Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hyperglycemia-induced in situ metabolism and blood flow changes produced in s.c. implanted murine radiation-induced fibrosarcoma-1 tumors, grown on the flanks of female C3H/HeJ mice, were examined with 31P and 2H nuclear magnetic resonance. Initial experiments verified a hyperglycemic tumor acidification similar to that reported earlier with a different substrain of mice, C3H/AnF (J.L. Evelhoch et al., Proc. Natl. Acad. Sci. USA, 81: 6496-6500, 1984). Changes in the tumor pH, phosphorus metabolites, and blood flow were then compared after administration of saline, glucose, or mannitol (a nonmetabolizable glucose analogue) using a mole-equivalent dose of the sugars (i.e., 0.8 mmol/20g mouse). Neither saline (n = 8) nor mannitol (n = 6) administration had any marked effect upon tumor pH, whereas glucose administration produced a mean maximum tumor pH reduction of 0.74 +/- 0.09 (SE; n = 9) during the 2.5 h post-glucose injection. No significant changes in high energy phosphate concentrations were observed during the same period after saline injection. After glucose injection, the [phosphocreatine] gradually decreased by 64% (P = 0.0001). After the initial 1 h post-glucose injection, the [inorganic phosphate] increased by 58% (P = 0.0001), and the [nucleoside triphosphates] decreased by 29% (P = 0.0001) during the following 1.5 h. After mannitol injection, while there was no change in [inorganic phosphate] over time (P = 0.37), the [phosphocreatine] decreased by 33% (P = 0.0001) and the [nucleoside triphosphates] decreased by 21% (P = 0.0015) within 20 min, then both the [phosphocreatine] and [nucleoside triphosphates] remained at constant levels during the following 2 h. In parallel experiments, the volumetric rate of tumor blood flow and perfusion was measured by 2H nuclear magnetic resonance monitoring of 2H2O washout kinetics (S-G. Kim and J. J. H. Ackerman, Cancer Res., 48: 3449-3453, 1988); tumor blood flow decreased by 80% (P = 0.0001, n = 11), 60% (P = 0.0031, n = 4), and 20% (P = 0.058, n = 10) at 2 h after glucose, mannitol, or saline injections, respectively. These results suggest that anaerobic glycolysis is a requirement for hyperglycemic tumor acidification. However, the decrease in tumor blood flow accompanying hyperglycemic acidification suggests that flow reduction also may be a contributing or a required cofactor for acidification via inhibition of lactic acid egress.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Modulation of murine radiation-induced fibrosarcoma-1 tumor metabolism and blood flow in situ via glucose and mannitol administration monitored by 31P and 2H nuclear magnetic resonance spectroscopy. 190 1

We measured brain energy phosphate metabolism and intracellular pH (pHi) in a cross-sectional study of migraine patients by in vivo phosphorus 31 NMR spectroscopy. During a migraine attack the ratio ATP/total phosphate signal (mole % ATP) was preserved, but there was a decrease in mole % phosphocreatine (PCr) and an increase in mole % inorganic phosphate (Pi) resulting in a decrease of the PCr/Pi ratio, an index of brain phosphorylation potential. This was found in classic but not common migraine. Mole % Pi was also increased in combined brain regions between attacks. There was no alteration in brain pHi during or between attacks. Energy phosphate metabolism but not pHi appears disordered during a migraine attack.
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PMID:Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 31 NMR spectroscopy. 292 79

Oxidized dialdehyde analogs of ADP or ATP (oADP and oATP) were shown to inhibit irreversibly adenine nucleotide translocator (T) and creatine kinase (CK) in heart mitochondria. Inactivation of T and CK was parallel with carboxyatractyloside - sensitive and (ADP + phosphocreatine) - sensitive incorporation of o[3H]ADP into mitochondria, respectively. o[3H]ADP incorporation sensitive to CAT or ADP+phosphocreatine was used to determine T and CK contents in mitochondria. T content in cardiac mitochondria from rat, rabbit, dog, and chicken was calculated to be 2.6 - 2.9 moles/mole cyt.aa3. The same value of T/cyt.aa3 ratio was found in liver mitochondria with lower cytochrome aa3 content. In all types of cardiac mitochondria CK content was found to be 2.4 - 2.6 moles/mole cyt.aa3. The data show that T and CK are present in molar ratio 1:1 in all types of cardiac mitochondria.
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PMID:Affinity modification of creatine kinase and ATP-ADP translocase in heart mitochondria: determination of their molar stoichiometry. 300 38

