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The energy production of mitochondria in heart increases during exercise. Several works have suggested that calcium acts at multiple control points to activate net ATP production in what is termed 'parallel activation'. To study this, a computational model of mitochondrial energy metabolism in the heart has been developed that integrates the Dudycha-Jafri model for the tricarboxylic acid cycle with the Magnus-Keizer model for mitochondrial energy metabolism and calcium dynamics. The model improves upon the previous formulation by including an updated formulation for calcium dynamics, and new descriptions of sodium, hydrogen, phosphate, and ATP balance. To this end, it incorporates new formulations for the calcium uniporter, sodium-calcium exchange, sodium-hydrogen exchange, the [F.sub.1][F.sub.0]-ATPase, and potassium-hydrogen exchange. The model simulates a wide range of experimental data, including steady-state and simulated pacing protocols. The model suggests that calcium is a potent activator of net ATP production and that as pacing increases energy production due to calcium goes up almost linearly. Furthermore, it suggests that during an extramitochondrial calcium transient, calcium entry and extrusion cause a transient depolarization that serve to increase NADH production by the tricarboxylic acid cycle and NADH consumption by the respiration driven proton pumps. The model suggests that activation of the [F.sub.1][F.sub.0]-ATPase by calcium is essential to increase ATP production. In mitochondria very close to the release sites, the depolarization is more severe causing a temporary loss of ATP production. However, due to the short duration of the depolarization the net ATP production is also increased. oxidative phosphorylation; tricarboxylic acid cycle; pH; computer model doi: 10.1152/ajpcell.00271.2006

Mitochondria have been a central focus of several theories of aging as a result of their critical role in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function coupled with the accumulation of oxidative damage to macromolecules may be causal to the decline in cardiac performance with age. In contrast, regular physical activity and lifelong caloric restriction can prevent oxidative stress, delay the onset of morbidity, increase life span, and reduce the risk of developing several pathological conditions. The health benefits of life long exercise and caloric restriction may be, at least partially, due to a reduction in the chronic amount of mitochondrial oxidant production. In addition, the available data suggest that chronic exercise may serve to enhance antioxidant enzyme activities, and augment certain repair/removal pathways, thereby reducing the amount of oxidative tissue damage. However, the characterization of age-related changes to cardiac mitochondria has been complicated by the fact that two distinct populations of mitochondria exist in the myocardium: subsar-colemmal mitochondria and interfibrillar mitochondria. Several studies now suggest the importance of studying both mitochondrial populations when attempting to elucidate the contribution of mitochondrial dysfunction to myocardial aging. The role that mitochondrial dysfunction and oxidative stress play in contributing to cardiac aging will be discussed along with the use of lifelong exercise and calorie restriction as countermeasures to aging. superoxide anion; longevity; postmitotic; calorie restriction; subsarcolemmal, interfibrillar, exercise doi:10.1152/ajpcell.00285.2006

Chronic constant hypoxia (CCH) and chronic intermittent hypoxia (CIH) are known to have deleterious effects on the central nervous system. Because of the difference in the pattern of hypoxic exposure, it is possible that the pathological outcome would vary. The N-acetyl aspartate/creatine (NAA/Cr) ratio is a reliable marker of neuronal integrity, and this can be noninvasively measured by proton nuclear magnetic resonance spectroscopy. P2 CD1 mouse pups with their dams were exposed to either CCH, where the [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII.] was maintained at 11% continuously or to CIH, where the [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII.], was varied between 21 and 11% every 4 min. P30 mice exposed to intermittent hypoxia for 4 wk demonstrated a significant decrease in the NAA/Cr ratio in the hippocampus and thalamus, which was reversed by a subsequent exposure to 4 wk of normoxia. Meanwhile, mice exposed to 4 wk of constant hypoxia did not demonstrate any differences in their NAA/Cr ratios from controls in these brain regions. These results indicate that an intermittent pattern of hypoxic exposure may have a more adverse effect on neuronal function and integrity than a continuous one. The reversal of NAA/Cr levels to baseline during the return to normoxia indicates that therapeutic strategies targeted at alleviating the intermittent hypoxic stress in diseases, such as obstructive sleep apnea, have the potential for inducing significant neurocognitive recovery in these patients. magnetic resonance imaging; energy metabolism; oxygen deprivation

