AGE-RELATED-CHANGES IN SWINE BRAIN CREATINE KINASE-CATALYZED P-31 EXCHANGE MEASURED IN-VIVO USING P-31 NMR MAGNETIZATION-TRANSFER

P-31 exchange rates through the creatine kinase-catalyzed interconvers ion of phosphocreatine and gamma-ATP were measured in a total of 27 mi niature swine ranging in age from 5 days preterm to 5 weeks old. A ste ep increase in the forward rate constant for P-31 exchange from phosph ocreatine (PCr) to gamma-ATP was observed between 2 days preterm and 3 days postterm, with a more gradual increase for older ages. In contra st, the [PCr]/[NTP] ratio measured by in vivo P-31 nuclear magnetic re sonance (NMR) remained constant throughout this age interval and close to unity. Forward and reverse rate constants and the rate of flux for P-31 exchange were equal to each other for both preterm and S-week-ol d animals, suggesting that the creatine kinase reaction is near-equili brium for this span of age. Multifrequency steady-state saturation of P-i and PCr compared to single-frequency saturation of PCr produced th e same extent of saturation transfer to gamma-ATP, and the saturation of P-i alone had no effect on the gamma-ATP P-31 NMR signal. These res ults suggest that even for immature swine brain, creatine kinase activ ity should be adequate to buffer against changes in [ATP] when there i s a mismatch between energy supply and energy demand, during condition s such as ischemia or hypoxia. The results from the present study indi cate the unlikelihood that previously reported discrepancies between f orward and reverse P-32 flux rates in rat brain (Shoubridge et al., FE BS Lett 140:288-292, 1982) were due to neglect of gamma-ATP to P-i exc hange. If the contribution of nonadenosine triphosphate to the in vivo rat brain P-31 NMR Signal is accounted for in the calculation of reve rse flux and a literature value for rat brain [PCr] is used in the cal culation of forward flux, then forward and reverse flux rates are equa l.