The interaction of mitochondrial creatine kinase and ATP-ADP translocase with 2.3-dialdehyde derivatives of ADP and ATP (oADP and oATP) has been studied. It was shown that these compounds are irreversible and specific inhibitors of creatine kinase (KioADP = 0.6mM, KioATP = 1.12 mM) and ATP-ADP translocase (KioADP = 0.065mM, KioATP = 0.14 mM). The substrates protect both enzymes from inactivation by these compounds. The maximal pseudo-first order rate constants for the 2,3-dialdehyde nucleotide derivative interaction with creatine kinase are 0.2 min-1 for oADP (pH 6.5) and 0.11 min-1 for oATP (pH 7.0). A decrease in the creatine kinase activity correlates with the incorporation of the reagent into the protein. The completely inactivated, isolated and purified enzyme contains 1 mol of oADP per mole of active sites. A procedure for simultaneous determination of the creatine kinase and translocase content in mitochondria and mitoplasts has been developed, which is based on the application of [3H]oADP in combination with specific treatment of mitochondria (or mitoplasts) with carboxyatractyloside 2,4-dinitrofluorobenzene and a mixture of creatine kinase substrates (MgADP + phosphocreatine). It has been found that for heart mitochondria from different animals the content of creatine kinase and translocase is 2.1-2.6 and 2.4-2.9 mol per mol of cytochrome c oxidase, respectively. Thus, the stoiochiometric ratio of creatine kinase and ATP-ADP translocase is close to 1.0 for all mitochondrial preparations under study (i.e. rat, dog, rabbit and chicken).
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PMID:[Affinity modification of creatine kinase and ATP-ADP translocase in heart mitochondria: determination of their stoichiometric ratio]. 302 Dec 43

The relation between metabolic and functional derangement in various cardiomyopathies has not been well characterized. This information was specifically sought in a spontaneous cardiomyopathic model. Metabolic and hemodynamic parameters were obtained in glucose-perfused beating hearts of 180-200-day-old cardiomyopathic Syrian hamsters and age-matched healthy animals. This period in the cardiomyopathic hamster lifetime is intermediary between the necrotic phase and the appearance of heart failure. We used 31P nuclear magnetic resonance spectroscopy to analyze energy metabolites and intracellular pH. Cardiomyopathic hamsters had significantly higher mole fraction values for inorganic phosphate, lower phosphocreatine mole fraction as well as lower phosphocreatine/inorganic phosphate and adenosine triphosphate/inorganic phosphate ratios. Analysis of pH indicated the presence of regions of increased acidity within the heart of myopathic hamsters. Cardiomyopathic hamsters also had significantly lower left ventricular pressure, coronary flow, and myocardial oxygen consumption. Separate groups of normal and myopathic hamsters were given verapamil for 24 hours (one injection of 4 mg/kg s.c. followed by 1.2 g/l in drinking water). Verapamil-treated myopathic hamsters had evidence of markedly improved mitochondrial function when compared with untreated animals. Left ventricular pressure and coronary flow rose to normal levels. Replacing glucose by pyruvate in the perfusate of myopathic hamsters results in a marked increase in left ventricular pressure, coronary flow, and oxygen consumption with a moderate rise in phosphocreatine. Thus, 180-200-day-old cardiomyopathic hamster heart is characterized by evidence of decreased mitochondrial function, by areas of increased acidity within the heart, and by reduced left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of the hereditary Syrian hamster cardiomyopathy by 31P nuclear magnetic resonance spectroscopy: improvement after acute verapamil therapy. 381 56

Tissues of chicks fed 5% N-methyl-3-guanidinopropionate (N-amidino-N-methyl-beta-alanine) for 12 days accumulated the following amounts of free plus phosphorylated derivatives as mumol/g, wet weight: brain, 5.5; heart, 7.3; leg muscle, 21.0; and breast muscle, 24.4. Since total creatine levels remained nearly the same in brain, N-methyl-3-guanidinopropionate-P provided brain with a supplemental reservoir of high energy phosphate. Tissues of rats fed 2% N-ethylguanidinoacetate (N-amidino-N-ethylglycine) accumulated large amounts of N-ethylguanidinoacetate-P, which has thermodynamic properties similar to creatine-P and is the kinetically most reactive synthetic phosphagen yet described. N-Ethylguanidinoacetate derivatives replaced creatine derivatives mole-for-mole, and the fraction of synthetic to total phosphagen after 19 days was 60% in heart, 54% in slow oxidative muscle, 42% in fast glycolytic muscles, and 22% in brain. N-Ethylguanidinoacetate served as a false end product co-repressor of liver arginine:glycine amidinotransferase levels in both chicks and chick embryos; N-methyl-3-guanidinopropionate and N-propylguanidinoacetate were relatively inactive. Creatinine amidohydrolase reversibly cyclized both N-ethylguanidinoacetate and N-propylguanidinoacetate with even lower Km values than for creatine derivatives, but it did not react significantly with N-methyl-3-guanidinopropionate, 3-guanidinopropionate, or 1-carboxy-methyl-2-imino-imidazolidine (cyclocreatine). Creatine amidinohydrolase also hydrolyzed N-acetimidoylsarcosine, but was relatively unreactive toward N-ethylguanidinoacetate, N-methyl-3-guanidinopropionate, 3-guanidinopropionate, and cyclocreatine. Amidinohydrolase can therefore be used to remove interfering creatine in assays of tissues for coexisting N-ethylguanidinoacetate or N-methyl-3-guanidinopropionate. Assays are now available to follow changes during metabolic stresses of any combination or all of the following phosphagens accumulated by the same tissue: creatine-P, N-ethylguanidinoacetate-P, cyclocreatine-P, N-methyl-3-guanidinopropionate-P, and homocyclocreatine-P.
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PMID:Higher homolog and N-ethyl analog of creatine as synthetic phosphagen precursors in brain, heart, and muscle, repressors of liver amidinotransferase, and substrates for creatine catabolic enzymes. 405 45

