Chapter 25: DNA Metabolism: Replication, Repair, and Recombination

Section 25.1 outlines the preparation of precursors, starting with the conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase (ACC)—the committed and highly regulated step in fatty acid synthesis. This reaction requires biotin and is activated by citrate and inhibited by palmitoyl-CoA and AMP-activated protein kinase (AMPK). Section 25.2 details the multienzyme complex fatty acid synthase (FAS), which catalyzes a repeating four-step cycle: condensation, reduction, dehydration, and a second reduction. These steps extend the growing fatty acid chain by two carbon units per cycle, using malonyl-CoA as the donor. The process results in the formation of palmitate (C16:0) after seven cycles, which may then undergo further elongation or desaturation. The ACP (acyl carrier protein) plays a central role in shuttling intermediates between catalytic domains. Section 25.3 explores the sources of NADPH required for fatty acid synthesis, primarily the pentose phosphate pathway and the malic enzyme reaction. The chapter also covers the elongation and desaturation of fatty acids in the endoplasmic reticulum, involving elongases and desaturases to produce unsaturated and longer-chain fatty acids, including essential ones like linoleate and linolenate, which must be obtained from the diet. Section 25.4 focuses on the regulation of fatty acid biosynthesis. Key regulatory mechanisms include allosteric control of acetyl-CoA carboxylase, hormonal regulation via insulin and glucagon, and transcriptional regulation of lipogenic enzymes in response to nutritional status. The chapter concludes with clinical relevance, including obesity, metabolic syndrome, and fatty liver disease, all of which involve dysregulation of lipid synthesis pathways. The integration of fatty acid biosynthesis with carbohydrate and energy metabolism is emphasized as essential for metabolic homeostasis.