Glucose metabolism
Glucose occupies a central position in the metabolism It is a major source of metabolic energy. It provides the precursors for the synthesis of other biomolecules. It is stored in polymeric form (as starch in plants and as glycogen in animals)
Glycolysis “Glyco” – “lysis”: breakdown of glucose monomer Gluconeogenesis “New” “genesis” of “glucose”: synthesizing glucose “from scratch” Used when supply of glycogen is exhausted Glycogen synthesis and degradation Storing glucose long-term and recovering it later Pentose phosphate pathway Used to generate pentoses (5-C sugars) Start with glucose Pathways of glucose metabolism
Each step is a different chemical reaction and is catalyzed by a different enzyme. Free energy released or consumed is transferred to carriers like ATP and NADH. Rate of pathway flux controlled by changing activity of individual enzymes. Multiple steps → greater energy recovery. Two general purposes of catabolic pathways Convert energy in molecules to more usable form. Create intermediates to be used in other pathways. Properties of glucose metabolism pathways
Major Pathways of Glucose Utilization Structural polymers Storage polymers Building blocks for DNA and RNA
Metabolites like glucose are often activated with a high-energy group before their catabolism. Glucose and other hexoses and hexose phosphates obtained from stored polysaccharides or dietary carbohydrates feed into the glycolytic pathway. Pyruvate formed under anaerobic conditions is reduced to lactate with electrons from NADH, recycling NADH to NAD+ and allowing continued glycolysis in the processes of lactate or alcohol fermentation. Gluconeogenesis is the synthesis of glucose from simpler precursors like pyruvate and lactate. Glycolysis and gluconeogenesis are reciprocally regulated so that both processes don’t occur simultaneously in a futile cycle. The pentose phosphate pathway is an alternative pathway for glucose oxidation. Key principles
Net equation: 10-step oxidation pathway Steps 1-5: energy investment phase Steps 6-10: energy payoff phase Enzyme name tells you what it does. Remember structure of glucose, then just follow the steps to get the other structures. Glycolysis 1 ×C6 2 ×C3
Overview of Glycolysis Essentially all cells carry out glycolysis Ten reactions - same in all cells - but rates differ Two steps: First step converts glucose to two glyceraldehyde-3-phosphate. Second step produces two pyruvates（丙酮酸） Products are pyruvate, ATP and NADH Three possible fates for pyruvate
Biological importance of glycolysis It can function aerobically or anaerobically, depending on the availability of oxygen and electron transport chain (ETC). Some special cells have no mitochondria and they rely completely on glucose as their metabolic fuel and metabolize it anaerobically. Glycolysis is the principle route for glucose metabolism, and is also the main pathway for the metabolism of fructose, galactose and other sugars derived from the diet. Glycolysis of glucose to provide ATP anaerobically is especially important, because skeletal muscles can perform under anoxic conditions. In the cancerous cells glycolysis proceeds at a very high rate, forming large amounts of pyruvate, which is reduced to lactate, leads to acidic environment and has implications for cancer therapy. [əˈnɒksɪk] 缺氧的
Free energy changes in glycolysis Three steps have large negative values of ΔG. These steps are potential flux-control points. Slower steps-pathway can only go as far as its slowest step