To generate energy from fatty acids, they must be oxidized. This process occurs in the mitochondria, but long chain fatty acids cannot diffuse across the mitochondrial membrane (similar to absorption into the enterocyte). Carnitine, an amino acid-derived compound, helps shuttle long-chain fatty acids into the mitochondria. The structure of carnitine is shown below.

Figure 6.321 Carnitine shuttles fatty acids into the mitochondria^1,2

Fatty Acid Shuttling

As shown below, there are two enzymes involved in this process: carnitine palmitoyltransferase I (CPTI) and carnitine palmitoyltransferase II (CPTII). CPTI is located on the outer mitochondrial membrane, CPTII is located on the inner mitochondrial membrane. The fatty acid is first activated by addition of a CoA (forming acyl-CoA), then CPTI adds carnitine. Acyl-Carnitine is then transported into the mitochondrial matrix with the assistance of the enzyme translocase. In the matrix, CPTII removes carnitine from the activated fatty acid (acyl-CoA). Carnitine is recycled back into the cytosol to be used again, as shown in the figure and animation below.

Figure 6.322 Transfer of fatty acids into the mitochondria³

Fatty Acid Activation

As shown below, the first step of fatty acid oxidation is activation. A CoA molecule is added to the fatty acid to produce acyl-CoA, converting ATP to AMP in the process. Note that in this step, the ATP is converted to AMP, not ADP. Thus, activation uses the equivalent of 2 ATP molecules⁴.

Figure 6.323 Fatty Acid Oxidation

Fatty Acid Oxidation

Fatty acid oxidation is also referred to as beta-oxidation because 2 carbon units are cleaved off at the beta-carbon position (2nd carbon from the acid end) of an activated fatty acid. The cleaved 2 carbon unit forms acetyl-CoA and produces an activated fatty acid (acyl-CoA) with 2 fewer carbons, acetyl-CoA, NADH, and FADH2.

To completely oxidize the 18-carbon fatty acid above, 8 cycles of beta-oxidation have to occur. This will produce:

9 acetyl-CoAs

8 NADH

8 FADH2

Those 9 acetyl-CoAs can continue into the citric acid cycle, where they can produce:

9 GTP

9 FADH2

27 NADH

The products of the complete oxidation of a fatty acid are shown below.

Figure 6.324 Complete oxidation of a 18 carbon (C) fatty acid

Adding up the NADH and FADH2, the electron transport chain ATP production from beta-oxidation and the citric acid cycle looks like this:

NADH

8 (beta-oxidation) + 27 (TCA) = 35 NADH X 2.5 ATP/NADH = 87.5 ATP

FADH2

8 (beta-oxidation) + 9 (TCA) = 17 FADH2 X 1.5 ATP/FADH2 = 25.5 ATP

GTP

9 GTP = 9 ATP

Total ATP from complete oxidation of an 18 carbon fatty acid:

87.5 + 25.5 + 9 = 122 ATP

Subtract 2 ATP (ATP–>AMP) required for activation of the fatty acid:

122-2 = 120 Net ATP

Compared to glucose (32 ATP) you can see that there is far more energy stored in a fatty acid. This is because fatty acids are in a more reduced form and thus, they yield 9 kcal/g instead of 4 kcal/g like carbohydrates⁴.

The following animation reviews lipolysis and beta-oxidation.

References & Links

1. http://en.wikipedia.org/wiki/File:Carnitine_structure.png

2. https://simple.wikipedia.org/wiki/Mitochondria#/media/File:Animal_mitochondrion_diagram_en_(edit).svg

3.https://en.wikipedia.org/wiki/Carnitine_palmitoyltransferase_I#/media/File:Acyl-CoA_from_cytosol_to_the_mitochondrial_matrix.svg

4. Berg JM, Tymoczko JL, Stryer L. (2002) Biochemistry. New York, NY: W.H. Freeman and Company.

Links

Fatty acid transfer from cytoplasm to mitochondrian – http://brookscole.cengage.com/chemistry_d/templates/student_resources/shared_resources/animations/carnitine/carnitine1.html

Fatty Acid Metabolism – http://www.wiley.com/legacy/college/boyer/0470003790/animations/fatty_acid_metabolism/fatty_acid_metabolism.htm