Maturational increase in mouse brain creatine kinase reaction rates shown by phosphorus magnetic resonance.
In-vivo phosphorus fluxes in the reaction catalyzed by creatine kinase (CK) were measured in brains of mice from 3 to 40 days of age using high-field (8.45 T) phosphorus magnetic resonance and the saturation transfer technique. This technique gives the ratio of chemical flux to reactant concentration directly and allows the calculation of pseudo-rate constants for the forward direction from PC to ATP (kf) and for the reverse direction (kr). The spin-lattice relaxation times (T1) for phosphocreatine (PC) and for the nucleoside triphosphate (NTP) nuclei, estimated by the progressive saturation technique, did not change during this age period. The PC concentration doubled relative to the NTP concentration over the first month of life. The kf and the flux of phosphorus nuclei in the forward direction increased 2- to 3-fold in the very narrow time period from 12 to 15 days of age. Brain phosphorus flux from PC to ATP thus increased 4- to 6-fold in the first month of life. An increase at least that large occurred in the reverse direction, but the kr could not be measured consistently in the younger animals using the saturation transfer technique. Phosphorus fluxes were equal in the forward and reverse directions in the mature brain. The capacity to increase rates of glycolysis and tissue respiration in response to increased energy demand appears in the same narrow age period as the increase in CK-catalyzed reaction rates in the developing rodent brain. We propose that these coincident changes in brain energy metabolism reflect the maturation of mechanisms for coupling cell energy production to rapid changes in energy requirements.
Holtzman
D
D
Department of Neurology, Harvard Medical School, Children's Hospital Medical Center, Boston, MA 02115.
McFarland
E W
EW
Jacobs
D
D
Offutt
M C
MC
Neuringer
L J
LJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000254:growth & development / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009711:Nucleotides / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus
D009711:Nucleotides; D010725:Phosphocreatine; D010758:Phosphorus; D000255:Adenosine Triphosphate; D003402:Creatine Kinase