BRAIN ATP METABOLISM IN HYPOXIA RESISTANT MICE FED GUANIDINOPROPIONICACID

Feeding beta-guanidinopropionic acid (GPA), a competitive inhibitor of creatine transport, decreases mortality and increases brain ATP stabi lity in hypoxic mice. To study brain ATP metabolism in GPA-fed animals , respiratory rates were measured in grey matter and white matter slic es as well as cerebral hemisphere mitochondria from GPA-fed mice and r ats. Creatine kinase and adenylate kinase activities were measured in rat cerebral grey matter and white matter. Respiratory rates and oxida tive phosphorylation were the same in GPA-fed mice and control mice. T he adenylate kinase activity increased 50% and creatine kinase showed a small decrease in grey matter. In white matter, creatine kinase incr eased 50% while adenylate kinase decreased. Thus, GPA produces opposit e adaptive changes in adenylate kinase and creatine kinase in grey mat ter and in white matter. These results suggest that the creatine kinas e reaction in grey matter acts to regulate cellular ADP and ATP concen trations.