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At least 19 recordsLinked to original sources
PubMed2001

In vivo monitoring of intracellular ATP levels in Leishmania donovani promastigotes as a rapid method to screen drugs targeting bioenergetic metabolism.

A method for the rapid screening of drugs targeting the bioenergetic metabolism of Leishmania spp. was developed. The system is based on the monitoring of changes in the intracellular ATP levels of Leishmania donovani promastigotes that occur in vivo, as assessed by the luminescence produced by parasites transfected with a cytoplasmic form of Phothinus pyralis luciferase and incubated with free-membrane permeable D-luciferin analogue D-luciferin-[1-(4,5-dimethoxy-2-nitrophenyl) ethyl ester]. A significant correlation was obtained between the rapid inhibition of luminescence with parasite proliferation and the dissipation of changes in mitochondrial membrane potential (DeltaPsi(m)) produced by buparvaquone or plumbagin, two leishmanicidal inhibitors of oxidative phosphorylation. To further validate this test, a screen of 14 standard leishmanicidal drugs, using a 50 microM cutoff, was carried out. Despite its semiquantitative properties and restriction to the promastigote stage, this test compares favorably with other bioenergetic parameters with respect to time and cell number requirements for the screening of drugs that affect mitochondrial activity.

Adenosine Triphosphate↗
PubMedDate not supplied

[Effect of impulse infrared laser radiation on bioenergetic metabolism in gastric mucosa in patients with gastroduodenal ulcer].

Gastric mucosa and blood plasm were studied in 82 patients with gastroduodenal ulcer for content of adenylic nucleotides (AMP, ADP and ATP), histamine, amino acids. It was found that the above nucleotides occurred in the examinees in subnormal quantities. The necessary substrates, aspartate in particular, were deficient. This may lead to impairment of biosynthetic processes, to imbalance of defense factors. Photon therapy of gastroduodenal ulcer corrects bioenergetic metabolism in gastric mucosa thus producing a marked therapeutic effect.

Adolescent↗
PubMed2006

Cardiac system bioenergetics: metabolic basis of the Frank-Starling law.

The fundamental principle of cardiac behaviour is described by the Frank-Starling law relating force of contraction during systole with end-diastolic volume. While both work and respiration rates increase linearly with imposed load, the basis of mechano-energetic coupling in heart muscle has remained a long-standing enigma. Here, we highlight advances made in understanding of complex cellular and molecular mechanisms that orchestrate coupling of mitochondrial oxidative phosphorylation with ATP utilization for muscle contraction. Cardiac system bioenergetics critically depends on an interrelated metabolic infrastructure regulating mitochondrial respiration and energy fluxes throughout cellular compartments. The data reviewed indicate the significance of two interrelated systems regulating mitochondrial respiration and energy fluxes in cells: (1) the creatine kinase, adenylate kinase and glycolytic pathways that communicate flux changes generated by cellular ATPases within structurally organized enzymatic modules and networks; and (2) a secondary system based on mitochondrial participation in cellular calcium cycle, which adjusts substrate oxidation and energy-transducing processes to meet increasing cellular energy demands. By conveying energetic signals to metabolic sensors, coupled phosphotransfer reactions provide a high-fidelity regulation of the excitation-contraction cycle. Such integration of energetics with calcium signalling systems provides the basis for 'metabolic pacing', synchronizing the cellular electrical and mechanical activities with energy supply processes.

Adenosine Triphosphate↗
PubMed1975

Restoration of myocardial bioenergetic metabolism in swine after periods of ischemic ventricular fibrillation.

Myocardial mitochondrial function and high energy phosphate levels were measured in normal swine, in swine after either 5 or 10 minutes of ischemic ventricular fibrillation (IVF) while on cardiopulmonary bypass, and in swine defibrillated after either 5 or 10 minutes of IVE. The damage to myocardial mitochondria induced by IVF, such as partial uncoupling, decreased oxygen uptake, and loss of cytochrome oxidase activity, was completely reversed almost instantly by coronary artery perfusion and the restoration of sinus rhythm. After either 5 or 10 minutes of IVF followed by coronary artery reperfusion and defibrillation, myocardial creatine phosphate (CP), adenosine monophosphate (AMP) and adenosine diphosphate (ADP) return to normal levels very rapidly. However, adenosine triphosphate (ATP) levels remain significantly lower than control levels. If the bioenergetic mechanisms of swine and human myocardium are similar, it appears that IVF at least for a 10 minute period produces no damage to myocardial mitochondria that is not corrected by perfusion of the coronary arteries and re-establishment of sinus rhythm. Furthermore, sinus rhythm can be re-established and maintained despite signficantly lower levels of myocardial ATP.

