[Mechanisms regulating citric acid metabolism in the brain]

The changes in the rates of citrate biosynthesis and utilization in rat brain, liver, kidney and heart, produced by hypoxia, action of 2,4-DNP and thyreotoxicosis, were compared with changes of some regulatory parameters under the same conditions. The comparison of citrate-synthase activities, citrate levels in tissues and 14C-incorporation from different precursors into citric acid permitted us to establish that the biosynthesis of citrate in brain was more intensive than in other tissues studied. The main source of acetyl-CoA for citrate-synthase reaction in brain is the oxidation of pyruvate. The ratio of adenine nucleotides plays an important role in the control of citrate-synthase activity in brain, where the oxaloacetate control is not as significant as in liver. NAD-specific isocitrate dehydrogenase reaction was found to be the dominant pathway for citrate oxidation in brain: more than 60 percent of brain citrate were oxidized by NAD-ICDH, while less than 10 percent of citric acid were utilized by this enzyme in other tissues studied. The existance of an adenine nucleotide control of NAD-ICDH activity in brain may be an additional mechanism for the regulation of the first steps of energy metabolism in brain.