The forward and reverse rates through the creatine-kinase (CK) catalyzed reaction, phosphocreatine + ADP+ H+ kf in equilibrium with kr creatine + ATP in the in vivo monkey brain were measured using the techniques of saturation transfer (ST) and inversion transfer (IT) 31P nuclear magnetic resonance (NMR) spectroscopy. Independent checks on the ST apparent longitudinal relaxation (tau) data could be obtained from the parameters determined from the IT analyses. At near-equilibrium it is assumed that the forward-to-reverse flux ratio lies close to 1.0. In the monkey brain the value for the forward-to-reverse flux ratio obtained is 1.37 +/- 0.26 calculated from ST with average tau values from IT initial slopes, a value which is not significantly different from unity. The present NMR data point to the CK reaction in the living monkey brain being maintained at or near equilibrium.

ABSTRACT31P magnetic resonance imaging with chemical-shift discrimination by selective excitation has been employed to determine the phosphocreatine (PCr) distribution in the brains of three juvenile macaque monkeys. PCr images were also obtained while saturating the resonance of the -phosphate of ATP, which allowed the investigation of the chemical exchange between PCr and the v-phosphate of ATP catalyzed by creatine kinase. Superposition of the PCr images over the proton image of the same monkey brain revealed topological variations in the distribution of PCr and creatine kinase activity. PCr images were also obtained with and without visual stimulation. In two out of four experiments, an apparently localized decrease in PCr concentration was noted in visual cortex upon visual stimulation. This result is interpreted in terms of a possible role for the local ADP concentration in stimulating the accompanying metabolic response. A D P 3 --P + H+ -ATP-+ H20Positron emission tomography (PET) studies on humans have shown that with visual stimulation blood flow and glucose consumption are increased (1-3). Localized proton MR studies have revealed a short-term increase in lactate concentration in the human brain upon visual stimulation (4). Thus it may be surmised from both PET and MR studies that glycolysis is important in visual stimulation. The local increase in cerebral oxygen consumption (mean = 5%, as measured by PET) due to somatosensory stimulation is less than the corresponding local increase in cerebral blood flow (mean = 29%) (5). Despite the small increase in the oxygen consumption noted in these PET studies, there appears to be a role for oxidative phosphorylation, although it seems from these studies that over longer times the role of the glycolysis reaction is significant. The role of the CK reaction is in provision and transport of ATP, but the question whether visual stimulation results in any increase in CK activity has not yet been addressed by these PET studies or by MR techniques.A further point is the interaction of these three pathways of putative energy synthesis. An intermediate common to all three pathways is ADP. The local concentration of free ADP may determine flux through oxidative phosphorylation (6); it may also influence flux through glycolysis at one or more sites but, particularly indirectly, through allosteric effects of ATP or AMP on phosphofructokinase (7). The concentration of ADP is in turn determined by equilibrium reactions, among which CK is most significant (8). We may, therefore, expect to obtain useful information about all three reactions by observation of PCr concentration and determination of the equilibrium of CK, from which ADP concentration can be calculated.The great heterogeneity of cerebral circulation and metabolism observed in PET studies leaves room for doubt about MR assays, which are only performed at a single time point and confined to the anticipated region of interest. To assess the response of the CK reaction to visual stimulation, it would be helpful to ...

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