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,