Regulating Lipid Synthesis

Acetyl-CoA carboxylase is essential for fatty acid synthesis, it provides malonyl-CoA, necessary for production of palmitate, a fatty acid. The enzyme is regulated via phosphorylation and dephosphorylation. Insulin activates the enzyme by dephosphorylation. Glucagon and epinephrine deactivate on the other hand the enzyme by phosphorylation (adding a phosphate group to the molecule). Citrate activates the enzyme while palmitoyl-CoA, the end product of fatty acid synthesis, inhibits it.

In fatty acid synthesis, all of the enzymes listed are are regulated by insulin. Pyruvate dehydrogenase transforms pyruvate into acetyl-CoA. Glucokinase transforms glucose in glucose 6-phosphate. Acetyl-CoA carboxylase converts acetyl-CoA to malonyl-CoA. Fatty acid synthase converts malonyl-CoA to fatty acid palmitate. Insulin regulation is essential for proper utilization of dietary carbohydrates and lipids after meals.

Carnitine transports fatty acids from the cytosol to the mitochondria. Acetyl-CoA is converted to citrate as it exits the mitochondria and enters the cytosol.

The citrate shuttle moves acetyl-coenzyme A (CoA) from the mitochondria to the cytosol to make it available for fatty acid synthesis. The process involves multiple reactions and enzymes such as citrate lyase. Citrate acts as as a carrier agent for acetyl-CoA molecules from the mitochondria to the cytoplasm and in reverse. Oxaloacetate, a product of citrate lysis in the cytoplasm is not moved directly back in the mitochondria, but rather is converted back to malate and pyruvate.

The two carbons that remain after the addition of malonyl-CoA are added as an acetyl group with the carbonyl carbon on the interior of the chain, which is to say a ketone. Then, the carbonyl is reduced to form an alcohol. Next, the alcohol is dehydrated to form an alkene. Finally, the alkene is reduced to saturate the chain, forming an alkyl group.