Disease relevance of phosphocreatine

• Ten minutes of ischemia caused quiescence, a fall in interstitial pH (from 7.2 +/- 0.01 to 6.1 +/- 0.8), creatine phosphate (CP), and ATP (from 54.5 +/- 5.0 and 25.0 +/- 1.9 to 5.0 +/- 1.1 and 15.3 +/- 2.5 mumol/g dry wt, P < .01) [1].
• Formation and utilization of novel high energy phosphate reservoirs in Ehrlich ascites tumor cells. Cyclocreatine-3-P and creatine-P [2].
• The results can be summarized as follow: (a) In the normoxic brain, the ratio between PCr and Pi was greater than 1 (1.2-1.4), while under hypoxia or asphyxia a significant decrease that was correlated to the FiO2 levels was recorded [3].
• Using results from both methods, at 20 degrees C the ratio of phosphorylcreatine split during a tetanus to O2 consumption during recovery ranged from 5.2 to 6.2 mumol/mumol, and postcontractile ATP hydrolysis was estimated to be 13.6 +/- 4.1 (n = 3) nmol/mumol total creatine [4].
• Finally, in the presence of 100 microM MgATP and 250 microM MgADP, a decrease in PCr resulted in rigor; the half-maximal contracture being recorded at 1 mM PCr [5].

High impact information on phosphocreatine

• We have blocked creatine kinase (CK)-mediated phosphocreatine (PCr) -->/<-- ATP transphosphorylation in skeletal muscle by combining targeted mutations in the genes encoding mitochondrial and cytosolic CK in mice [6].
• Metabolite channeling: a phosphorylcreatine shuttle to mediate high energy phosphate transport between sperm mitochondrion and tail [7].
• The finding of an isoenzyme of creatine phosphokinase attached to the M-line region of the myofibril revealed the peripheral receptor for the mitochondrially generated phosphorylcreatine [8].
• In group 4, hypoperfusion resulted in progressive damage. pH fell to 6.2 +/- 0.7, diastolic pressure increased to 34 +/- 5.6 mm Hg, CP and ATP became depressed, and oxidative stress occurred [1].
• After 45 min of reperfusion PCr recovered to 65 +/- 5% of control in untreated (group I) hearts compared with 89 +/- 8% in h-SOD-treated (group II) hearts (p less than .01 vs group I) and with 83 +/- 6% of control in h-SOD/catalase-treated (group III) hearts (p less than .05 vs group I) [9].

Chemical compound and disease context of phosphocreatine

• Myocardial ATP and phosphocreatine (PCr) content and intracellular pH during ischemia and reperfusion were continuously monitored with 31P nuclear magnetic resonance (NMR) spectroscopy [9].
• Myocardial creatine phosphate (CP) content was depleted after 15 min of ischemia in the untreated hearts, and after 20 min of ischemia in the hearts treated with nifedipine [10].
• The relative recovery of the PCr of the adult slices after aglycaemic hypoxia was the same with either 3HB or glucose [11].
• During reoxygenation after anoxia, concentrations of ATP and P-creatine rapidly recovered in slices preincubated with creatine [12].
• Decreases and oscillations in the [ATP]/[free ADP] ratio cannot be buffered effectively late in ischemia by the creatine-P system for thermodynamic reasons, or by the homocyclocreatine-P system because of kinetic limitations [13].

Biological context of phosphocreatine

• Doubling of the heart rate resulted in a significant decrease in phosphocreatine (PCr) content (11% at 28 degrees C, 8% at 37 degrees C), which was matched by an increase in inorganic phosphate (P(i)) content, although oxygen supply was shown to be nonlimiting [14].
• Because a possible involvement of energy metabolism in the action of ADM was suggested previously, the adenylate energy charge and phosphorylcreatine mol fraction were determined in the ADM-treated cells [15].
• A biochemical pathway for a cellular behaviour: pHi, phosphorylcreatine shuttles, and sperm motility [16].
• These properties enable cyclocreatine-P to continue to thermodynamically buffer the adenylate system and transport high energy phosphate throughout the long muscle fibers at cytosolic pH values and phosphorylation potentials well below the range where the creatine-P system can function effectively [17].
• Neither gestational age nor maternal diabetes affected the tissue's energy potential (ATP-to-ADP and PCr-to-Cr ratios) [18].

