SUMMARY

• 27.1 Fatty Acids Are Processed in Three Stages

  Triacylglycerols can be mobilized by the hydrolytic action of lipases that are under hormonal control. Glucagon and epinephrine stimulate triacylglycerol breakdown by activating the lipases. Insulin, in contrast, inhibits lipolysis. Fatty acids are activated to acyl CoAs, transported across the inner mitochondrial membrane by carnitine, and degraded in the mitochondrial matrix by a recurring sequence of four reactions: oxidation by FAD, hydration, oxidation by NAD⁺, and thiolysis by coenzyme A. The FADH₂ and NADH formed in the oxidation steps transfer their electrons to O₂ by means of the respiratory chain, whereas the acetyl CoA formed in the thiolysis step normally enters the citric acid cycle by condensing with oxaloacetate. Mammals are unable to convert fatty acids into glucose because they lack a pathway for the net production of oxaloacetate, pyruvate, or other gluconeogenic intermediates from acetyl CoA.

• 27.2 The Degradation of Unsaturated and Odd-Chain Fatty Acids Requires Additional Steps

  Fatty acids that contain double bonds or odd numbers of carbon atoms require ancillary steps to be degraded. An isomerase and a reductase are required for the oxidation of unsaturated fatty acids, whereas propionyl CoA derived from chains with odd numbers of carbon atoms requires a vitamin B₁₂-dependent enzyme to be converted into succinyl CoA.

• 27.3 Ketone Bodies Are Another Fuel Source Derived from Fats

  The primary ketone bodies—acetoacetate and d-3-hydroxybutyrate—are formed in the liver by the condensation of acetyl CoA units. Ketone bodies are released into the blood and are an important fuel source for a number of tissues. After their uptake, ketone bodies are converted into acetyl CoA and processed by the citric acid cycle.

• 27.4 Metabolism in Context: Fatty Acid Metabolism Is a Source of Insight into Various Physiological States

  Diabetes is characterized by the inability of cells to take up glucose. The lack of glucose as a fuel results in a greater demand for fats as a fuel. Ketone bodies may be produced in such excess as to acidify the blood, a potentially lethal condition called diabetic ketosis. Ketone bodies are also an especially important source of fuel for the brain when glucose is limited, as in prolonged fasting.