Figure 5.Coupling of reactions in energy metabolism and the operation of “futile cycles” (30). Metabolism of fuel generates a stoichiometric amount of NADH and FADH2. Oxidation of NADH and FADH2 results in 10 and 6 protons, respectively, being pumped out of the mitochondrial matrix. Three protons enter via ATP synthase in order to synthesize one molecule of ATP from ADP and Pi. One additional proton enters the matrix as it is co-transported with Pi via the phosphate carrier. ATP is then utilized to perform a fixed amount of work. The major consumers of ATP are shown above. Muscle relaxation, ion leaks, protein degradation and dephosphorylation create the possibility for “futile cycles”. See Rolfe and Brown (10) for a complete analysis of the concept of coupling with respect to reactions in energy metabolism. This figure was adapted from reference (29).