Beta-Oxidation

So far you have learned that following digestion of fatty acids, they are packaged in the form of triglycerides and transported to cells via chylomicrons or stored in adipose (fat) cells until they are ready for use. From chylomicrons or adipose tissue, triglycerides are broken down by lipase enzymes by a process called lipolysis to release glycerol and 3 fatty acids. Glycerol is then transported to the liver where it enters the glycolytic and gluconeogenic pathways. The fatty acids are taken to the cytosol of body cells to be converted to energy.

The fatty acids first enters the cytosol of the cell where they are activated by CoA to form fatty acyl CoA. This reaction requires an investment of ATP. Fatty acyl CoA then enters the inter-membrane space of the mitochondria via tiny pores in the outer mitochondria membrane called porins. It is then transported to the mitochondria matrix via the carnitine shuttle. 

The entire process of beta-oxidation involves 4 steps i.e. oxidation, hydration, oxidation, and cleavage.  

Step 1: Oxidation 

Fatty acyl CoA loses hydrogen to FAD (hence oxidation) to form trans-Enoyl CoA and FADH₂. FADH₂ is used in the electron transport chain to produce energy. 

Step 2: Hydration

Water is added to trans-Enoyl CoA to form 3-Hydroxyacyl CoA

Step 3: Oxidation

3-Hydroxyacyl CoA loses hydrogen to NAD⁺ (hence, oxidation) to produce beta-Ketoacyl CoA and NADH + H⁺. NADH is used in the electron transport chain to produced energy. 

Step 4: Cleavage (or thiolysis)

Beta-Ketoacyl CoA reacts with CoA to produce a fatty acyl CoA that is 2 carbons shorter than what was initially available in step 1, plus one acetyl CoA. 

The above steps then repeat with each cycle ending with fatty acyl CoA (n-2 carbon atoms), and a molecule of acetyl-CoA. The cycle continues until all the carbons on the fatty acyl CoA are cleaved and the final products are two acetyl CoA molecules.

Each cycle produces:

• 1 FADH₂ – Recall that each FADH₂ produces 1.5 ATP
• 1 NADH – Recall that each NADH produces 2.5 ATP
• 1 Acetyl CoA – – Recall that each FADH₂ produces 10 ATP

Problem: Calculate the number of ATP that can be obtained from palmitic acid (C16)

Solution

As you can see here, the amount of energy that you get from just one fat molecule is much more than what is possible from one molecule of glucose. That is why we get so much more calories from eating fat than from any other macromolecule. 

Reference: Timberlake, K. C. (2015). General, Organic, and Biological Chemistry: Structures of Life (5th ed.). San Francisco, CA: Pearson Education.