Relative phosphocreatine and nucleoside triphosphate concentrations in cerebral gray and white matter measured in vivo by 31P nuclear magnetic resonance

Tsuji, Miles; Mulkern, Robert V.; Cook, Colin U.; Meyers, Ron; Holtzman, David

doi:10.1016/0006-8993(95)01229-x

Cited by 23 publications

(25 citation statements)

References 21 publications

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“…Turnover of ATP in gray matter is higher and more variable than in white matter. The creatine (Cr)/creatine kinase (CK)/phosphocreatine (PCr) system is closely coupled to ATP metabolism and shows similar regional heterogeneity in brain [4,5]. CK (EC 2.7.3.2) catalyzes the reversible transfer of phosphoryl groups between PCr and ATP (Cr + ATP ←→ F4 PCr + ADP + H + ).…”

Section: Introductionmentioning

confidence: 99%

“…The CrT facilitates the movement of Cr across the plasma membrane against a concentration gradient via a sodium-and chloride-dependent, high-affinity uptake process [9]. Piglet and rabbit brains show higher PCr concentration, and lower Mi-CK activity and Cr content in white matter compared to gray matter [4,5,10,11]. Developmentally, brain PCr/nucleoside triphosphate (NTP) ratio increases between 5 and 25 postnatal days in rat and between 5 and 30 days in rabbit, probably due to increased PCr in both species [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Kekelidze

Khait²,

Togliatti³

et al. 2000

Dev Neurosci

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Systemic creatine (Cr) supplementation increases brain phosphocreatine (PCr) and prevents hypoxic seizures in 15-day-old rabbits . Between 5 and 30 days of age during normal development, rabbit gray matter mitochondrial creatine kinase (Mi-CK) increases 400% while cytosolic CK (BB-CK) increases 60%. In white matter, both isoenzymes show smaller, similar increases (40%) during this period. The Cr transporter protein decreases 60% between 5 and 15 days in both regions. In vivo CK rate constants measured by ³¹P nuclear magnetic resonance increase 30% between 10 and 20 days, and then fall 50% between 20 and 30 days in predominantly gray matter slices. Similar maturational changes are seen in predominantly white matter slices. Injecting Cr at 15 days does not significantly change BB-CK or Mi-CK isoenzymes or the in vivo CK reaction rate constants. Thus, the largest change in the CK system associated with suppression of hypoxic seizures in Cr-treated rabbits is increased PCr in gray and white matter.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Kekelidze

Khait²,

Togliatti³

et al. 2000

Dev Neurosci

Self Cite

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“…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.…”

Section: Discussionmentioning

confidence: 63%

“…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.…”

Section: Discussionmentioning

confidence: 90%

“…These observations suggest that GPA replaces creatine in a cerebral compartment in which the CK reaction rate is high and into which creatine is transported rather than synthesized [8]. Recent studies suggest that this compartment may be white matter, which has a rapid CK reaction rate, low mitochondrial CK versus cytosolic B-CK, a high phosphocreatine:NTP ratio, and slower and more stable ATP turnover compared to grey matter [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Brain ATP Metabolism in Hypoxia Resistant Mice Fed Guanidinopropionic Acid

Holtzman

Brown²,

O’Gorman³

et al. 1998

Dev Neurosci

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Feeding β-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.

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Mental retardation and behavioral problems as presenting signs of a creatine synthesis defect

et al. 2000

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Relative phosphocreatine and nucleoside triphosphate concentrations in cerebral gray and white matter measured in vivo by 31P nuclear magnetic resonance

Cited by 23 publications

References 21 publications

Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Brain ATP Metabolism in Hypoxia Resistant Mice Fed Guanidinopropionic Acid

Mental retardation and behavioral problems as presenting signs of a creatine synthesis defect

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