Flow-Metabolism Coupling: The New Synthesis Albert Gjedde Århus University, Århus, Denmark

In reality, brain function is reflected in the regional rates of energy metabolism, but blood flow rates are often used to test hypotheses of functional organization. Thus, the variability of flow-metabolism coupling in brain has become a major obstacle to the correct interpretation of functional brain maps. Inclusion of blood-brain transfer of oxygen in the regulation of oxidative metabolism in brain regions revealed a novel mechanism of flow-metabolism coupling. In this mechanism, nitric oxide (NO) is involved in blood flow regulation but also maintains the appropriate oxidative metabolism by adjustment of the affinity of cytochrome oxidase towards oxygen. It will be shown that interactions of oxygen and NO at both cytochrome oxidase and nitric oxide synthase match the affinities of these two enzymes towards their respective substrates to the oxygen requirement of the tissue and so explain the known properties of flow-metabolism coupling.