ABSTRACT
Fatty acids, mostly as their activated coenzyme A esters, participate in many metabolic processes in human nerve and skeletal muscle (Figure 48.1). They are broken down, primarily in mitochondria and peroxisomes, to release electrons to be used to drive ATP synthesis, or to remove species (e.g., phytanic acid) with no biological function in humans. They are used for synthesis of complex lipids that are incorporated into membranes, or that are storage vehicles (triacylglycerols). Fatty acids
I. Introduction ........................................................................................................................ 1197 II. Fatty Acid Metabolism in Muscle and Nerve ........................................................................ 1198 A. Fatty Acid Metabolism in Peroxisomes ....................................................................... 1199 a. The Fatty Acid β-Oxidation Pathway in Peroxisomes ............................................ 1199 b. The Fatty Acid α-Oxidation Pathway ..................................................................... 1200 c. Synthesis of Ether Lipids ........................................................................................ 1200 B. β-Oxidation of Fatty Acids in Mitochondria ................................................................ 1202 C. Regulation of Fatty Acid Metabolism in Skeletal Muscle ........................................... 1204 III. Neuromuscular Disorders Associated with Fatty Acid Metabolism .................................. 1205 A. Peroxisomal Disorders ................................................................................................. 1205 a. Peroxisome Assembly Disorders ............................................................................ 1206 b. Disorders Associated with Single Enzyme De7 ciencies in Peroxisomes ............... 1206 B. Genetic Disorders of Mitochondrial Fatty Acid Oxidation .......................................... 1209 a. Disorders of the Carnitine Cycle ............................................................................. 1209 b. Disorders of the β-Oxidation Spiral and Electron Transfer to the Respiratory Chain .. 1211 C. Chanarin-Dorfman Disease ......................................................................................... 1213 D. Barth Syndrome ........................................................................................................... 1214 E. Diabetes and Obesity .................................................................................................... 1215 a. Diabetic Neuropathy ............................................................................................... 1215 b. Fatty Acids and Insulin Resistance in Skeletal Muscle ........................................... 1217 F. Nutritional De7 ciencies ............................................................................................... 1218 a. Protein-Energy Malnutrition ................................................................................... 1218 b. Anorexia Nervosa ................................................................................................... 1218 c. Myopathy, Wasting Syndrome, and Lipodystrophy Associated with
HIV Infection .......................................................................................................... 1218 IV. Summary ............................................................................................................................ 1219 References ................................................................................................................................. 1219
contribute to covalent modi7 cation of proteins (N-myristoylation and palmitoylation), and participate in regulation of enzymatic activities and other metabolic processes.