Adenine Nucleotides↗
PubMed1995

Blood flow of the urinary bladder: effects of outlet obstruction and correlation with bioenergetic metabolism.

This study investigated the effects of outlet obstruction on blood flow and high energy phosphates content in the rabbit urinary bladder. Mild bladder outlet obstruction was induced by placing a silicon ring (diameter 7 mm) around the bladder neck of each male New Zealand White rabbit (n = 7). Before and immediately after inducing obstruction, and 2 weeks later, the bladders were emptied and regional blood flow measured using laser Doppler flowmetry (LASERFLO BPM2, Vasamedics Inc., St. Paul, Minnesota). Six different areas of each bladder were measured, and the average blood flow calculated for each rabbit. Then, the animals were sacrificed, the bladder excised, and the tissue content of high energy phosphates determined by high performance liquid chromatography (HPLC). Six normal male New Zealand White rabbits served as controls. The results can be summarized as follows: (1) Before surgery, bladder blood flow was similar in all animals (16.3 ml/min/100 g); positioning the silicon ring around the bladder neck did not affect blood perfusion, two weeks after the induction of outlet obstruction, bladder blood flow was significantly decreased (4.9 ml/min/100 g). (2) There was no significant difference between control and obstructed bladders in NAD, AMP, or ADP content. However, the obstructed bladders contained significantly less phosphocreatine (12.0 vs 21.9 nmol/mg protein) and ATP (4.0 vs. 6.1 nmol/mg protein) than control bladders. In summary, this study showed that urinary bladder blood flow was reduced by outlet obstruction, and the reduction in blood flow was associated with decreased tissue high energy phosphates content.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1988

Oxygen tension within the arterial wall: relationship to altered bioenergetic metabolism and lipid accumulation.

Oxygen tension (pO2) was measured in upper thoracic arteries and in muscular foci at the celiac bifurcation from atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons at 6, 12, and 24 weeks of age. At each site the pO2 was measured within adventitial (outer), medial (middle), and subendothelial (inner) zones with polarographic oxygen microelectrodes while the animals were under dissociative anesthesia. The atherosclerosis-resistant Show Racer pigeons exhibited no significant age or site differences in pO2 levels. The medial pO2 was approximately 25 mm Hg, while the adventitial and subendothelial zones had pO2 levels of approximately 30 mm Hg. The pO2 profiles through the various zones of the arterial wall of 6-week-old atherosclerosis-susceptible White Carneau pigeons were similar to those of the Show Racers. However, significantly lower oxygen tension was found in the subendothelial zone from 12- and 24-week White Carneau celiac bifurcations (27 and 21 mm Hg) than in corresponding zones in Show Racer sites. Also, the medial zone in 24-week White Carneau celiac foci exhibited a significantly lower pO2 (20 mm Hg) than the medial zone of younger White Carneau. When correlated with previously described biochemical and morphological changes in White Carneau pigeons, the findings presented herein indicate that focal decreases in oxygen availability within arterial tissue occur after the onset of spontaneous atherogenesis, and probably result from decreased diffusion of oxygen into the arterial wall.

Animals↗
PubMed1980

Focal differences in bioenergetic metabolism of atherosclerosis-susceptible and -resistant pigeon aortas.

To test the hypothesis of altered energy production in aortic sites predisposed to lesion formation, both coupled oxidative phosphorylation (evaluated from P/O ratios) and control of the energy-linked (ATP) NADH transhydrogenase were examined in muscular cushions at the celiac artery bifurcation. Comparisons were made between atherosclerosis-susceptible White Carneau (WC) and atherosclerosis-resistant Show Racer (SR) pigeons at ages up to early atherogenesis in WC (1 day to 6 months of development). From 1 day to 12 weeks of age, mitochondria from cushions of both breeds tightly coupled phosphorylation to the oxidation of either beta-hydroxybutyrate or succinate. However, by 6 months of age, WC celiac cushions had significantly (P less than 0.05) lower P/O ratios than the SR cushions with either substrate, suggesting uncoupled respiratory-chain phosphorylation. Aortic submitochondrial A-particles from celiac cushions of susceptible pigeons showed no ATP regulation of NADH transhydrogenation at 6 weeks and subsequent ages. This defect is believed to enhance lipid biosynthesis and may be involved in exacerbation of the biochemical arteriopathy in WC. These findings are discussed in terms of relationships between oxidative energy production, lipid accumulation, hypoxic stress, and atherosclerotic involvement.

