Disease relevance of Creatine phosphate

• In animals, severe myocardial ischemia is characterized by the rapid loss of phosphocreatine and a decrease in the ratio of phosphocreatine to ATP [1].
• The mean (+/- SD) ratio of phosphocreatine to ATP in the left ventricular wall when subjects were at rest was 1.72 +/- 0.15 in normal subjects (n = 11) and 1.59 +/- 0.31 in patients with nonischemic heart disease (n = 9), and the ratio did not change during hand-grip exercise in either group [1].
• Adenosine (n = 10, mean dose 0.16 mg/kg-min) increased RV blood flow by an additional 41% without increasing PCr/ATP, indicating that coronary reserve was not depleted and that the decrease in PCr/ATP from control was not due to ischemia [2].
• Sheep undergoing graded hypoxia (n = 5) with an arterial PO2 nadir of 13.4 +/- 0.5 mmHg, demonstrated maintained rates of oxygen consumption with large changes in coronary flow as phosphocreatine (PCr) decreased within 4 min to 40 +/- 7% of baseline [3].
• Collection of 31P NMR spectra from hearts of renal failure and control animals during 30 min normoxic Langendorff perfusion showed that basal phosphocreatine was reduced by 32% to 4.7 mumol/g wet wt (P < 0.01) and the phosphocreatine to ATP ratio was reduced by 32% (P < 0.01) in uremic hearts [4].

Psychiatry related information on Creatine phosphate

• OBJECTIVE: To assess the effects of age and dementia on gray matter and white matter concentrations of 3 metabolites visible in the proton spectrum: N-acetyl compounds, present only in living neurons; creatine plus phosphocreatine, reflecting high-energy phosphate metabolism; and choline, increasing with membrane synthesis and degradation [5].
• Creatine, which increases muscle and brain phosphocreatine concentrations, and may inhibit the activation of the mitochondrial permeability transition, protects against neuronal degeneration in transgenic murine models of amyotrophic lateral sclerosis and Huntington's disease and in chemically mediated neurotoxicity [6].
• The concentration of creatine and phosphocreatine, metabolites involved in energy-dependent systems in brain, was significantly lower in the right medial temporal lobe region of panic disorder patients compared to healthy subjects [7].
• Moreover, significant negative correlations were noted between total Brief Psychiatric Rating Scale scores and PCr/beta-ATP in both the right and left temporal lobes [8].
• RESULTS: A significant reduction in N-acetyl-aspartate/choline and N-acetyl-aspartate/(creatine/phosphocreatine + choline) was observed in both the right and left medial thalami in obsessive-compulsive disorder patients compared with control subjects [9].

High impact information on Creatine phosphate

• The decrease in the ratio of phosphocreatine to ATP during hand-grip exercise in patients with myocardial ischemia reflects a transient imbalance between oxygen supply and demand in myocardium with compromised blood flow [1].
• Mib-CK consumes ATP produced in the mitochondria for the production of phosphocreatine, which is then exported into the cytosol for fast regeneration of ATP by the cytosolic CK isoforms [10].
• Creatine kinase (CK, EC 2.7.3.2), an enzyme important for energy metabolism in cells of high and fluctuating energy requirements, catalyses the reversible transfer of a phosphoryl goup from phosphocreatine to ADP [10].
• We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle [11].
• Second, under baseline conditions alphaMHC403/+ hearts had lower phosphocreatine and increased inorganic phosphate contents resulting in a decrease in the calculated value for the free energy released from ATP hydrolysis [12].

Chemical compound and disease context of Creatine phosphate

• CONCLUSIONS: Metabolic markers of ischemia such as ratio of phosphocreatine to ATP, ATP content, lactate content, and lactate production were blunted during this protocol of gradually worsening ischemia [13].
• After 1 h of ischemia intracellular pH was 6.73 +/- 0.06, PCr/ATP was decreased by 77 +/- 8%, whereas PArg/ATP was decreased by 50 +/- 15% of basal levels [14].
• Furthermore, in CHF hearts, the low basal PCr/ATP and the attenuated response to dobutamine occurred in the absence of myocardial hypoxia, indicating that the HEP and contractile abnormalities were not the result of insufficient oxygen availability [15].
• Hearts treated with deferoxamine during ischemia showed better recovery of developed pressure than did control hearts (63.2 +/- 7.5% versus 41.2 +/- 2.9% of baseline) (p = 0.02) and better recovery of myocardial phosphocreatine content (92.4 +/- 10.3% versus 68.2 +/- 4.5% of baseline, p less than 0.05) [16].
• This contractile profile was accompanied by a persistent increase in oxygen consumption, a monotonic decline in cellular adenosine triphosphate and phosphocreatine content, the development of marked intracellular acidosis, a gain in cell sodium and calcium content, and a reduction in cell potassium [17].

Biological context of Creatine phosphate

• Thus: (a) The decline in PCr/ATP with moderate RV pressure overload, without evident ischemia or contractile dysfunction, supports the positive regulation of oxidative phosphorylation by ATP hydrolysis products [2].
• During muscle contraction hydrolysis of ATP results in an increase in phosphorus, free ADP, delta GATP, and a reduction in phosphocreatine levels that is reversed during rest by rephosphorylation of ADP to ATP and the resynthesis of phosphocreatine by ATP [18].
• The goal of these experiments was to investigate the relationship of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), monobasic phosphate (H2PO4-), and pH to human muscle fatigue [19].
• CONCLUSIONS: Abundant phosphocreatine promotes liver regeneration by reinforced hepatic energy metabolism [20].
• At a constant phosphocreatine concentration (5 mmol/L, pH 7.1), the relation of sliding velocity to MgATP concentration followed Michaelis-Menten kinetics [21].

