Creatine Kinase-Catalyzed Reaction Rate in the Cyanide-Poisoned Mouse Brain

Holtzman, David; Offutt, Martin; Tsuji, Miles; Neuringer, L. J.; Jacobs, Danny O.

doi:10.1038/jcbfm.1993.18

Cited by 17 publications

(9 citation statements)

References 37 publications

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“…5, P Ͻ 0.004 in Ho mice; P Ͻ 0.04 in Wt mice). This post-hypoxic decrease in brain CK rate constant was described previously in cyanide poisoned rats (Holtzman et al, 1993a).…”

Section: Resultssupporting

confidence: 82%

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Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent

Kekelidze

Khait

Togliatti

et al. 2001

J of Neuroscience Research

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In cerebral gray matter, ATP concentration is closely maintained despite rapid, large increases in turnover and low substrate reserves. As seen in vivo by (31)P nuclear magnetic resonance (NMR) spectroscopy, brain ATP is stable early in seizures, a state of high energy demand, and in mild hypoxia, a state of substrate deficiency. Like other tissues with high and variable ATP turnover, cerebral gray matter has high phosphocreatine (PCr) concentration and both cytosolic and mitochondrial creatine kinase (UbMi-CK) isoenzymes. To understand the physiology of brain creatine kinases, we used (31)P NMR to study PCr and ATP regulation during seizures and hypoxia in mice with targeted deletion of the UbMi-CK gene. The baseline CK reaction rate constant (k) was higher in mutants than wild-types. During seizures, PCr and ATP decreased in mutants but not in wild-types. The k-value for the CK catalyzed reaction rate increased in wild-types but not in the mutants. Hypoxic mutants and wild-types showed similar PCr losses and stable ATP. During recovery from hypoxia, brain PCr and ATP concentrations returned to baseline in wild-types but were 20% higher than baseline in the mutants. We propose that UbMi-CK couples ATP turnover to the CK catalyzed reaction rate and regulates ATP concentration when synthesis is increased.

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“…5, P Ͻ 0.004 in Ho mice; P Ͻ 0.04 in Wt mice). This post-hypoxic decrease in brain CK rate constant was described previously in cyanide poisoned rats (Holtzman et al, 1993a).…”

Section: Resultssupporting

confidence: 82%

“…The hyperoxygenated gray matter shows increased PCr concentration, whereas ATP is unchanged . After a period of moderate cellular hypoxia produced by cyanide, the CK catalyzed reaction rate decreases 80% for at least 2 hr (Holtzman et al, 1993a).…”

mentioning

confidence: 99%

Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent

Kekelidze

Khait

Togliatti

et al. 2001

J of Neuroscience Research

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“…A tentative conclusion from these observations is that the maturational appearance of the Mi-CK isoenzyme in functional association with some of the B-CK isoenzyme effects a large increase in the average flux catalyzed by the enzyme complex. Measuring the adult brain isoenzyme activities under conditions in which the in vivo CK catalyzed reac tion rate is reduced to the rate in the immature brain will directly test this hypothesis on the roles of the CK isoen zymes in the total CK activity [7,24],…”

Section: Discussionmentioning

confidence: 99%

“…Like other cell systems characterized by fluctuat ing energy requirements, the brain contains both cytoso lic creatine kinase (B-CK) and mitochondrial CK (Mi-CK) isoenzymes [4,5]. In analogy with the heart, it has been suggested that the CK catalyzed reaction rate in brain, measured in vivo by NMR spectroscopy, may re-fleet energy demand and ATP turnover more directly than do the concentrations of ATP or PC r [6,7], Two primary physiological functions have been suggested for the PC r/C K system in these tissues [5,8]. The first is a temporal buffer role in which PC r contributes phosphoryl groups for the resynthesis of ATP.…”

Section: Introductionmentioning

confidence: 99%

Functional Maturation of Creatine Kinase in Rat Brain

et al. 1993

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The physiological role of the phosphocreatine (PCr)/creatine kinase (CK) system has been studied in rat brain by comparing maturational changes in in vivo CK-catalyzed reaction rate and activities of CK isoenzymes. The CK-catalyzed reaction rates, measured by ³¹P-nuclear magnetic resonance spectroscopy, increased 4-fold between 12 and 17 days of age. The mitochondrial CK (Mi-CK) isoenzyme, as a percentage of total CK, increased to the same extent over this relatively narrow age period. Cytosolic CK (B-CK) was active earlier and, with the total CK activity, increased steadily over a longer time course. An immunohistochemical study of cerebellum showed Mi-CK predominantly in gray matter, while the cytosolic CK was present in rather large concentrations in both gray and white matter. In the molecular layer, B-CK was most prominent in the Bergmann glial cells, while Mi-CK was more prominent in Purkinje neurons. During development a redistribution of Mi-CK from the Purkinje cell bodies to their processes was observed. These results point to regional differences in CK content and in isoenzyme-specific localizations. The increase in CK activity is temporally coincident with the maturational appearance of closely coupled decreases in brain PCr and ATP during hypoxia. These maturational changes suggest that the activity of the PCr/CK system, particularly the Mi-CK isoenzyme, is central in regulation of brain ATP.

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“…k PCr→γ -ATP and metabolite concentrations pre-and postseizure were taken from Holtzman et al (12), who used TR = 10 s and θ = 90…”

Section: Simulation Parameter Selection For Brainmentioning

confidence: 99%

Optimized Pulse Parameters for Reducing Quantitation Errors Due to Saturation Factor Changes in Magnetic Resonance Spectroscopy

Galbán

Spencer

2002

Journal of Magnetic Resonance

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Creatine Kinase-Catalyzed Reaction Rate in the Cyanide-Poisoned Mouse Brain

Cited by 17 publications

References 37 publications

Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent

Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent

Functional Maturation of Creatine Kinase in Rat Brain

Optimized Pulse Parameters for Reducing Quantitation Errors Due to Saturation Factor Changes in Magnetic Resonance Spectroscopy

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