ABSTRACT
Glucose is stored as glycogen predominantly in liver and skeletal muscle. The absence of the key enzyme, glucose-6-phosphatase, precludes the muscle from releasing free glucose into the circulation for use by other tissues. Muscle glycogen serves as a glucose store solely for its own use. Glycogen is hydrolyzed (glycogenolysis) in both muscle and liver to glucose-1-phosphate by glycogen phosphorylase. Glucose-1-phosphate is isomerized to glucose-6-phosphate which serves as a substrate for two pathways: glycolysis and the pentose phosphate pathway. Under aerobic conditions, glycolysis converts glucose-6-phosphate to pyruvate, accompanied by the production of ATP via substrate-level phosphorylation at two steps in the pathway (4ATP/glucose-6phosphate). When oxygen supply is limited, pyruvate is reduced to lactate to enable glycolysis to continue. Lactate can serve as a substrate for gluconeogenesis. When oxygen supply is not limiting, however, pyruvate enters the mitochondrion and is oxidized to carbon dioxide and water, and then some of the energy released from this oxidation is used to drive the synthesis of ATP by the process of oxidative phosphorylation. Metabolism of glucose via glycolysis also generates intermediates for other metabolic pathways.
