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.
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.
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.
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:
Those 9 acetyl-CoAs can continue into the citric acid cycle, where they can produce:
The products of the complete oxidation of a fatty acid are shown below.
Adding up the NADH and FADH2, the electron transport chain ATP production from beta-oxidation and the citric acid cycle looks like this:
8 (beta-oxidation) + 27 (TCA) = 35 NADH X 2.5 ATP/NADH = 87.5 ATP
8 (beta-oxidation) + 9 (TCA) = 17 FADH2 X 1.5 ATP/FADH2 = 25.5 ATP
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
4. Berg JM, Tymoczko JL, Stryer L. (2002) Biochemistry. New York, NY: W.H. Freeman and Company.
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