Chapter 16: Glycolysis & Gluconeogenesis

Glycolysis & Gluconeogenesis details the ten-step glycolytic process occurring in the cytoplasm, where one molecule of glucose is metabolized into two molecules of pyruvate, resulting in a net gain of two ATP and two NADH molecules. The summary explains the pathway's two distinct stages: the investment phase, which traps glucose using hexokinase and commits it to metabolism via phosphofructokinase, and the energy-generation phase, where high-phosphoryl-transfer compounds like 1,3-bisphosphoglycerate and phosphoenolpyruvate drive the synthesis of ATP. Key biochemical mechanisms are highlighted, including the induced-fit conformational changes of kinases to exclude water and the use of thioester intermediates to couple favorable oxidations with unfavorable phosphorylations. The text explores the anaerobic fates of pyruvate, describing how fermentation converts pyruvate into lactate or ethanol to regenerate the NAD plus required for glycolysis to continue in the absence of oxygen. It also addresses the metabolism of non-glucose sugars, explaining how fructose and galactose enter the glycolytic pathway and the clinical consequences of enzyme deficiencies, such as lactose intolerance, cataracts, and galactosemia. Transitioning to gluconeogenesis, the description outlines how the liver synthesizes glucose from non-carbohydrate precursors like lactate, amino acids, and glycerol during fasting. It emphasizes that gluconeogenesis is not a simple reversal of glycolysis but requires unique enzymes—pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase—to bypass the three thermodynamically irreversible steps of glycolysis. The summary provides an in-depth analysis of reciprocal regulation, showing how energy charge (ATP to AMP ratio) and allosteric effectors like citrate and alanine control flux through these pathways to prevent futile cycling. A central focus is placed on the hormonal control of metabolism by insulin and glucagon, specifically regulating the bifunctional enzyme that controls the levels of fructose 2,6-bisphosphate, a potent signal molecule that switches the liver between glucose consumption and production. Finally, the text covers metabolic integration topics, including the Cori cycle which recycles lactate between muscle and liver, the diverse family of GLUT transporters, and the Warburg effect, where cancer cells utilize aerobic glycolysis to support rapid growth.