1. Changes in the concentrations of ATP, ADP, AMP, IMP, creatine and phosphorylcreatine (PC) have been measured in frog sartorius muscles after different periods of isometric stimulation at 20 degrees C. The heat production was measured in parallel experiments with a thermopile of the Hill-Downing type.2. Muscles were either in O(2) and unpoisoned or in N(2) and poisoned with iodoacetic acid to prevent aerobic and glycolytic recovery processes.3. Poisoning did not appear to alter the heat production of these muscles and had little effect on the tension for up to 8 sec tetanus.4. The break-down of high-energy phosphates ( approximately P) during contraction was faster in the poisoned muscles. Normal muscles were thus able to resynthesize high energy phosphates during the contraction. The resynthesis began at its maximum rate; part of it was probably due to glycolytic activity.5. During the first 2 sec of contraction (poisoned muscles), the only net reaction was an hydrolysis of PC, with an apparent enthalpy change of -8.3 kcal/mole. During longer contractions, the PC hydrolysis was accompanied by a net ATP hydrolysis and appearance of AMP and IMP.6. For the first 2 sec of contraction in the poisoned muscles, the observed heat agreed with that expected from the observed chemical changes multiplied by their molar enthalpy changes. After 2 sec, the observed heat was greater than that expected. At 12 sec this excess was about 74 mcal/g. Possible explanations for this discrepancy are discussed.
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PMID:Energy balance in frog sartorius muscle during an isometric tetanus at 20 degrees C. 475 78

1. Measurements have been made of heat production and changes in levels of phosphorylcreatine (PC), ATP and lactic acid resulting from contraction of tortoise muscle under anaerobic conditions.2. The only significant chemical change found was a break-down of PC.3. The amount of heat produced per mole of PC split (-DeltaH) was 13.18 +/- 1.04 kcal/mole (mean and S.E. from thirty-five observations).4. (-DeltaH) is probably rather greater in tortoise than in frog muscle. The value of (-DeltaH) cannot easily be accounted for by the known processes accompanying PC splitting in either type of muscle.
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PMID:Heat production and chemical change in tortoise muscle. 549 95

1. A new instrument, the integrating thermopile, is described for measuring the total quantity of heat produced during muscular contraction.2. This instrument has been used to investigate the relation between change of enthalpy (- (heat produced + work produced)) and break-down of phosphorylcreatine (DeltaPC) in iodoacetate-poisoned frog sartorii at 0 degrees C. In a variety of different types of contraction-series of isometric twitches, isometric tetani, contractions with positive and with negative work-the relation between enthalpy change and DeltaPC was always the same, and corresponded to an in vivo molar enthalpy change (DeltaH) of -11.0 +/- 0.23 (S.E.; n = 52) kcal/mole.3. This value of DeltaH is used to estimate the in vivo DeltaH for ATP splitting and also the number of rephosphorylations to be expected per hexose unit oxidized by normal unpoisoned muscle.
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PMID:Heat work and phosphorylcreatine break-down in muscle. 563 98

Recently Caplan (1) applied the concepts of irreversible thermodynamics and cybernetics to contracting muscle and derived Hill's force-velocity relation. Wilkie and Woledge (2) then compared Caplan's theory to chemical rates inferred from heat data and concluded that the theory was not consistent with the data. Caplan defended his theory in later papers (3, 4) but without any direct experimental verifications. As Wilkie and Woledge (2) point out, the rate of phosphorylcreatine (PC) breakdown during steady states of shortening has not been observed because of technical difficulties. In this paper it is shown that the rate equations may be directly integrated with time to obtain relations among actual quantities instead of rates. The validity of this integration is based on experimental evidence which indicates that certain combinations of the transport coefficients are constant with muscle length. These equations are then directly compared to experimental data of Cain, Infante, and Davies (5) with the following conclusions: (a) The measured variations of DeltaPC for isotonic contractions are almost exactly as predicted by Caplan's theory. (b) The value of the chemical rate ratio, nu(m)/nu(o), obtained from these data was 3.53 which is close to the value of 3 suggested by Caplan (3). (c) The maximum value of the chemical affinity for PC splitting was found to be 10.6 k cal/mole which is as expected from in vitro measurements (2). Because of the excellent agreement between theory and experiment, we conclude that Caplan's theory definitely warrants further investigation.
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PMID:Comparison of Caplan's irreversible thermodynamic theory of muscle contraction with chemical data. 578 14


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