Question

Draw a picture that shows FA oxidation vs. FA synthesis

• Color-code each pathway

Include:

• All steps to each pathway
• How they are Regulated by Insulin vs. Glucagon
• Indicate rate-limiting steps/enzymes
• ALL Enzymes, products and substrates
• Location of each pathway

Answer 1

fatty acid synthesis: Fatty acid synthesis occurs similarly to Beta-oxidation – acetyl groups are added to a growing chain, but the mechanism of the pathway is distinctly different from being simply the reverse of Beta-oxidation. The Synthesis mainly occurs in the cytosol (not mitochondria). It uses a moiety called Acyl-carrier protein (ACP) instead of CoA and the reducing agent NADPH (not NAD/FAD).

Acetyl-CoA is produced in two ways in the mitochondria –

• by Beta-oxidation of fatty acids, and

• by the combined action of pyruvate dehydrogenase (to decarboxylate pyruvate, producing acetate) and dihydrolipoyl transacetylase (to add the CoA to the acetate).

Under these conditions, acetyl-CoA is transported out of the mitochondrion to the cytosol where it can be used in fatty acid synthesis. This is accomplished using the tricarboxylate transport system in the inner mitochondrial membrane which pumps citrate out.

substrate for fatty acids synthesis is acetyl-CoA. and the product form from this pathway is palmitate a fatty acid. this pathway happened in cytosol.

rate limiting enzyme is acetyl-CoA carboxylase. all the enzyme required in fatty acid synthesis mentioned in figure.

Insulin stimulates the increased synthesis of acetyl-CoA carboxylase and fatty acid synthase (two critical enzymes for synthesizing fatty acids). thus promote fatty acid synthesis. opposite to insulin, glucagon is important for regulating lipid metabolism in part through its inhibition of fatty acid synthesis in adipocytes.

fatty acid oxidation:

Beta-oxidation of Fatty Acid

• Beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA.
• Acetyl-CoA enters the citric acid cycle while NADH and FADH2, which are co-enzymes, are used in the electron transport chain.
• It is referred as “beta oxidation” because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group.

substrates: free fatty acids, H2O.

products: one acetyl-CoA, one NADH, one FADH2 for every removal of a two-carbon group from the fatty acid chain.

The carnitine shuttle is a rate limiting step in the oxidation of fatty acids in the mitochondria and thus fatty acid oxidation can be regulated at this step.

Glucagon regulates lipolysis and fatty acid oxidation through inositol triphosphate receptor 1 in liver. glucagon increase fatty acid oxidation and promote production of acetyl-CoA. acetyl-CoA is used as substrate for glucose formation. Glucagon increases hepatic glucose production through stimulation of glycogenolysis and gluconeogenesis.