Phosphocreatine and Creatine H Kinase in Piglet Cerebral Gray and White Matter in situ

Abstract

Rates of adenosine triphosphate (ATP) metabolism are higher in cerebral gray matter than in white matter. Like other excitable tissues, brain contains a phosphocreatine (PCr)/creatine kinase (CK)/ATP system including cytosolic (B-CK) and mitochondrial (Mi-CK) isozymes. High B-CK activity is present in white and gray matter while Mi-CK is mostly in gray matter. An in situ localizing ³¹P-NMR technique, one-dimensional chemical shift imaging (1D-CSI), has been used to study the PCr/CK/ATP system in these regions. In the metabolically mature 4-week-old piglet, the PCr/nucleoside triphosphate (NTP) ratio measured by the 1D-CSI technique is at least 50% higher in white than gray matter. Total creatine (Cr), ATP, and total NTP concentrations are the same in rapidly frozen rat white and gray matter, suggesting that the PCr/Cr ratio is much higher in white matter. The PCr increases more in gray than white matter between 4 days and 4 weeks of age in piglet brain. The CK catalyzed reaction rate constant, measured by combining the saturation transfer experiment with the 1D-CSI, is also much higher in white than gray matter at both ages. The postnatal maturational increase in the CK rate constant is greater in gray matter. In summary, these differences in PCr concentration and CK reaction rates and isozymes characterize two physiologically different PCr/CK/ATP systems in gray and white matter.

'Hot Spots' of Creatine Kinase Localization in Brain: Cerebellum, Hippocampus and Choroid Plexus

“…These results together with recent findings that B-CK expression can be highly upregulated by cAMP-dependent processes [18], indicate that the CK system in brain shows developmental [34] and physiological statedependent dynamics [18], and that B-CK plays an impor tant function in astrocytes and oligodendrocytes 120, 22], and thus in the white matter of the brain [26]. Interesting in this respect is the finding that the amount of cytosolic muscle-type M-CK found in brain seems to be agedependent [31].…”

“…18. 17, 13 and 12 pg of B-CK per mg soluble protein of cerebellar white matter, cerebellar cortex, brain stem, cerebral cortex and cerebral white matter, respectively [23], as well as with localized "P-NMR saturation trans fer measurements, showing, in contrast to previous mea surements [24], a higher PCr/NTP ratio in white com pared to gray matter [25], and a higher CK-catalyzed reaction flux in white versus gray matter of the cerebral hemispheres [26], Creatine Kinase Isoenzymes in Cerebellum. Hippocampus, and Choroid Plexus With respect to the cellular and subcellular localiza tion of CK isoenzymes in brain, rat and chicken cerebel lum has been studied most thoroughly so far.…”

Brain ATP Metabolism in Hypoxia Resistant Mice Fed Guanidinopropionic Acid

“…The variation in specific metabolic adaptations apparent in different tissues suggests specific differences in regulation of enzymes of ATP and ADP metabolism and in the physiology of the CK reaction (table 5). This variation in adaptive responses is also seen in cerebral grey matter and white matter, in which there are different rates of ATP metabolism, CK reactant concentrations, and isoenzyme activities [9,10,17]. Changes in ATP metabolism suggest that the CK system plays a central role in the physiology of brain cellular energy metabolism.…”

“…The hypothesis for this study was that altered mitochondrial respiration is the mechanism for resistance to hypoxia. These changes were expected to be greater in white matter than in grey matter, based on the faster CK reaction rate and higher phosphocreatine concentration in white matter [9,17]. However, these hypotheses were not supported, since only small differences in respiratory properties and oxidative phosphorylation were seen in brain mitochondria and slices from GPA-fed mice compared to controls.…”

Introduction: Metabolic Trafficking Comes of Age in the Decade of the Brain

“…Several investigators including Arne Schousboe [7], David Holtzman [8], Leif Hertz [9] and Mary McKenna [10] presented data which give further insight into the complex regulation of metabolism in astrocytes. The compartmentation of specific biochemi cal pathways which leads to an absolute requirement for metabolic trafficking is most evident from the elegant studies of the visual system by Marcos Tsacopoulos and his coworkers [11] from Geneva, whose work clearly demonstrates the intercellular trafficking of metabolites between photoreceptor cells and Müller cells in the retina.…”