Anatomical context of phosphocreatine

• The subcellular fluxes of exchange of ATP and phosphocreatine (PCr) between mitochondria, cytosol, and ATPases were assessed by (31)P NMR spectroscopy to investigate the pathways of energy transfer in a steady state beating heart [19].
• Our results show that neural information, or the consequences of it, is required to maintain the levels and rates of synthesis of glycolytic enzymes but not of creatine-P kinase in mature fast-twitch muscle fibers [20].
• There was a gradient in ATP and P-creatine levels in dark-adapted retinas, with the lower concentrations in the photoreceptors, and increasing concentrations in the inner retina [21].
• In frozen-cut and dried sections taken from brains 3 days after freeze lesioning, discrete pieces of the median and lateral parietal cortex, striatum, hippocampus, and hypothalamus were dissected and analyzed for ATP, P-creatine, glucose, and lactate [22].
• 1. The role of phosphorylcreatine (PCr) and creatine (Cr) in the regulation of mitochondrial respiration was investigated in permeabilised fibre bundles prepared from human vastus lateralis muscle [23].

Associations of phosphocreatine with other chemical compounds

• Acetyl-P, ATP, enolpyruvate-P, creatine-P, and fructose-1,6-P2 are not phosphoryl donors [24].
• (b) A clear correlation was found between the decrease in PCr/Pi values and the increased NADH redox state developed under decreased O2 supply to the brain [3].
• In contrast with the untreated hearts, the nifedipine-treated hearts showed a rapid recovery of CP content during reperfusion [10].
• The in vivo redox status of cytochromes at different FiO2 was directly compared with in vitro measured changes in cortical metabolites known to reflect energy production, i.e., glucose, pyruvate, lactate, phosphocreatine (PCr), ADP, and ATP [25].
• This explanation is based on the slow diffusion of Mg2+ within the myofibril and on the contrast of PCr with both ATP and phosphoenolpyruvate, in that PCr does not bind Mg2+ under physiological conditions, whereas both the other two bind it more tightly than the products of their hydrolysis do [26].

Gene context of phosphocreatine

• CONCLUSION: PCr accumulation may prevent TNFalpha-induced apoptosis in murine hepatocytes by suppression of truncated Bid targeting to mitochondria [27].
• In M-CK-deficient muscles there was respective depletion of PCr, Cr and ATP levels to 31, 41 and 83% of normal [28].
• The effects of La infusion on intracellular [PCr], [Pi], [phosphomonoester], [ADP], and [NH3] in PFK-deficient patients are consistent with the hypothesis that exogenous La augments the rate of oxidative phosphorylation in active muscle by bypassing the enzymatic block at PFK [29].
• In contrast, the P-creatine and ATP decreased in the CA1 region at 48 and 96 hr of reflow, respectively [30].
• To determine if this reduction was merely the result of an ATP maintenance system, ATP was regenerated using either phosphoenolpyruvate and pyruvate kinase (PEP-PK), or PCr and soluble bovine cardiac CK [31].

Analytical, diagnostic and therapeutic context of phosphocreatine

• In contrast, denervation for as long as 6 weeks did not have a significant effect on the levels of creatine-P kinase molecules in this muscle type [20].
• The best correlations were found between EEG activity and pH and PCr; correlation coefficients ranged from 0.93 to 0.95 [32].
• Cr uptake was assessed by skeletal muscle (14)C-Cr accumulation to Cr and PCr by using hindlimb perfusion, and CrT protein content was assessed by Western blot [33].
• ATP, ADP, AMP, IMP, and PCr were determined by HPLC with UV detection in controls after maximal and endurance training for 6 weeks with or without a respective final test and also after final exhaustive or endurance test without preceding training [34].
• The levels of ATP and creatine phosphate (CP) at the site of MBF determination were measured 60 min after ligation, and mitochondrial function (RCI, QO2) in the ischemic and non-ischemic areas was determined [35].

References