Muscle can utilize a variety of fuels-glucose, fatty acids, and ketone bodies. Skeletal muscle varies widely in its energy demands and the fuels it consumes, in line with its wide variations in activity.

In resting muscle, fatty acids represent the major energy source; during exertion, glucose is the primary source. Early in a period of exertion, glucose comes from mobilization of the muscle's glycogen reserves.

Skeletal muscle stores about three-fourths of the total glycogen in humans, with most of the rest being stored in the liver. Glucose released from muscle glycogen cannot be released from the cell for use by other tissues. Muscle lacks the enzyme glucose-6-phosphatase, so glucose phosphates derived from glycogen cannot be converted to glucose and released from the cell.

During exertion, the rate of glycolysis in muscle exceeds that of the citric acid cycle, so lactate accumulates and is released. Another metabolic product is alanine, produced via transamination from pyruvate in the glucose - alanine cycle (see Figure 20.14 and here). Both lactate and alanine are transported through the bloodstream to the liver, where they are reconverted through gluconeogenesis to glucose, for return to the muscle and other tissues by the Cori cycle (see Figure 16.5 and here.).

Muscle contains another readily mobilizable source of energy-its own protein. However, the breakdown of muscle protein to meet energy needs is both energetically wasteful and harmful to an animal, which must move about in order to survive. Protein breakdown is regulated so as to minimize amino acid catabolism except in starvation.

Muscle has an additional energy reserve in creatine phosphate, which generates ATP without the need for metabolizing fuels (see here). This reserve is exhausted early in a period of exertion and must be replenished, along with glycogen stores, as muscle rests after prolonged exertion.