Adenosine Triphosphate↗
PubMed2003

[The influence of some trace elements on bioaccumulation in tissues and bioenergetic metabolism of the edible snail Helix aspersa maxima as determined by HPLC of purine derivatives].

UNLABELLED: The aim of this work was to determine the bioaccumulation of fluoride and some metals (Cu, Zn, Pb) in tissues of snails under strictly controlled conditions expecting with this approach to verify the hypothesis that snails are suitable for the monitoring of environmental hazards. Additionally, the toxicity of fluorides administered orally on the energy balance of the snail's foot was investigated basing on concentrations of nucleosides, nucleotides and their products measured with high-performance liquid chromatography (HPLC). Two parallel snail cultures were started. The effect of dose on tissue levels of fluoride and metals was studied in the first part of the experiment. The second part served to study the effects of fluoride on energy metabolism of foot muscle (Tab. 1). Quantitation of fluoride and metal levels was done in soft tissues (foot, hepatopancreas) and shells of snails. Qualitative and quantitative analysis of purine compounds was performed in slices of foot. Fluoride concentrations in pulverized shells were measured using an ion-selective electrode. Gas chromatography served to determine fluoride concentrations in soft tissues (hepatopancreas and foot). Concentrations of metals were determined spectrophotometrically. Fluoride and metal content was calculated basing on weight of the pulverized sample. Purines were measured in foot muscle slices with high-performance liquid chromatography (HPLC). Concentrations were adjusted for protein content of sample. Concentrations of the following nucleosides, nucleotides and their products were determined: ATP, ADP, AMP, Ado (adenosine), GTP, GDP, GMP, Guo (guanosine), Hyp (hypoxanthine), IMP, Ino (inosine), Xan (xanthine), Urd (uridine), UA (uric acid), NAD+, and NADP (Fig. 1.). Statistical analysis was done with non-parametric test of Kruskal-Wallis, Mann-Whitney U-test and Spearman Rank Correlation Coefficient. CONCLUSIONS: 1. Accumulation in the shell was significantly increased at the lowest concentration of fluoride, but levels remained below those in the foot or hepatopancreas. It can be inferred that due to low sensitivity, accumulation of fluoride in soft tissues is not a suitable indicator for biomonitoring purposes. Shells seem to be more suited for this aim. 2. Due to low sensitivity, accumulation of metals in soft tissues is not a suitable indicator for biomonitoring purposes. 3. Fluoride had a statistically significant effect on the energy metabolism in muscle, especially on the content of AMP and GMP (Fig. 3, 4). The content of adenylate derivatives was increased (Fig. 3, 4) and phosphorylation of ADP to ATP was inhibited (Fig. 2, 5). 4. An increase in TAN and AEC with 1330 mg F-/kg seems to result from inhibition by fluoride of energy-consuming processes (Fig. 5). 5. In cases of high levels of fluoride it seems reasonable to measure the content of AMP, GMP, Guo or the value of AEC which appear to serve as universal indicators of depressed metabolic function (Fig. 3, 4, 5, 6).

Adenosine Diphosphate↗
PubMed1989

[Prognostically significant indices of the bioenergetic metabolism of the brain in experimental ischemia (a NMR spectroscopic study)].

Initial levels of phosphate brain metabolites were measured using 31P NMR spectroscopy in rats which subsequently died or survived under bilateral ligation of common carotid arteries. A multidimensional analysis was applied. In the rats which died after the brain ischemia: (1), NAD and NADH+ concentrations were much higher than those of creatine phosphate or ATP (i.e. baseline dysbalance existed between the systems of hydrogen acceptors and major macroergic substances); (2), the force of relationships between parameters of NMR spectra in each correlation matrix were 10 times higher and the variability of elements in each matrix was significantly lower than those of the surviving group. These regularities can be used in detection of special groups at high professional risk and in designing individual procedures of prevention and treatment of cerebral circulation disorders. The data are valuable in terms of development of drugs which would correct the dysbalance between hydrogen acceptors and macroergic systems thus providing a metabolic defense for the ischemic brain.

Animals↗
PubMed1998

Analysis of muscle bioenergetic metabolism in rabbit leg lengthening.

