O2 is utilized in the brain almost entirely for the oxidation of carbohydrate [16]. The energy equivalent of the total cerebral metabolic rate is, therefore, approximately 20 W, or 0.25 kcal/min. If it is assumed that this energy is utilized mainly for the synthesis of high-energy phosphate bonds, that the efficiency of the energy conservation is approximately 20% and that the free energy of hydrolysis of the terminal phosphate of ATP is approximately 7 kcal/mol, then this energy expenditure can be estimated to support the steady turnover of close to 7 mmol, or approximately 4 × 1021 molecules, of ATP per minute in the entire human brain. The brain normally has no respite from this enormous energy demand. Cerebral O2 consumption continues unabated day and night. Even during sleep there is only a relatively small decrease in cerebral metabolic rate; indeed, it may even be increased in rapid eye movement (REM) sleep (see below).