Question

Under what nutritional conditions is fatty acid synthesis likely to occur? Discuss the roles of acetyl CoA and malonyl CoA in the synthesis of fatty acids

Answer 1

Under nutrient-replete conditions, the primary fuel of the liver is glucose rather than fat. Fatty acids are not subjected to β-oxidation and instead are incorporated into triglycerides for storage in lipid droplets or secretion in very low-density lipoproteins (VLDL). Dietary fat in the form of chylomicron remnants is taken up by the liver; de novo synthesis of fatty acids by FAS may make a modest contribution to storing energy as fat when nutrients are present in excess.

Fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases. This process takes place in the cytoplasm of the cell. Most of the acetyl-CoA which is converted into fatty acids is derived from carbohydrates via the glycolytic pathway. The glycolytic pathway also provides the glycerol with which three fatty acids can combine (by means of ester bonds) to form triglycerides (also known as "triacylglycerols" – to distinguish them from fatty "acids" – or simply as "fat"), the final product of the lipogenic process. When only two fatty acids combine with glycerol and the third alcohol group is phosphorylated with a group such as phosphatidylcholine, a phospholipid is formed.

synthesis of fatty acid:

(a)	Acetyl CoA:ACP transacylase		Activates acetyl CoA for reaction with malonyl-ACP
(b)	Malonyl CoA:ACP transacylase		Activates malonyl CoA for reaction with acetyl-ACP

Acetyl CoA carboxylase plays an essential role in regulating fatty acid synthesis and degradation. Recall that this enzyme catalyzes the committed step in fatty acid synthesis: the production of malonyl CoA (the activated two-carbon donor). Thus, this important enzyme is subject to both global and local regulation.

explanation:

The pyruvate produced by glycolysis is an important intermediary in the conversion of carbohydrates into fatty acids and cholesterol. This occurs via the conversion of pyruvate into acetyl-CoA in the mitochondrion. However, this acetyl CoA needs to be transported into cytosol where the synthesis of fatty acids and cholesterol occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA, citrate (produced by the condensation of acetyl CoA with oxaloacetate) is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the cytosol. There it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate can be used for gluconeogenesis (in the liver), or it can be returned into mitochondrion as malate. The cytosolic acetyl-CoA is carboxylated by acetyl CoA carboxylase into malonyl CoA, the first committed step in the synthesis of fatty acids