The effect of lengthening on muscle metabolism was measured and correlated to the percent lengthening at early and late time points. Using the rabbit tibial lengthening model, the authors examined the effects of lengthening on the tibialis anterior muscle using phosphorus-31 magnetic resonance spectroscopy. Thirty-six rabbits were divided into five groups, four groups by percent lengthening (0%, 15%, 20%, and 25%), with each group divided into subgroups of early (end distraction) and late (12 weeks after end distraction), and the fifth group using the opposite untreated leg as control. Several parameters measuring metabolism of muscle using phosphorus-31 magnetic resonance spectroscopy analysis were compared. No changes occurred to 15% lengthening, but significant decreases were measured at 20% and 25% lengthening. After a 25% lengthening, the decreased metabolism persisted at 12 weeks after distraction, indicating the possibility of permanent damage. After 20% lengthening, the same parameters improved but never to normal levels. The authors conclude that lengthening to 15% is safe for muscle, but 20% to 25% lengthening may result in permanent metabolic damage. The current study also suggests that phosphorus-31 magnetic resonance spectroscopy may provide a viable clinical method for evaluating muscle damage during lengthening.

Adenosine Triphosphate↗
PubMed1999

Quantitative changes of metabolic and bioenergetic parameters in experimental tumors during fractionated irradiation.

PURPOSE: Previous studies with rat rhabdomyosarcomas indicate that during fractionated irradiation profound alterations of the tumor microvasculature and the oxygenation status occur when the total dose exceeds 45 Gy. At this dose a destruction which included all structures of the vessels and a significant worsening in tumor oxygenation were found. The aim of the present study was to analyze whether these effects of fractionated irradiation on the microvasculature and on tumor oxygenation also induce changes in the bioenergetic and metabolic status in the tumors during radiation treatment. METHODS AND MATERIALS: R1H rhabdomyosarcomas of the rat implanted into the flank were irradiated with 60Co-gamma-rays using 5 fractions of 3 Gy per week over 5 weeks. During this irradiation schedule, tumors were investigated each week for the microregional distributions of glucose, lactate, and ATP concentrations. For this, tumors were rapidly excised, shock-frozen and quantitative bioluminescence measurements were performed on tumor tissue sections. RESULTS: ATP concentrations remained unchanged during fractionated irradiation up to a total dose of 45 Gy. Above this dose, a significant decrease in ATP levels was observed. Lactate concentrations changed only slightly during irradiation whereas glucose levels increased continuously over the whole irradiation period. CONCLUSIONS: During fractionated irradiation of R1H tumors with a total dose of 75 Gy, the bioenergetic and metabolic status of the tumors changed considerably. This became most obvious once a dose of 45 Gy had been achieved. The severe energy depletion and worsening of tumor oxygenation might be the result of destruction of tumor blood vessels as has been described previously in the same tumor model. The modification of the tumor micromilieu appears to be an important parameter in the responsiveness of tumor cells to radiation and for local tumor control.

Adenosine Triphosphate↗
PubMed1988

Continuous nasoenteric feeding: bioenergetic and metabolic response during recovery from semistarvation.

The bioenergetic and metabolic response to continuous nasoenteric feeding was examined under balance conditions for up to 22 d in 12 stable undernourished medical patients. Each subject received a fixed inflow of the mixed-fuel formula at rates of one to three times maintenance energy requirement. The pooled results were used to develop a composite profile of physiologic changes during recovery from semistarvation. Body weight, whole-body gas exchange, minute ventilation, thermal and chemical energy losses, and balances of energy, nitrogen, potassium, and sodium changed as a function of formula infusion rate and duration of feeding. These component measurements allowed calculation of such classic bioenergetic efficiency terms as digestible, metabolizable, and net energy as functions of infused energy (IE, kcal.kg fat free body mass-1.h-1: 0.96IE, 0.93IE, and 6.7 [1 - e-0.16IE], respectively) and the energy content of weight gain (means +/- SD; early, 4.2 +/- 3.5 kcal/g, and later, 7.4 +/- 3.6 kcal/g). Continuous nasoenteric feeding provides a unique opportunity to define previously unexplored dietary and metabolic interrelations in humans.

Adult↗
PubMed1983

[Methodologic studies on protein metabolism and bioenergetics of protein deposition in growing animals. 4. Energy metabolism in chickens in connection with measurement of parameters of protein metabolism].

