ELONGATION, DESATURATION of FATTY ACIDS The Department of Biochemistry of Medical Faculty Presents now ELONGATION, DESATURATION of FATTY ACIDS and FORMATION of ACTIVE MOLECULES Edited by Attila Sandor

Mechanism of fatty acid elongation in animal cells CH3-(CH2)14-CO-SCoA + OOC-CH2-CO-SCoA acyl-CoA malonyl-acyl-CoA CO2 Elongation system located in the ER HSCoA CH3-(CH2)14-CO-CH2-CO-SCoA 2 NADPH2 H2O Reduced to saturated C18 stearic acid via three basic ezymes of fatty acid synthesis Fatty acids are elongated on the head Elongation system acts on CoA esters rather than on ACP-esters Elongation system also uses malonyl-CoA as acceptor Authors`picture

Mechanism of fatty acid desaruration in animal cells O-O 4- Belongs to the “mixed- function oxidases”, that is, oxidases two substrate at the same time Acts on CoA esters in the ER togethe with the Cyt b5 reductase Intoduces duoble bonds before the 9th carbon atomin cis position Lehn.,4th ed. 21-13 p. 799

Action of plant desaturases The plant desaturases enzymes act on fatty 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

Formation of the most important fatty acids via combination of elongation and desaturation animals can put double bond only before the 9th C atom advantage of the w system: after elongation the numbering does not turn upside down w 6,9,12 w 6,9,12 w 6,9,12,15 Lehn.,4th ed. 21-12 p. 797

a 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, w 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. Steroids Lehn.,4th ed. 10-18 p. 358

Biologically active derivatives of arachidonic acid Anti-inflamatory drugs inhibit: Prostaglandins Steroids: Prostaglandins Tromboxans Leukotriens Non-steroids: Prostaglandins Tromboxans Steroids Aspirin Tromboxans Cyclooxygenase COX I,II Lipoxygenase Leukotriens Unknown author

Non-steroids (aspirin) inhibit: Lehn.,4th ed. p. 888 Steroids Steroids inhibit: Prostaglandins Tromboxans Leukotriens Non-steroids (aspirin) inhibit: Tromboxans Prostaglandins Non-steroids (aspirin) lipoxygenase Cyclooxygenane (COX I,II

Mechanism of action of non-steroid (e.g.aspirin) anti-inflamatory drugs

Lehn.,4th ed. 21-15/b p. 801

Structure of Phosphatidic acid Lehn.,4th ed.10-8 p. 350

Lehn.,4th ed.10-8 p. 350

Phosphatidylinositol 4,5 bisphosphate, Two major roles of inositol-phosphates as second messengers Spliting by phospholipase C Phosphatidylinositol 4,5 bisphosphate, PIP2 Phosphatidyl-inositol 3 kinase P I 3 K (enzyme) Diacyl-glycerol, DAG Inositol 1,4,5, triphosphate IP3 Phosphatidyl-inositol 3,4,5 trisphosphate, PIP3 Author`s picture

Actions of IP3 and DAG Lehn.,4th ed. 12-19, p. 443

PIP3 mediating the intracellular actions of insulin Author`s picture IRS=insulin receptor substrate; GSK3=glycogen synthase kinase 3; PKB/Akt= protein kinase B; GS= Glycogen synthase;

THANK YOU FOR YOUR ATTENTION The honored audience has the opportunity now to download the pictures of this lecture from here or from the intranet ActiveMoleculesfromFatty Acids.ppt Attila Sandor