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The importance of A TP as the main source of chemical energy in living matter and its involve ment in cellular processes has long been recog nized. The primary mechanism whereby higher or ganisms, including humans, generate ATP is through mitochondrial oxidative phosphorylation. For the majority of organs, the main metabolic fuel is glucose, which in the presence of oxygen under goes complete combustion to CO 2 and H 2 0:The free energy (.:lG) liberated in this exergonic re action is partially trapped as ATP in two consecu tive processes: glycolysis (cytosol) and oxidative phosphorylation (mitochondria). The first produces 2 mol of ATP per mol of glucose, and the second 36 mol of ATP per mol of glucose. In the latter case, 6 mol of ATP are contributed from the oxidation of 2 mol of NADH generated in the cytosol during gly colysis and transferred into the mitochondria indi rectly through various "shuttle" systems. (In the a-glycerophosphate shuttle, the yield of ATP per NADH is reduced from 3 to 2 because the relevant mitochondrial dehydrogenase is a flavoprotein linked enzyme). Thus, oxidative phosphorylation yields 17-18 times as much useful energy in the form of ATP as can be obtained from the same amount of glucose by glycolysis alone. It is there fore not surprising that limitation of O 2 supply pro duces very damaging effects on cellular function. The brain is one of the organs that is particularly sensitive to lack of oxygen and in humans at rest is responsible for 20% of total O 2 consumption al though it accounts for only 2% of the body weight. in the function of the CNS? It will become evident from our discussion that only partial an swers to these questions are currently available. However, the search for these solutions involves some of the most exciting areas of contemporary neurochemistry. CONCENTRA nONS OF HIGH ENERGY PHOSPHATE COMPOUNDS IN MAMMALIAN BRAINBrain, like all other organs in the body, contains phosphorylated nucleotides that yield energy upon hydrolysis of their phosphate bond(s); the most im portant of these is the adenine nucleotide ATP. In addition, the CNS, in common with other excitable tissues, possesses another high energy reservoir, the creatine phosphate/creatine (PCr/Cr) system,

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Summary:This review analyzes, in some depth, results of studies on the effect of lowered temperatures on cerebral energy metabolism in animals under normal conditions and in some selected pathologic situations. In sedated and paralyzed mammals, acute uncomplicated 0.5-to 3-h hypothermia decreases the global cerebral metabolic rate for glucose (CMR glc ) and oxygen (CMRO 2 ) but maintains a slightly better energy level, which indicates that ATP breakdown is reduced more than its synthesis. Intracellular alkalinization stimulates glycolysis and independently enhances energy generation. Lowering of temperature during hypoxia-ischemia slows the rate of glucose, phosphocreatine, and ATP breakdown and lactate and inorganic phosphate formation, and improves recovery of energetic parameters during reperfusion. Mild hypothermia of 12 to 24-h duration after normothermic hypoxic-ischemic insults seems to prevent or ameliorate secondary failures in energy parameters. The authors conclude that lowered head temperatures help to protect and maintain normal CNS function by preserving brain ATP supply and level. Hypothermia may thus prove a promising avenue in the treatment of stroke and trauma and, in particular, of perinatal brain injury.

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