Chapter 24: Genes and Chromosomes: Chromatin Structure, Supercoiling, and Epigenetics

Genes and Chromosomes: Chromatin Structure, Supercoiling, and Epigenetics fatty acids bind to albumin for transport to energy-demanding tissues, while glycerol is converted to a glycolytic intermediate in the liver. Section 24.1 introduces the activation of fatty acids in the cytosol by acyl-CoA synthetase to form fatty acyl-CoA, which is then transported into the mitochondrial matrix via the carnitine shuttle—a process involving carnitine acyltransferase I and II. Inside the mitochondria, β-oxidation occurs in a cycle of four reactions: dehydrogenation (producing FADH₂), hydration, another dehydrogenation (producing NADH), and thiolytic cleavage by β-ketothiolase, which releases acetyl-CoA. Each round of β-oxidation shortens the fatty acid chain by two carbons, and the products—NADH, FADH₂, and acetyl-CoA—feed into the electron transport chain and the citric acid cycle to produce ATP. Section 24.2 explores the oxidation of unsaturated and odd-chain fatty acids, which require additional enzymes such as enoyl-CoA isomerase and 2,4-dienoyl-CoA reductase to process double bonds. Odd-chain fatty acids yield propionyl-CoA, which is converted to succinyl-CoA via a biotin- and vitamin B₁₂-dependent pathway. Section 24.3 focuses on ketone bodies—acetoacetate, β-hydroxybutyrate, and acetone—which are produced in the liver from excess acetyl-CoA during fasting or carbohydrate deprivation. These water-soluble molecules can be transported to other tissues, such as brain and muscle, where they are reconverted to acetyl-CoA for energy. The chapter concludes by highlighting the clinical relevance of lipid metabolism, including diabetic ketoacidosis, carnitine deficiency, and inherited β-oxidation disorders. It also emphasizes the high energy yield of fatty acid oxidation and the metabolic flexibility it offers under varying physiological conditions.