Chapter 21: Lipid Biosynthesis: Fatty Acids, Membrane Phospholipids, Cholesterol, and Steroids

Section 21.1 opens with an overview of carbohydrate metabolism, tracing glucose uptake into cells and its conversion through the ten enzymatic steps of glycolysis. The pathway is divided into two phases: the investment phase, where ATP is consumed to phosphorylate glucose and fructose-6-phosphate, and the payoff phase, which yields ATP and NADH as glyceraldehyde-3-phosphate is converted to pyruvate. Key enzymes such as hexokinase, phosphofructokinase-1 (PFK-1), and pyruvate kinase are described in detail, with an emphasis on their regulatory roles. Allosteric control mechanisms and feedback inhibition (e.g., by ATP and citrate) are introduced to show how glycolysis is tightly coordinated with cellular energy needs. Section 21.2 introduces the hexose monophosphate pathway, which branches from glycolysis at glucose-6-phosphate. This pathway serves two major functions: producing NADPH for reductive biosynthesis (e.g., fatty acid synthesis) and generating ribose-5-phosphate for nucleotide synthesis. The oxidative phase involves glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the rate-limiting step and is regulated by NADP⁺/NADPH ratios. The non-oxidative phase involves a series of reversible sugar-phosphate interconversions, enabling the cell to balance NADPH and ribose-5-phosphate production depending on its metabolic needs. The chapter also explores how glycolysis and the pentose phosphate pathway integrate with other major pathways like gluconeogenesis and the TCA cycle. In addition, Section 21.3 discusses the importance of glycolysis in anaerobic conditions, such as in red blood cells or muscle under low oxygen, leading to lactate production via lactate dehydrogenase. The chapter concludes by emphasizing the metabolic flexibility of these pathways in various tissues, the clinical relevance of G6PD deficiency, and their importance in rapidly proliferating cells such as tumors. Together, glycolysis and the hexose monophosphate pathway represent core metabolic networks crucial for both energy generation and biosynthetic processes.