FATTY ACID SYNTHESIS

FATTY ACID SYNTHESIS

Important features of this pathway:
1) Synthesis takes place in cytosol; ?-oxidation takes place in mitochondrial matrix.
2) Intermediates are bound to sulfhydral groups of acyl carrier protein (ACP); intermediates of??-oxidation are bonded to CoA
3) Growing fatty acid chain is elongated by sequential addition of two-carbon units derived from acetyl CoA
4) Reducing power comes from NADPH; oxidants in ?-oxidation are NAD+ and FAD
5) Elongation of fatty acid stops when palmitate (C16) is formed; further elongation and insertion of double bonds carried out later by other enzymes



Fatty acid synthesis takes place in three stages:
1) Mitochondrial acetyl CoA is transported into cytosol via citrate transport system
Acetyl CoA is condensed with oxaloacetate to form citrate ---> antiported out with inward movement of anion
Citrate cleaved by cytosolic citrate lyase --> oxaloacetate + acetyl CoA
2) Formation of malonyl CoA
Acetyl CoA carboxylase is key regulatory enzyme
Influenced by glucagon --> inactivates enzyme in liver
Epinephrine inactivates enzyme in adipocytes
Citrate allosterically activates enzyme
Fatty acyl CoA allosterically inhibits enzyme