Primary tissues for fatty acid synthesis
Liver*, kidney, brain, lung, mammary glands, adipose
Where does fatty acid sythesis occur in the cell?
What are fatty acids synthesised from?
What is the main source of acetyl-CoA?
Major enzymes in fatty acid synthesis
Acetyl-CoA carboxylase, Fatty Acid synthase
From what is citrate formed?
Acetyl-CoA and OAA
Cleaves citrate into Acetyl-CoA and OAA. Is only found in the cytosol.
How is pyruvate formed from OAA in the cytosol?
Cytosolic malate DH forms malate, malic Ez forms pyruvate from malate
Formation of Malonyl CoA
Acetyl CoA carboxylase uses CO2 and ATP to make Acetyl CoA into Malonyl CoA
What activates acetyl CoA carboxylase?
Insulin (activates protein phosphatase)
What stimulates AMPK?
AMP, AMPK covalant (via Glucagon or Epi). Inhibits aceytl-CoA Carboxylase
Long-term “adative” regulation
Long high calories=increased synthesis of Acetyl CoA Carboxylase. Long low calorie=decreased synthesis of acetyl CoA carboxylase
What are the starting and ending units of fatty acid synthase?
acetyl-CoA starts, 2 carbons added at a time, product is palmitate
Adds acetyl group on #1 monomer
Adds malonyl group on monomer #2
Makes a 3-ketoacyl, causes decarboxylation, passes carbons from one monor to the other (back and forth)
Reduces 3 ketoacyl to 2 hydroxy using NADPH
Removes H2O to form a 2-enyol group
Saturates the CC double bonem uses NADPH, leaves a saturated acyl
Breaks off acyl group to leave palmitate
converts palmitate to palmitoyl-CoA to allow further reactions
What is a major source of NADPH?
pentose phosphate pathway
Where does fatty acid elongation take place?
What are the preferred substrates and products of fatty acid elongation?
Palmitoyl-CoA is substrate. Product is stearoyl-CoA (18C)
Why is elongation a separate process fron synthesis?
There are different enzymes doing the same process
Formation of monosaturated fatty acids
in the ER. Stearoyl-CoA desaturase. Desaturation always occurs at C9. Product is oleoyl CoA* or palmitoleoyl-CoA (stearoyl is preferred).
Functions of polyunsaturated fatty acids
increases membrane fluidity, source of eicosanoids
What carbons can humans desaturate?
4,5,6, and 9. CANNOT desaturate Beyond* C9
What are omega fatty acids?
Fatty acids counted from the furthest C, instead of the alpha carbon
Why are omega 3 and 6 necessary for dietary intake?
Cannot synthesize past C9, so must be taken in via diet