In connection with the measuring of parameters of the protein metabolism in parallel experiments, the energy metabolism of 6 chickens (origin Tetra B) in the live weight range between approximately 100 and 1,800 g was determined under conditions of restricted energy supply. 3 animals each received a feed mixture containing 20% (animal group 1) and 38% (animal group 2) crude protein. The amount of feed was daily increased by 1.5 g DM. The digestibility of energy and nitrogen was independent of the age. 66.3 +/- 3.3% and 64.0 +/- 5.0% resp. of the metabolisable energy were utilised for protein and fat retention. The energy maintenance requirement, determined at a live weight of 2,000 g, was independent of protein supply and averaged in the two animal groups 434 +/- 40 kJ metabolisable energy/kg live weight 0.75 . d. The result of multiple regression was, for the growth period investigated, an energy maintenance requirement of 403 +/- 32 kJ metabolisable energy/kg live weight 0.75 . d. 1.77 and 1.38 J metabolisable energy resp. were required for 1 J protein or fat retention. The energy requirement for protein retention was independent of the degree of protein supply. The results from the measuring of energy metabolism are discussed in connection with the kinetic parameters of protein metabolism ascertained in parallel experiments.

Animals↗
PubMed2004

The role of ribose in human skeletal muscle metabolism.

Bioenergetic pathways in muscle provide high-energy compounds that are required for cellular integrity and function. Increased cellular demand for adenosine triphosphate (ATP) or limitations in the rephosphorylation rate of adenosine diphosphate (ADP) can decrease the total adenine nucleotide (TAN) pool, which may take several days to recover or may not recover at all in cases of chronic ischemia. Total adenine nucleotide levels may be significantly decreased as a result of myocardial or skeletal muscle ischemia, certain metabolic diseases, repeated intense skeletal muscle contractions or in repetitive high-intensity exercise. Ribose, a naturally occurring pentose sugar, has been shown to enhance the recovery of myocardial or skeletal muscle ATP and TAN levels following ischemia or high-intensity exercise. Furthermore, ribose has been demonstrated to modulate the production of oxygen free radicals during and following exercise. The following paper reviews skeletal muscle energetics and the potential role of ribose during and following exercise.

Adenosine Triphosphate↗
PubMed2004

Brain gene expression, metabolism, and bioenergetics: interrelationships in murine models of cerebral and noncerebral malaria.

Malaria infection can cause cerebral symptoms without parasite invasion of brain tissue. We examined the relationships between brain biochemistry, bioenergetics, and gene expression in murine models of cerebral (Plasmodium berghei ANKA) and noncerebral (P. berghei K173) malaria using multinuclear NMR spectroscopy, neuropharmacological approaches, and real-time RT-PCR. In cerebral malaria caused by P. berghei ANKA infection, we found biochemical changes consistent with increased glutamatergic activity and decreased flux through the Krebs cycle, followed by increased production of the hypoxia markers lactate and alanine. This was accompanied by compromised brain bioenergetics. There were few significant changes in expression of mRNA for metabolic enzymes or transporters or in the rate of transport of glutamate or glucose. However, in keeping with a role for endogenous cytokines in malaria cerebral pathology, there was significant up-regulation of mRNAs for TNF-alpha, interferon-gamma, and lymphotoxin. These changes are consistent with a state of cytopathic hypoxia. By contrast, in P. berghei K173 infection the brain showed increased metabolic rate, with no deleterious effect on bioenergetics. This was accompanied by mild up-regulation of expression of metabolic enzymes. These changes are consistent with benign hypermetabolism whose cause remains a subject of speculation.

Animals↗
PubMed1994

Excess membrane cholesterol is not responsible for metabolic and bioenergetic changes in AS-30D hepatoma mitochondria.

Using mitochondria isolated from normal rat liver and AS-30D hepatoma in addition to cholesterol-enriched mitochondria, we have evaluated the ability of membrane cholesterol to induce changes in mitochondrial function, specifically, the preferential export of citrate (i.e., truncation of the Krebs cycle). Two in vitro cholesterol-enrichment procedures failed to produce mitochondria with any physiologically significant increases in free membrane cholesterol. Alternatively, male Wistar rats were maintained on a 2% cholesterol diet to elevate mitochondrial cholesterol. This treatment resulted in liver mitochondria which contained 70% of the cholesterol levels found in AS-30D hepatoma mitochondria, yet only minor metabolic and bioenergetic alterations. Subfractionation of the various mitochondrial preparations revealed that cholesterol was located primarily in outer membranes of both the cholesterol-enriched and AS-30D preparations. We therefore conclude that an increase in membrane cholesterol is not sufficient to induce "truncation" of the citric acid cycle or any other mitochondrial abnormality in tumor cells.

Animals↗