Fatty Acid Synthesis and Acetyl-CoA Transport

Acetyl-CoA Transport and Fatty Acid Synthesis

• In non-photosynthetic eukaryotes, acetyl-CoA is made in the mitochondria and transported into the cytosol for fatty acid synthesis at a cost of 2 ATPs.
• The total cost of fatty acid synthesis is 3 ATPs per 2C unit, which is approximately 50% of the NADPH+H+ units necessary for fatty acid biosynthesis.

Overview of Fatty Acid Synthesis

• Fatty acids are synthesized in several passes, with each pass involving the reduction of a carbonyl carbon to a methylene carbon.
• The acetate unit for fatty acid synthesis comes from activated malonate in the form of malonyl-CoA.

The Acetyl-CoA Carboxylase Reaction

• The acetyl-CoA carboxylase reaction is the committed step in fatty acid synthesis.

Fatty Acid Synthase (FAS)

• FAS I is a single polypeptide chain with 7 active sites in vertebrates, leading to a single product: palmitate (16:0).
• FAS II is a separate enzyme system in plants and bacteria, producing a variety of fatty acid products (saturated, unsaturated, branched, etc.).

Synthesis of Fat (Triacylglycerides) and Phospholipids

• Animals and plants store fat (triacylglycerides) for fuel.
• The typical 70-kg human has approximately 15 kg of fat, which can last for 12 weeks.
• Animals, plants, and bacteria make phospholipids for cell membranes.
• Both molecules contain a glycerol backbone and 2 (phospholipids) or 3 (triacylglycerides) fatty acids.

Synthesis of Backbone of TAGs and Phospholipids

• Most glycerol 3-phosphate comes from dihydroxyacetone phosphate (DHAP) via glycerol 3-phosphate dehydrogenase.
• Some glycerol 3-phosphate is made from glycerol via glycerol kinase (minor pathway in liver and kidney, absent in adipocytes).

Catabolism and Anabolism of Fatty Acids

• Catabolism of fatty acids produces acetyl-CoA and reducing power (NADH+H+, FADH2) in the mitochondria.
• Anabolism of fatty acids requires acetyl-CoA and malonyl-CoA, as well as reducing power from NADPH+H+, and occurs in the cytosol in animals and chloroplasts in plants.

Fatty Acid Biosynthesis - Place of Action

• Fatty acid synthesis takes place in the cytosol of every cell with mitochondria, although the rate differs between cells.

Fatty Acid Synthesis and NADPH+H+ Levels

• Fatty acid synthesis occurs in cell compartments where NADPH+H+ levels are high, such as in the cytosol of animals and yeast.
• Sources of NADPH+H+ include the pentose phosphate pathway and malic enzyme in adipocytes, and the pentose phosphate pathway in hepatocytes and mammary gland.