elongation, desaturation of fatty acids and formation of active molecules the department of...
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ELONGATION, DESATURATION of FATTY ACIDS
and FORMATION of ACTIVE MOLECULES
The Department of Biochemistryof Medical Faculty
Presents now
Edited by Attila Sandor
Mechanism of fatty acid elongation in animal cells
CH3-(CH2)14-CO-CH2-CO-SCoA
CO2
HSCoAElongation system located in the ER
Reduced to saturated C18 stearic acid via three basic ezymes of fatty acid synthesis
Fatty acids are elongated on the headElongation system acts on CoA esters rather than on ACP-estersElongation system also uses malonyl-CoA as acceptor
Authors`picture
CH3-(CH2)14-CO-SCoA + OOC-CH2-CO-SCoAacyl-CoA malonyl-acyl-CoA
2 NADPH2H2O
Mechanism of fatty acid desaruration in animal cells
Lehn.,4th ed. 21-13 p. 799
Belongs to the “mixed- function oxidases”, that is, oxidases two substrate at the same timeActs on CoA esters in the ER togethe with the Cyt b5 reductaseIntoduces duoble bonds before the 9th carbon atomin cis position
O-O
4-
Action of plant desaturases
The plant desaturases enzymes act onfatty acid chains in phosholipids rather than on CoA esters and introduce double bounds before and after the 9th carbon atom.
Lehn.,4th ed. 21-14 p. 800
animals can put double bond only before the 9th C atom advantage of the system: after elongation the numbering does not turn upside down
Formation of the most important fatty acids via combination of elongation and desaturation
6,9,12,15
6,9,12
6,9,12
Lehn.,4th ed. 21-12 p. 797
Strayer 3rd edition,20-19, p.490
CONCLUDING REMARKS
The overall equation of the synthesis of a palmitic acid :
7malonylCoA + 1AcCoA + 14 NADPH2 CH3-(CH2)14–COOH + 7 CO2 + 14NADP+ +6H2O + 8CoA
•The fatty acids are elongated at the head by C2 untits thus, the most fatty acids are even numbered.•The cytosolic fatty acid synthase enzyme synthetises only palmitic acid.•The longer and/or unsaturated fatty acids are formed by different microsomal enzymes•The odd-numbered fatty acids are synthtised when AT accepts proponyl-CoA by mistake
Spliting sites of phospholipases
Lehn.,4th ed.10-15 p. 355
Source of arachidonic acid
Arachidonic acid (20:4, 6,9,12,15) is the parenthal compound of many biologically active fatty acid derivatives. It is located in membrane phosholipids and released by phosholipase A2.
Lehn.,4th ed. 10-18 p. 358Steroids
Biologically active derivatives of arachidonic acid
Aspirin
COX I,II
Lipoxygenase
Cyclooxygenase
Non-steroids:
Leukotriens
ProstaglandinsTromboxans
Anti-inflamatory drugs inhibit:
Steroids
Prostaglandins
Tromboxans
Leukotriens
Steroids:
TromboxansProstaglandins
Unknown author
Steroids
Cycloo
xyge
nane (
COX I,II
Non-steroids (aspirin)inhibit:
Leukotriens
ProstaglandinsTromboxans
Steroids inhibit:
TromboxansProstaglandins
Non-steroids (aspirin)
lipoxygenase
Lehn.,4th ed. p. 888
Mechanism of action of non-steroid (e.g.aspirin) anti-inflamatory drugs
Lehn.,4th ed. 21-15/b p. 801
Lehn.,4th ed.10-8 p. 350
Structure of Phosphatidic acid
Lehn.,4th ed.10-8 p. 350
Two major roles of inositol-phosphates as second messengers
Phosphatidyl-inositol 3,4,5 trisphosphate,PIP3
Spliting by phospholipase C
Phosphatidyl-inositol 3 kinaseP I 3 K (enzyme)
Diacyl-glycerol, DAG
Inositol 1,4,5, triphosphateIP3
Phosphatidylinositol 4,5 bisphosphate,PIP2
Author`s picture
Actions of IP3 and DAG
Lehn.,4th ed. 12-19, p. 443
PIP3 mediating the intracellular actions of insulin
IRS=insulin receptor substrate; GSK3=glycogen synthase kinase 3;PKB/Akt= protein kinase B; GS= Glycogen synthase;
Author`spicture
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