To prepare for the MCAT, it's important to understand fatty acid oxidation, particularly the process known as beta-oxidation, which breaks down fatty acids into acetyl-CoA, a molecule that enters the TCA cycle for energy production. This process occurs in the mitochondrial matrix and requires oxygen.
Beta-oxidation begins with the activation of fatty acids. In this step, fatty acids are attached to coenzyme A (CoA), forming fatty acyl-CoA. Once activated, the fatty acid undergoes several reactions. First, dehydrogenation occurs, where two hydrogens are removed, resulting in the production of FADH₂ and the formation of a double bond between the alpha and beta carbons. Next, water is added in the hydration step, converting this double bond into a hydroxyl group. The hydroxyl group is then oxidized during the second dehydrogenation step, forming a carbonyl group and producing NADH. Finally, a thiolase enzyme cleaves off acetyl-CoA, which shortens the fatty acyl-CoA chain by two carbon atoms, repeating the cycle until the fatty acid is fully broken down.
Each cycle of beta-oxidation removes two carbon units, producing one acetyl-CoA, one FADH₂, and one NADH. However, if the fatty acid is unsaturated, additional steps and enzymes (such as enoyl-CoA isomerase and 2,4-dienoyl CoA) are required to handle the double bonds. The process is regulated by hormones, with glucagon stimulating fatty acid oxidation and insulin inhibiting it.
To give a specific example, the complete oxidation of a 16-carbon saturated fatty acid results in the production of 8 acetyl-CoA molecules, along with 7 NADH and 7 FADH₂ molecules. These products then enter the citric acid cycle and electron transport chain, where they contribute to ATP production.
Fatty acid oxidation plays a critical role during periods of fasting or low carbohydrate intake when glucose levels are insufficient. During these times, the liver can convert excess acetyl-CoA into ketone bodies, which serve as an alternative energy source. Understanding these processes will strengthen your knowledge of the biochemical principles that appear in the MCAT’s Biological and Biochemical Foundations of Living Systems section.