Exam3Lec5EicosanoidMetabolism Flashcards
What are the clinical involvements of eicosanoids?
- Inflammation, arthritis, psoriasis
- pain and fever
- reproduction
- peptic ulcers
- kidney disease
- patency of the ductus arteriosus
- platelet aggregation and thrombosis
- alzheimers disease
- colon cancer
What are the members of the eicosanoid family?
- Prostaglandins
- Prostacyclins
- Thromboxanes
- Leukotriences
- Lipoxins
- Hydroxy & epoxy eicosaenoic acids
- levuglandins
What is the chemistry of eicosanoids?
basis is prostanoic acid which is 20 Carbons
What are the major prostaglandins?
PGE and PGFalpha
because they have been studied more
What are the minor prostaglandins?
PGA PGD
less studeis on these
What are the cyclic endo-peroxides prostaglandins?
PGG or PGH
intermediates in synthesis pathway of peroxides
What are the Prosta-cyclin prostaglandins
PGI
Is there a storage form of eicosanoids?
NO, they are not stored, they are synthesized on demand
What are the pre-cursors of eicosanoids?
poly unsaturated fatty acids
forms eicosanoids of that series
What are the three series of poly-unsaturated faty acids pre-cursors?
Series 1: 8,11,14-Eicosatrienoic acid
Series 2: Arachidonic acid
Series 3: Eicosapentaenoic acid
Can you use series one to get a series 3 fa acid?
No because what you start with is what you get
The type of fa we get is determeined by what?
fa precursoes
Release of arachidonic acid
The poly unsat fa is esterifed on which postion carbon?
Carbon 2 of phosphatidylinositol
Which enzyme cataylzes RLS in biosytheis of eicosanoids (add pic)
Phospholipase A2
cleaves polyunsat fa from postion 2 and forms lysophosphatidylinositol and free arachidonic acid. Free arachidonic is used to make eicasanoids
Once arachidonic acid is releases, what two pathways can it undergo?
Cyclooxygenase
and Lipoxygenasae
What 2 isozymes we have for clylooxygenasse?
Cox1: responsible for synthesizing eic for basal cellullar activity “ house-keeping enzyme+ needed to mainitain normal function of self
Cox2: inducible coxase for inflammatory response
cox 1 and 2 are used to make eic
What 2 isozymes we have for cyclooxygenasse?
Cox1: responsible for synthesizing eic for basal cellullar activity “ house-keeping enzyme+ needed to mainitain normal function of self
Cox2: inducible coxase for inflammatory response
cox 1 and 2 are used to make eic
Exists as a homodimer and has a functional heme grp that is required
cyclooxygenasse
repsonsible for making specific eic in a specic tissue
synthase (concentration of enzyme in tissue)
Cox 1 and 1 has how many enzymatic activities?
2 enzymatic activity on the same polypeptide chain.
1. cox activity
2. peroxidase activity
prostaglandins synthase is the same thing as what?
Cox pathway
(PGH2 synthase or cox1 or 2 and peroxidase)
Mechanism of aspirin inhibition of cyclooxygenase
Asprin is taken and is in the vicinity of active cox and cov modifies the serine residue attached and it becomes inactive cox with a modified serine residue
What explanins the medicinal efficacy of aspirin?
Asprin is the ONLY NSAID that can covalently modify the active site of cox (serine residue) this makes cox inactive.
Is cox 1 or 2 more sensitive to inhibition by aspirin?
Cox 1, cox 2 is less sensitive
