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 to make pyruvate which can enter the TCA cycle to make energy. 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 oxygen to FAD (hence oxidation) to FAD to form trans-Enoyl CoA and FADH2. FADH2 is used 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 (hence, oxidation) to NADH to produce beta-Ketoacyl CoA and NADH + H+. NAHD is used 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 acetyl CoA. 

The above steps then repeat with each cycle ending with fatty acyl CoA with two less carbons, and a molecule of acetyl-CoA. The cycle continues until all the carbons on the fatty acyl CoA is cleaved. Hence, here is what the proces would look like if we stated with Capric acid (C10).

Summary of Steps

Energy Yield 

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. 


Beta-Oxidation is ramped up in times of starvation when adequate glucose is not available or if the diet is very low in carbohydrates. Since pyruvate (which comes from glucose) is used to make oxaloacetate, there won’t be enough of this molecule to react with acetyl CoA and enter the TCA cycle. This will therefore lead to a buildup of acetyl CoA. This accumulation will cause the production of energy via an alternate pathway called ketogenesis. In this process, acetyl CoA is converted to acetoacetate in the mitochondria of the liver. Acetoacetate then diffuses into the blood and taken to muscle cells to produce 3-hyroxybutyrate, a ketone body that can yield NADH for the electron transport chain. Acetone is also made but does not contribute to energy. It can escape the body through the breath, which by the way gives you bad breath. Since ketones are acidic in nature, excess may cause a drop in blood pH called ketoacidosis which can be fatal.

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

Courtney Simons
Courtney Simons is a food science professor. He holds a BS degree in food science and a Ph.D. in cereal science from North Dakota State University.
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