Brain ATP metabolism in hypoxia resistant mice fed guanidinopropionic acid.
Feeding beta-guanidinopropionic acid (GPA), a competitive inhibitor of creatine transport, decreases mortality and increases brain ATP stability in hypoxic mice. To study brain ATP metabolism in GPA-fed animals, respiratory rates were measured in grey matter and white matter slices as well as cerebral hemisphere mitochondria from GPA-fed mice and rats. Creatine kinase and adenylate kinase activities were measured in rat cerebral grey matter and white matter. Respiratory rates and oxidative phosphorylation were the same in GPA-fed mice and control mice. The adenylate kinase activity increased 50% and creatine kinase showed a small decrease in grey matter. In white matter, creatine kinase increased 50% while adenylate kinase decreased. Thus, GPA produces opposite adaptive changes in adenylate kinase and creatine kinase in grey matter and in white matter. These results suggest that the creatine kinase reaction in grey matter acts to regulate cellular ADP and ATP concentrations.
Department of Neurology, Children's Hospital and Harvard Medical School, Boston, Mass., USA.
D
D
Holtzman
M
M
Brown
E
E
O'Gorman
E
E
Allred
T
T
Wallimann
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism; D004351:Drug Resistance / Q000502:physiology; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D010101:Oxygen Consumption / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects
D006146:Guanidines; D009840:Oligomycins; D011422:Propionates; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D000263:Adenylate Kinase; C005775:guanidinopropionic acid