The in vivo inactivation by cyanide of brain cytochrome oxidase and its effect on glycolysis and on the high energy phosphorus compounds in brain.

The symptomatology Jf cyanide poisoning has been known for well )ver 100 years. Claude Bernard (1) was among the first to stress the inhibitory effect on the respiration of higher animals. The work of Keilin (2) and of Stotz (3) has shown that cyanide ion combines in vitro with :ytochrome oxidase and thereby interferes with the utilization of molecular oxygen by the tissue oxidation-reduction systems. It has also been demonstrated that the utilization of molecular oxygen is coupled with phosphorylation reactions (4-7), and Lipmann (8) has emphasized the role of aerobic metabolism in the resynthesis of high energy phosphorus compounds. LePagel analyzed the tissues of rats subjected to experimental shock in a Noble-Collip rotating drum and observed elevated lactic acid and inorganic phosphate, low glycogen, adenosine triphosphate depletion, some phosphocreatine depletion, and an abnormal accumulation of phosphopyruvate. Proger, Decaneas, and Schmidt (9) have recently found that the readily hydrolyzable phosphorus fraction of kidney and heart tissue was decreased when rats were exposed to low oxygen tensions. These results indicate that in the intact animal also the resynthesis of high energy phosphorus compounds is coupled with oxidative processes. The present experiments were undertaken, first, to determine whether brain tissue from cyanide-poisoned rats showed a diminution in cytochrome oxidase activity and, secondly, to study in some detail the distribution of glycogen, lactic acid, and phosphorylated intermediates in such tissue, particularly with reference to the distribution pattern of high energy phosphorus compounds.