elongation, desaturation of fatty acids and formation of active molecules

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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