Chapter 14 Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway
We begin with the major pathways of glucose metabolism: glycolysis and fermentation, gluconeogenesis, and the pentose phosphate pathway. Glucose occupies a central position in the metabolism of plants, animals, and many microorganisms. It is relatively rich in potential energy, and thus a good fuel; the complete oxidation of glucose to carbon dioxide and water proceeds with a standard free-energy change of . By storing glucose as a high molecular weight polymer such as starch or glycogen, a cell can stockpile large quantities of hexose units while maintaining a relatively low cytosolic osmolarity. When energy demands increase, glucose can be released from these intracellular storage polymers and used to produce ATP either aerobically or anaerobically.
Glucose is not only an excellent fuel, but also a remarkably versatile precursor, capable of supplying a huge array of metabolic intermediates for biosynthetic reactions. A bacterium such as Escherichia coli can obtain from glucose the carbon skeletons for every amino acid, nucleotide, coenzyme, fatty acid, or other metabolic intermediate it needs for growth. A comprehensive study of the metabolic fates of glucose would encompass hundreds or thousands of transformations. In animals and vascular plants, glucose has four major fates: it may be (1) used in the synthesis of complex polysaccharides destined for the extracellular space; (2) stored in cells (as a polysaccharide or as sucrose); (3) oxidized to a three-carbon compound (pyruvate) via glycolysis to provide ATP and metabolic intermediates; or (4) oxidized via the pentose phosphate (phosphogluconate) pathway to yield ribose 5-phosphate for nucleic acid synthesis and NADPH for reductive biosynthetic processes (Fig. 14-1).
FIGURE 14-1 Major pathways of glucose utilization. Although not the only possible fates for glucose, these four pathways are the most significant in most cells.
Organisms that do not have access to glucose from other sources must make it. Photosynthetic organisms make glucose by first reducing atmospheric to trioses, then converting the trioses to glucose. Nonphotosynthetic cells make glucose from simpler three- and four-carbon precursors by the process of gluconeogenesis, effectively reversing glycolysis in a pathway that uses many of the glycolytic enzymes.
These principles are central to understanding glucose metabolism, but many apply to all metabolic pathways:
Metabolites like glucose are often activated with a high-energy group before their catabolism. Glycolysis is a nearly universal 10-step metabolic pathway for producing ATP by the oxidation of glucose. In this process, two molecules of ATP are invested to activate glucose, but the products of the pathway include four ATP, as well as NADH (a form of reducing power) and the triose pyruvate, which can be metabolized further in other pathways.
Glucose and other hexoses and hexose phosphates obtained from stored polysaccharides or dietary carbohydrates feed into the glycolytic pathway. By using a common pathway for a number of starting materials, the cell economizes on the number of enzymes that must be synthesized and simplifies the regulation of the common pathway.
Pyruvate formed under anaerobic conditions is reduced to lactate with electrons from NADH, recycling NADH to and allowing continued glycolysis in the processes of lactate or alcohol fermentation. Manipulation of the fermentable material and the microorganisms present allows the synthesis of a variety of industrial products and foods.
Gluconeogenesis is the synthesis of glucose from simpler precursors like pyruvate and lactate. Although it uses seven of the ten enzymes that also act in glycolysis, gluconeogenesis must bypass three of the most exergonic steps in glycolysis with energetically favorable reactions unique to gluconeogenesis.
Glycolysis and gluconeogenesis are reciprocally regulated so that both processes don’t occur simultaneously in a futile cycle. Most regulatory mechanisms act on reactions that are unique to each pathway.
The pentose phosphate pathway is an alternative pathway for glucose oxidation. It yields pentoses for nucleotide synthesis and reduced cofactors for biosynthesis of fatty acids, sterols, and many other compounds.
Metabolites like glucose are often activated with a high-energy group before their catabolism. Glycolysis is a nearly universal 10-step metabolic pathway for producing ATP by the oxidation of glucose. In this process, two molecules of ATP are invested to activate glucose, but the products of the pathway include four ATP, as well as NADH (a form of reducing power) and the triose pyruvate, which can be metabolized further in other pathways.
Glucose and other hexoses and hexose phosphates obtained from stored polysaccharides or dietary carbohydrates feed into the glycolytic pathway. By using a common pathway for a number of starting materials, the cell economizes on the number of enzymes that must be synthesized and simplifies the regulation of the common pathway.
Pyruvate formed under anaerobic conditions is reduced to lactate with electrons from NADH, recycling NADH to and allowing continued glycolysis in the processes of lactate or alcohol fermentation. Manipulation of the fermentable material and the microorganisms present allows the synthesis of a variety of industrial products and foods.
Gluconeogenesis is the synthesis of glucose from simpler precursors like pyruvate and lactate. Although it uses seven of the ten enzymes that also act in glycolysis, gluconeogenesis must bypass three of the most exergonic steps in glycolysis with energetically favorable reactions unique to gluconeogenesis.
Glycolysis and gluconeogenesis are reciprocally regulated so that both processes don’t occur simultaneously in a futile cycle. Most regulatory mechanisms act on reactions that are unique to each pathway.
The pentose phosphate pathway is an alternative pathway for glucose oxidation. It yields pentoses for nucleotide synthesis and reduced cofactors for biosynthesis of fatty acids, sterols, and many other compounds.