Fatty acids are synthesized from acetyl-CoA through seven chain elongation steps, increasing by two carbons each time, to produce a 16-carbon fatty acid called palmitic acid; most synthesized fatty acids are esterified into triglycerides for storage.
Fatty acids can be synthesized from the break down of carbohydrates into acetyl-CoA molecules. During glyoclysis, carbohydrates are converted into pyruvate, which is converted into acetyl-CoA in the mitochondrion. For fatty acid anabolism from this acetyl-CoA, it must first move out of the mitochondria into the cytoplasm. It cannot move out of the mitochondrion directly, so it is instead first converted to citrate in the citric acid cycle and transported in this form. The cytoplasmic enzyme ATP citrate lyase then converts citrate back into its constituent parts, acetyl-CoA and oxaloacetate (which returns to the mitochondrion). The cytoplasmic acetyl-CoA is then carboxylated to malonyl-CoA (three carbons) in an enzymatic reaction. The fatty acid synthase, a multienzyme complex that mediates chain elongation, then uses malonyl-CoA as a substrate and combines it with another acetyl-CoA molecule to form a 4-carbon fatty acid (one carbon is given off as CO₂). The addition of two carbons is repeated through a similar process seven times to produce a 16-carbon fatty acid called palmitic acid (palmitate). This process must occur in the presence of NADPH, which acts as a reducing agent. The palmitic acid can then be further processed, such as through esterification. Most fatty acids synthesized in this way will be esterified into triglycerides for storage.
MCAT Official Prep (AAMC)
Practice Exam 4 B/B Section Passage 2 Question 7
• Anabolism (synthesis) of fatty acids begins with acetyl-CoA, derived from the break down of carbohydrates in glycolysis.
• Acetyl-CoA is transported to the cytoplasm from the mitochondrion in the form of citrate.
• In the cytoplasm, acetyl-CoA is converted to malonyl-CoA.
• Malonyl-CoA is then used as the starting product for fatty acid synthase to carry out seven steps of carbon chain elongation to produce a 16-carbon fatty acid.
• Most synthesized fatty acids are esterified into triglycerides for storage.
Fatty acids: Lipids that contain a carboxylic acid functional group attached to a long-chain hydrocarbon tail.
Acetyl-CoA: A molecule that is involved in protein, carbohydrate and lipid metabolism by delivering an acetyl group to the citric acid cycle, which will be oxidized for energy production.
Palmitic acid: A common saturated fatty acid with the formula CH₃(CH₂)₁₄COOH that is the product of fatty synthesis.
Esterification: Any reaction (typically between an acid and an alcohol) that results in the production of an ester.
Triglycerides: A molecule made from a glycerol and three fatty acid chains; the main component of body fat.
Pyruvate: The conjugate base of pyruvic acid, the simplest alpha-keto acid, which contains a carboxylic acid and a ketone group; an important intermediate in metabolism.
Anabolism: The synthesis of complex molecules in living organisms from simpler ones together with the storage of energy.
Citric acid cycle (Krebs cycle): A biochemical pathway used by aerobic organisms to release stored energy found in carbohydrates, fats, and proteins into ATP and carbon dioxide; this occurs through the oxidation of acetyl-CoA.
Malonyl-CoA: The starting product for fatty acid synthesis, made from carboxylation of acetyl-CoA.
Fatty acid synthase: A large multienzyme complex that synthesizes palmitic acid (palmitate) from acetyl-CoA, malonyl-CoA, and NADPH.