SUMMARY

• 16.1 Glycolysis Is an Energy-Conversion Pathway

  Glycolysis is the set of reactions that converts glucose into pyruvate. The 10 reactions of glycolysis take place in the cytoplasm. In the first stage, glucose is converted into fructose 1,6-bisphosphate by a phosphorylation, an isomerization, and a second phosphorylation reaction. Two molecules of ATP are consumed per molecule of glucose in these reactions, which are the prelude to the net synthesis of ATP. Fructose 1,6-bisphosphate is then cleaved by aldolase into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate, which are readily interconvertible. In the second stage, ATP is generated. Glyceraldehyde 3-phosphate is oxidized and phosphorylated to form 1,3-bisphosphoglycerate, an acyl phosphate with a high phosphoryl-transfer potential. This molecule transfers a phosphoryl group to ADP to form ATP and 3-phosphoglycerate. A phosphoryl shift and a dehydration form phosphoenolpyruvate, a second intermediate with a high phosphoryl-transfer potential. Another molecule of ATP is generated as phosphoenolpyruvate is converted into pyruvate. There is a net gain of two molecules of ATP in the formation of two molecules of pyruvate from one molecule of glucose.

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• 16.2 NAD⁺ Is Regenerated from the Metabolism of Pyruvate

  The electron acceptor in the oxidation of glyceraldehyde 3-phosphate is NAD⁺, which must be regenerated for glycolysis to continue. In aerobic organisms, the NADH formed in glycolysis transfers its electrons to O₂ through the electron-transport chain, which thereby regenerates NAD⁺. Under anaerobic conditions and in some microorganisms, NAD⁺ is regenerated by the reduction of pyruvate to lactate. In other microorganisms, NAD⁺ is regenerated by the reduction of pyruvate to ethanol. These two processes are examples of fermentations.

• 16.3 Fructose and Galactose Are Converted into Glycolytic Intermediates

  Although glucose is the most common monosaccharide fuel molecule, fructose and galactose also are frequently available. These monosaccharides must be converted into intermediates in the glycolytic pathway to be used as fuel. Fructose is phosphorylated to fructose 6-phosphate in most tissues. In the liver, fructose 1-phosphate is formed and cleaved to yield dihydroxyacetone phosphate and glyceraldehyde, which is subsequently phosphorylated to glyceraldehyde 3-phosphate. Galactose is converted into glucose 1-phosphate in a four-step process that includes UDP-glucose, the activated form of glucose. Glucose 1-phosphate is converted into glucose 6-phosphate by phosphoglucomutase.

• 16.4 The Glycolytic Pathway Is Tightly Controlled

  The glycolytic pathway has a dual role: (1) it degrades glucose to generate ATP, and (2) it provides building blocks for the synthesis of cellular components. The rate of conversion of glucose into pyruvate is regulated to meet these two major cellular needs. Under physiological conditions, the reactions of glycolysis are readily reversible, except for those catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase. Phosphofructokinase, the most important control element in glycolysis, is inhibited by high levels of ATP and citrate, and it is activated by AMP and fructose 2,6-bisphosphate. In the liver, this bisphosphate signals that glucose is abundant. Hence, phosphofructokinase is active when either energy or building blocks are needed. Hexokinase is inhibited by glucose 6-phosphate, which accumulates when phosphofructokinase is inactive. ATP and alanine allosterically inhibit pyruvate kinase, the other control site, and fructose 1,6-bisphosphate activates the enzyme. Consequently, pyruvate kinase is maximally active when the energy charge is low and glycolytic intermediates accumulate.

• 16.5 Metabolism in Context: Glycolysis Helps Pancreatic Beta Cells Sense Glucose

  The increase in the ratio of ATP/ADP that results from the metabolism of glucose to pyruvate closes K⁺ channels in the membranes of ß cells of the pancreas. The resulting change in the cellular ionic environment causes an influx of Ca²⁺, which, in turn, leads to insulin secretion. Insulin stimulates the uptake of glucose by muscle and adipose tissue.