During long periods of starvation, after the liver and muscle glycogen stores have been depleted, the body must rely on lipolysis, the breakdown of triglycerides stored in adipose tissue, for energy production. Triglycerides are composed of a 3 carbon glycerol backbone with 3 chains of fatty acids attached, one to each carbon. During lipolysis, hormone sensitive lipase enters triglyceride stores in adipocytes and breaks the bonds between the glycerol backbone and the fatty acid chains, resulting in 1 glycerol molecule and 3 free fatty acids from each triglyceride.
The glycerol molecule is used during gluconeogenesis to form glucose, which then undergoes glycolysis before entering the Krebs cycle to produce ATP. The free fatty acids bind to albumin and travel via the blood to their designated cell, where the fatty acids diffuse through the cell membrane into the cytosol (Medeiros, 2012). In the cytosol, thiolase converts the fatty acids into fatty acyl-CoA which travels through the cytosol to the mitochondria. In order to cross the mitochondrial membrane, transferase converts the fatty acyl-CoA into acyl-carnitine which can diffuse through the membrane. Inside the mitochondria, transferase converts the acyl-carnitine back into fatty acyl-CoA which then undergoes beta-oxidation to form Acetyl-CoA and join the Krebs cycle. Beta oxidation is the repetitive process of cleaving 2 carbon molecules off the end of a fatty acid chain to form acetyl-CoA molecules. This process is repeated until all of the carbons have been cleaved into 2-carbon acetyl-CoA molecules, which produces 5 ATP molecules per cleavage. For example, arachidic acid, a 20-carbon fatty acid, would undergo 9 cleavages, producing 45 ATP molecules. The synthesis of the 2-carbon molecule into acetyl-CoA produces another 12 ATP molecules for each acetyl-CoA synthesized. Beta oxidation of arachadic acid produces 10 molecules for acetyl-CoA synthesis and 120 ATP molecules. Because 2 ATP units are lost during the conversion of fatty acid to fatty acyl-CoA, arachidic acid produces a total of 163 (45+120-2=163) ATP molecules during beta oxidation. Additionally, the 10 acetyl-CoA units can enter the Krebs cycle, synthesizing another 120 ATP molecules.
The conversion of fatty acyl-CoA into acetyl-CoA results in 3 by-products known collectively as ketone bodies. These by-products are acetoacetate, beta-hydroxybutyrate, and acetone. Ketone bodies are transported via the circulatory system and used by different tissues for energy production via the Krebs cycle (Medeiros, 2012). During times of starvation, when glycogen stores have been depleted, the brain can derive up to 50% of its energy from ketone bodies. Although ketones are used for energy production, overproduction of these molecules can lead to pH imbalances in the blood (Medeiros, 2012).
Medeiros, D.M. & Wildman, R.E.C.. (2012). Advanced Human Nutrition. Jones & Bartlett Publishers. ISBN: 9780763780395.