24.2 Oxidation of Fatty Acids A large amount of energy is obtained when fatty acids undergo oxidation in the mitochondria to acetyl CoA. beta oxidation, (β oxidation) which removes two-carbon segments containing the alpha and beta carbon from the carboxyl end of the fatty acid. Learning Goal Describe the metabolic pathway of β oxidation.

β Oxidation A cycle in β oxidation produces an acetyl CoA and a fatty acid that is shorter by two carbons. repeats until the original fatty acid is completely degraded to two-carbon units that form acetyl CoA, which enters the citric acid cycle.

Fatty Acid Activation Fatty acids in the cytosol are transported through the inner mitochondrial membrane to undergo β oxidation in the matrix. In an activation process, a fatty acid is combined with CoA to yield a high-energy fatty acyl CoA. energy is released by the hydrolysis of ATP to AMP and used to drive the reaction.

Transport of Fatty Acyl CoA A transport system called the carnitine shuttle carries fatty acids into the mitochondria from the cytosol. Carnitine acyltransferase catalyzes the transfer of a fatty acyl group to the hydroxyl group of carnitine to produce fatty acyl carnitine. Fatty acyl carnitine then passes through the inner mitochondrial membrane into the matrix.

Transport of Fatty Acyl CoA

Transport of Fatty Acyl CoA In the matrix, another carnitine acyltransferase catalyzes the reverse reaction that transfers the fatty acyl group to CoA to reform fatty acyl CoA. releases the carnitine and returns to the cytosol. Thus, the carnitine shuttle moves fatty acyl CoA from the cytosol into the matrix, where the fatty acid can undergo β oxidation.

Carnitine Shuttle System In the carnitine shuttle system, fatty acids are activated and transported from the cytosol through the inner mitochondrial membrane into the matrix.

Beta (β) Oxidation of Fatty Acids: Reaction 1 Fatty acyl CoA undergoes beta (β) oxidation in a cycle of four reactions. In reaction 1, acyl CoA dehydrogenase catalyzes the transfer of hydrogen atoms from the α and β carbons of the activated fatty acid. a trans C = C bond is formed between α and β carbons, and the reduced coenzyme FADH2 is produced.

Beta (β) Oxidation of Fatty Acids: Reaction 2 In reaction 2, a hydration reaction catalyzed by enoyl CoA hydratase adds the components of water to the trans double bond. a hydroxyl group (—OH) attaches to the β carbon of the fatty acid, and a hydrogen atom attaches to the α carbon.

Beta (β) Oxidation of Fatty Acids: Reaction 3 In reaction 3, the secondary hydroxyl group on the β carbon (carbon 3) is oxidized by 3-hydroxyacyl CoA dehydrogenase to yield a ketone. the hydrogen atoms removed in the oxidation are transferred to NAD+ to yield a β keto or 3-keto group and the reduced coenzyme NADH.

Beta (β) Oxidation of Fatty Acids: Reaction 4 In reaction 4, the Cα — Cβ bond is cleaved by β-ketoacyl CoA thiolase to yield a two-carbon acetyl CoA and a new fatty acyl CoA that is shortened by two carbon atoms. the shorter fatty acyl CoA repeats the four steps of the β- oxidation cycle until the original fatty acid is completely degraded to two-carbon units of acetyl CoA.

Fatty Acid Length Determines Cycle Repeats The number of carbons in a fatty acid determines the number of times the cycle repeats and the number of acetyl-CoA units it produces. The total number of times the cycle repeats is one fewer than the total number of acetyl groups it produces. Odd-numbered fatty acids go through the same four steps of β oxidation until the final cycle, in which the remaining fatty acyl CoA is cleaved to yield a propionyl CoA (C3) group and an acetyl CoA.

Beta (β) Oxidation of Fatty Acids Capric acid (C10) undergoes four oxidation cycles that repeat reactions 1 to 4 and yield five acetyl CoA molecules, four NADH, and four FADH2.

Oxidation of Unsaturated Fatty Acids Some fats from our diets contain unsaturated fatty acids, which have one or more cis double bonds. An isomerase converts a cis double bond to a trans double bond between the α and β carbons so the fatty acid can undergo hydration. It forms a product that enters β oxidation at reaction 2, so the energy released by the β oxidation of an unsaturated fatty acid is slightly less because no FADH2 is produced in that cycle.

Study Check Match the reactions of β oxidation with each of the following: Water is added. FADH2 forms. A two-carbon unit is removed. A hydroxyl group is oxidized. NADH forms. 1) oxidation 1 2) hydration 3) oxidation 2 4) acetyl CoA cleaved

Solution Match the reactions of β oxidation with each of the following: Water is added. 2) hydration FADH2 forms. 1) oxidation 1 A two-carbon unit is removed. 4) acetyl CoA cleaved A hydroxyl group is oxidized. 3) oxidation 2 NADH forms. 3) oxidation 2

Study Check How many acetyl CoA groups are produced by the complete β oxidation of palmitic acid (C16)? 1) 16 2) 8 3) 7 How many oxidation cycles are necessary to completely oxidize palmitic acid (C16)?

Solution How many acetyl CoA groups are produced by the complete β oxidation of palmitic acid (C16)? 2) 8 (16 C/2 = 8) How many oxidation cycles are necessary to completely oxidize palmitic acid (C16)? 3) 7 (16 C/2 – 1 = 7)