SUMMARY

• 17.1 Glucose Can Be Synthesized from Noncarbohydrate Precursors

  Gluconeogenesis is the synthesis of glucose from noncarbohydrate sources, such as lactate, amino acids, and glycerol. Several of the reactions that convert pyruvate into glucose are common to glycolysis. Gluconeogenesis, however, requires four new reactions to bypass the three irreversible reactions in glycolysis. In two of the new reactions, pyruvate is carboxylated in mitochondria to oxaloacetate, which, in turn, is decarboxylated and phosphorylated in the cytoplasm to phosphoenolpyruvate. Two high phosphoryl-transfer potential molecules power these reactions, which are catalyzed by pyruvate carboxylase and phosphoenolpyruvate carboxykinase, respectively. The other distinctive reactions of gluconeogenesis are the hydrolyses of fructose 1,6-bisphosphate and glucose 6-phosphate, which are catalyzed by specific phosphatases. A major precursor for gluconeogenesis by the liver is lactate and produced by active skeletal muscle. The formation of lactate during intense muscular activity buys time and shifts part of the metabolic burden from muscle to the liver.

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• 17.2 Gluconeogenesis and Glycolysis Are Reciprocally Regulated

  Gluconeogenesis and glycolysis are reciprocally regulated so that one pathway is less active while the other is highly active. Phosphofructokinase and fructose 1,6-bisphosphatase are key control points. Fructose 2,6-bisphosphate, an intracellular signal molecule present at higher levels when glucose is abundant, activates glycolysis and inhibits gluconeogenesis by regulating these enzymes. Pyruvate kinase and pyruvate carboxylase are regulated by other effectors so that both are not maximally active at the same time. Allosteric regulation and reversible phosphorylation, which are rapid, are complemented by transcriptional control, which takes place in hours or days.

• 17.3 Metabolism in Context: Precursors Formed by Muscle Are Used by Other Organs

  Lactate that is generated by glycolysis in contracting muscle is released into the bloodstream. This lactate is removed from the blood by the liver and is converted into glucose by gluconeogenesis. This metabolic cooperation between muscle and liver is called the Cori cycle.