Anatomical context of Creatine phosphate

• Changes in phosphocreatine, ATP, and intracellular pH in the gastrocnemius muscle were followed during a graded steady state exercise protocol, and the recovery of phosphocreatine was followed on cessation of exercise [22].
• Effect of acetylsalicylic acid on gastric mucosa. II. Mucosal ATP and phosphocreatine content, and salicylate effects on mitochondrial metabolism [23].
• The dissociated myocytes display Ca uptake and phasic contractions that are apparently dependent on mitochondrial respiration, but are not affected by mitochondrial uncouplers when ATP and phosphocreatine are added [24].
• DESIGN: Left prefrontal cortex and left mediotemporal lobe voxels were assessed using proton magnetic resonance spectroscopy to provide the ratio of N-acetylaspartate (NAA) and choline-containing compounds to creatine and phosphocreatine (Cr) (NAA/Cr ratio) [25].
• MAIN OUTCOME MEASURES: Magnetic resonance spectroscopy measures of N-acetylaspartate-creatine and phosphocreatine (NAA/Cr), choline-creatine and phosphocreatine (Cho/Cr), and choline-N-acetylaspartate (Cho/NAA) ratios were obtained in the anterior cingulate cortex as well as in the primary visual cortex, which served as a control region [26].

Associations of Creatine phosphate with other chemical compounds

• 31P nuclear magnetic resonance (NMR) spectroscopy in vivo and fluorometry were used to measure muscle ATP, total creatine, pH, and Mg2+ in vivo; and to calculate creatine phosphate (CrP), the ratios of CrP/inorganic phosphate (Pi), CrP/ATP, free ADP levels, and the free-energy change in ATP hydrolysis so nutritional effects could be ascertained [27].
• Dichloroacetate resulted in less lactate accumulation (10.3 +/- 3.0 vs 58.9 +/- 10.5 mmol.kg-1 dry muscle [dm], P < 0.05) and phosphocreatine hydrolysis (15.6 +/- 6.3 vs 33.8 +/- 9.0 mmol.kg-1 dm, P < 0.05) during contraction [28].
• Inorganic phosphate (Pi) and phosphocreatine (PCr) were monitored by magnetic resonance spectroscopy in both forearms at rest and during submaximal wrist flexion exercise at 6, 12, 24, and 36 J.min-1 before and after exercise training [29].
• Paired analysis showed that the phosphocreatine/inorganic-phosphate (PCr/Pi) ratio increased from a median of 2.04 (interquartile range 0.15) to 2.22 (0.25) after treatment with levothyroxine (p = 0.01) [30].
• MAIN OUTCOME MEASURES: Estimates of gray and white matter concentrations for choline-containing compounds (Cho), creatine plus phosphocreatine, N-acetylaspartate (NAA), and myo-inositol (mI) [31].

Gene context of Creatine phosphate

• The degree of reduction in the phosphocreatine concentration and phosphorylation potential and of increase in the inorganic phosphate concentration was, however, similar in the two groups with the 11778/ND4 mtDNA mutation with or without the haplogroup J [32].
• Similarly, the rate of muscle phosphocreatine resynthesis after exercise, a sensitive index of the rate of mitochondrial ATP production, was reduced by the same extent in both groups of LHON subjects [32].
• VIP (4.0 micrograms/100 g BW) caused a reduction in the high energy metabolite phosphocreatine and an increase in inorganic phosphate [33].
• To study the physiological role of the creatine kinase/phosphocreatine (CK/PCr) system in cells and tissues with a high and fluctuating energy demand we have concentrated on the site-directed inactivation of the B- and M-CK genes encoding the cytosolic CK protein subunits [34].
• The demonstration that phosphocreatine is used as an energy source by rat PRL-secreting pituitary tumours prompted the study of the enzyme creatine kinase in both rat and human pituitary tumours [35].

Analytical, diagnostic and therapeutic context of Creatine phosphate

• No differences in the effects of steady state exercise on muscle phosphocreatine levels were observed between the control group and the HIV-positive patients who had not been treated with AZT [22].
• Spatially localized 31P-NMR spectroscopy provided measurements of the transmural distribution of myocardial ATP, phosphocreatine (CP), and inorganic phosphate (Pi); spectra were calibrated from measurements of ATP content in myocardial biopsies using HPLC [36].
• During static hand-grip, there were no between-group differences in phosphocreatine (PCr), inorganic phosphate (Pi), or PCr/(PCr + Pi), although intracellular pH was higher in hemodialysis patients than transplant recipients [37].
• The aim of this study was to examine the energy energy metabolism and regeneration after hepatectomy using transgenic mouse liver expressing creatine kinase to clarify the effects of phosphocreatine on liver regeneration [20].
• Overshoot of Pcr (which indicates that the energy generating system is operating better than energy utilizing system) persisted in preconditioned hearts but disappeared rapidly in controls (control/preconditioned, 104 +/- 3%/130 +/- 3% after 120 minutes of reperfusion) [38].

References