monetlukast and zafirlukast do?
block leukotriene receptor, long term treatment of asthma
What does PGI2 do?
secreted by vascular endothelium
stops clotting, prevents platelet aggregation, promotes relaxation of smooth muscle and vasodialation (normal physiology)
What does TXA2 do?
promotes clotting
secreted by platelets
paracrine/ autocrine
supports platelet aggregation
Normal physiology ecosinoids?
PGI2, PGE2, PGD2
How do you make an anandamide?
add A.A. to ethanolamine head group
Where does Anadamides bind and what do they do?
Binds to CBI, CB2, TRPVI
They stop overporduction of cytokines, reduce inflammatory response
Where does PLC and PLD cleave in respect to the phosphate?
PLD - phosphate stays with glycerol
PLC- phosphate stays with head group
COX1 and COX2
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)
Aspirin, Naproxen, Acetaminopen, ibuprofen
non-specific inhibitors of COX1 and COX2
Aspirin- suicide inhibitory, covalently bonds COX1 and COX2, decreases Vmax
Others are competitive inhibitors
alpha-lactalbumin
upregulated after giving birth, changes specificity of galactosyltransferase to attach galactose to glucose to make lactose
Jaundice
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
Mannose 6- phosphate
tag put on hydrolytic proteins in golgi to be sent to lysosome, in lysosome lower pH dissociates enzyme from its receptor
lysosomal storage disease
defects in enzymes that degrade glycolipids (can only be digested in lysosome)
Tay-Sachs disease
early onset retardation defective gene in alphas subunit of hexosaminidase (only A defective) autosomal recessive most die by age three
Sandhoff disease
similar to tay-sachs, earlier onset, defect in B subunit of hexosaminidase (both A and B defective)
