Fatty Acid Synthesis Flashcards
Where are fatty acids synthesized?
Cytoplasm
What is the first step in FA synthesis?
Moving Acetyl CoA to the cytoplasm for FA synthesis
How is acetyl CoA moved across the mitochondrial membrane to the cytosol?
Acetyl CoA is condensed with Oxaloacetate to form citrate, which is transported across the membrane.
What is the function of ATP-citrate lyase?
Breaks citrate down into acetyl CoA and oxaloacetate in the cytosol
Where is NADPH synthesized for the synthesis of palmitate?
8 molecules are formed when 8 acetyl CoA are transported to the cytoplasm
Remaining 6 come from pentose phosphate pathway
What is the rate limiting step for fatty acid synthesis?
Formation of malonyl CoA
Catalyzed by Acetyl CoA carboxylase
What is the active structure of Acetyl-CoA carboxylase?
Active enzyme exists as filaments, monomers are inactive
How is Acetyl CoA carboxylase regulated by phosphorylation?
Inactivated via phosphorylation by AMP-activated protein kinase
Activated by dephosphorylation by protein phosphatase 2A.
What triggers phosphorylation of acetyl-CoA carboxylase?
Glucagon and Epinephrine
How does citrate influence the activity of acetyl-CoA carboxylase?
Allosterically activates it by facilitating the polymerization of inactive dimers into active filaments
Phosphorylation reduces sensitivity to stimulating effect of citrate
What molecule counteracts the stimulatory effect of citrate?
Palmitoyl CoA
How does insulin affect fatty acid synthesis?
Stimulates synthesis by stimulating dephosphorylation of acetyl-CoA carboxylase
What is adaptive control of Fatty Acid synthesis?
Fasting then feeding will increase acetyl CoA carboxylase activity, increasing fatty acid synthesis
Describe the structure of Fatty Acid Synthase.
Two identical chains folded into 3 domains joined by flexible regions
7 catalytic sites
What is the function of acyl carrier protein?
Carries the intermediates during FA synthesis
How is fatty acid synthesis initialized?
Acetyl CoA bonds to FA synthase
Provides the omega carbon for the fatty acid chain
What provides the carbons for elongation of the fatty acid chain?
Malonyl CoA
How many NADPH and ATP are required for the synthesis of Palmitate?
14 NADPH
7 ATP
Where are the enzymes for elongation and desaturation of palmitate located?
Cytoplasmic face of the endoplasmic reticulum
What enzymes introduce double bonds to unsaturate fatty acids?
ER mixed function oxidases
Three membrane bound enzymes catalyze the introduction of double bonds.
2 molecules of water are released
What carbon is the limit for introducing double bonds in mammals?
Cannot desaturate beyond the delta-9 carbon
What are eicosanoids derived from?
20C polyunsaturated fatty acids
What are leukotrienes?
Derived from arachidonate, important in allergic reactions
What is the site of aspirin activity?
Prostaglandin synthase
What are 6 functions of prostaglandins?
Stimulate inflammation
Regulated blood flow to certain organs
Control ion transport
Modulate synaptic transmission
Induce sleep
Important in clotting
What are the sites of steroid action?
Phospholipase A2 - involved in synthesis of arachidonate
Cyclooxygenase activity of COX
What is the function of Thromboxane A2?
Promotes clotting smooth muscle contraction
What is the function of Prostacyclin (PGI2)?
inhibits platelet aggregation and promotes vasodilation
