Brain Metabolism and Activity

The Purine Salvage Pathway and the Restoration of Cerebral ATP: Implications for Brain Slice Physiology and Brain Injury

“…ATP critically regulates the ability of kinases to phosphorylate substrates, and is required for protein synthesis, both of which are important for commonly studied slice phenomena such as long-term potentiation (LTP) [19]. ATP also has signalling properties in its own right through at least seven ionotropic (P2X 1−7 ) and eight G protein-coupled receptors (GPCRs; P2Y 1,2,4,6,11,12,13,14 ), and indirectly through its metabolism to ADP (P2Y 1,12,13 agonist) and adenosine, which has pronounced actions on the CNS through its four GPCRs (A 1 , A 2A , A 2B , A 3 ) [20]. Moreover, the ratio of ATP:AMP critically regulates the activity of AMP-activated protein kinase (AMPK), an enzyme that is known to regulate a number of ion channels and which is increasingly being implicated in a host of CNS functions [21,22].…”

“…In the 1950s Henry McIlwain popularised the use of surgically isolated brain slices as a means to study in vitro the biochemical and electrical activity of the mammalian brain [1]. Whilst this was, and remains, an extremely valuable model system, it was clear to McIlwain that the brain slice was biochemically very different from the intact brain [2–7]. This appreciation had come from extensive studies in his own lab, but also from others, that had shown very rapid post mortem changes in the brains of animals, not least of which in ATP and phosphocreatine, which, by donating a phosphate to ADP, delays the loss of ATP (Fig.…”

The regulation of respiration during the assimilation of nitrogen in Torulopsis utilis

“…Much recent evidence converges to show that the rate ofcell respiration is closely dependent on assimilation and other endergonic reactions. For example, high rates of respiration or glycolysis have been found to accompany not only nitrogen assimilation but also the assimilation of glucose in yeast (Simon, 1953a), the anabolic processes of young seedlings (Folkes, Willis & Yemm, 1952), the accumulation of salts by roots (Milthorpe & Robertson, 1948;Robertson, Wilkins & Weeks, 1951), and, in animals, muscular (Fenn, 1927) and nervous activity (McIlwain, 1950). Current theories (see, for example, Dixon, 1949) have laid great stress on phosphorylation as the underlying mechanism whereby catabolic processes are regulated to meet the energy requirements of synthesis and other functional activities of the cell.…”

The inorganic phosphate and phosphocreatine of brain especially during metabolism in vitro

“…It appears likely that the rate of carbohydrate oxidation and glycolysis in tissues and the balance between these two processes are conditioned by the concentrations of labile phosphates and their breakdown products (Belitzer, 1939;Johnson, 1941; for an assessment in relation to brain, McIlwain, 1950). Such rates can be remarkably close in tissue slices to those normal to the tissue in vitro (Schmidt, Kety & Pennes, 1945).…”