In glycolysis, glucose-6-phosphate, derived either from the degradative phosphorylation of glycogen or from the phosphorylation of glucose in serum, is broken down into two molecules of acetyl coenzyme A (CoA). This process may take place in the absence of oxygen, yet three molecules of ATP are generated for each molecule of glucose used. Acetyl CoA enters the citric acid (Krebs) cycle, which generates the reduced forms of flavin adenine dinucleotide (FADH₂) and nicotinamide adenine dinucleotide (NADH). Both of these can fuel the conversion of adenosine diphosphate (ADP) into ATP only through the cytochrome oxidative pathway, which involves the reduction of oxygen to water. (The glycolytic pathway also generates NADH, whereas the citric acid cycle generates guanosine triphosphate [GTP], which can contribute a high-energy phosphate to ADP and thus make ATP.) Thus, whereas only 3 molecules of ATP are generated under anaerobic conditions, 35 molecules of ATP are generated by oxygenrequiring steps in the metabolism of one molecule of glucose derived from glycogen.

The level of ATP in muscle must remain high; it does not decrease substantially, even during continuous contraction, because muscle fibers have a built-in ATPbuffering system. Energy is stored as creatine phosphate. If the ATP level falls, a small amount of creatine phosphate transfers a phosphate into ADP, forming creatine and regenerating ATP. However, even this reserve pool is not unlimited and can be depleted by intense exercise.