The adult brain relies on glucose for its energy needs and stores it in the form of glycogen, primarily in astrocytes. Animal and culture studies indicate that brain glycogen may support neuronal function when the glucose supply from the blood is inadequate and/or during neuronal activation. However, the concentration of glycogen and rates of its metabolism in the human brain are unknown. We used in vivo localized [sup.13]C-NMR spectroscopy to measure glycogen content and turnover in the human brain. Nine healthy volunteers received intravenous infusions of [1-[sup.13]C]glucose for durations ranging from 6 to 50 h, and brain glycogen labeling and washout were measured in the occipital lobe for up to 84 h. The labeling kinetics suggest that turnover is the main mechanism of label incorporation into brain glycogen. Upon fitting a model of glycogen metabolism to the time courses of newly synthesized glycogen, human brain glycogen content was estimated at ~3.5 [micro]mol/g, i.e., three- to fourfold higher than free glucose at euglycemia. Turnover of bulk brain glycogen occurred at a rate of 0.16/[micro]mol*[g.sup.1-]*[h.sup.-1], implying that complete turnover requires 3-5 days. Twenty minutes of visual stimulation (n = 5) did not result in detectable glycogen utilization in the visual cortex, as judged from similar [[sup.13]C]glycogen levels before and after stimulation. We conclude that the brain stores a substantial amount of glycogen relative to free glucose and metabolizes this store very slowly under normal physiology. glucose; [sup.13]C nuclear magnetic resonance spectroscopy; visual stimulation

Brain cells are highly energy dependent for maintaining ion homeostasis during high metabolic activity. During active periods, full mitochondrial function is essential to generate ATP from electrons that originate with the oxidation of NADH. Decreasing brain metabolism is a significant cause of cognitive abnormalities of Alzheimer disease (AD), but it remains uncertain whether this is the cause of further pathology or whether synaptic loss results in a lower energy demand. Synapses are the first to show pathological symptoms in AD before the onset of clinical symptoms. Because synaptic function has high energy demands, interruption in mitochondrial energy supply could be the major factor in synaptic failure in AD. A newly discovered age-related decline in neuronal NADH and redox ratio may jeopardize this function. Mitochondrial dehydrogenases and several mutations affecting energy transfer are frequently altered in aging and AD. Thus, with the accumulation of genetic defects in mitochondria at the level of energy transfer, the issue of neuronal susceptibility to damage as a function of age and age-related disease becomes important. In an aging rat neuron model, mitochondria are both chronically depolarized and produce more reactive oxygen species with age. These concepts suggest that multiple treatment targets may be needed to reverse this multifactorial disease. This review summarizes new insights based on the interaction of mitoenergetic failure, glutamate excitotoxicity, and amyloid toxicity in the exacerbation of AD. bioenergetics; synaptic dysfunction; neurodegeneration; nicotinamide adenine dinucleotide; free radicals; mitochondrial membrane potential

Deficient bioenergetic signaling contributes to myocardial dysfunction and electrical instability in both atrial and ventricular cardiac chambers. Yet, approaches capable to prevent metabolic distress are only partially established. Here, in a canine model of tachycardia-induced congestive heart failure, we compared atrial and ventricular bioenergetics and tested the efficacy of metabolic rescue with the vasopeptidase inhibitor omapatrilat. Despite intrinsic differences in energy metabolism, failing atria and ventricles demonstrated profound bioenergetic deficiency with reduced ATP and creatine phosphate levels and compromised adenylate kinase and creatine kinase catalysis. Depressed phosphotransfer enzyme activities correlated with reduced tissue ATP levels, whereas creatine phosphate inversely related with atrial and ventricular load. Chronic treatment with omapatrilat maintained myocardial ATP, the high-energy currency, and protected adenylate and creatine kinase phosphotransfer capacity. Omapatrilat-induced bioenergetic protection was associated with maintained atrial and ventricular structural integrity, albeit without full recovery of the creatine phosphate pool. Thus therapy with omapatrilat demonstrates the benefit in protecting phosphotransfer enzyme activities and in preventing impairment of atrial and ventricular bioenergetics in heart failure. atria; ventricle; adenylate kinase; creatine kinase; energy metabolism; heart failure

Results indicate that the hydrophobic effect does not contribute much to the energetics of sequence-specific association of the DNA-binding domain of the murine PU.1 transcription factor to the gamma B site of the murine immunoglobulingamma 2-4 enhancer.

Research discusses the mechanism of nitric oxide reduction by nitric oxide reductase in bacteria. Data indicate a trans mechanism and involves the binuclear active site Fe(sub)B. Alternatively, nitric oxide reductase can also use a P-450-type mechanism with heme b(sub03 functioning as nitric oxide binding site.

Reaction centres are complexes of pigment and protein that convert the electromagnetic energy of sunlight into chemical potential energy. They are found in plants, algae and a variety of bacterial species, and vary greatly in their composition and complexity. New structural information has highlighted features that are common to the different types of reaction centre and has provided insights into some of the key differences between reaction centres from different sources. New ideas have also emerged on how contemporary reaction centres might have evolved and on the possible origin of the first chlorophyll-protein complexes to harness the power of sunlight.

Research has been conducted on the two sibling zooplankton copepod organisms. The differences in the life cycle timing among these species have been investigated with regard to foraging strategies, generation numbers, bioenergetics and predator avoidance.

Results show that Clostridium beijerinckii flavodoxin exhibits a sequence specificity of its reverse turn in association with flavin mononucleotide cofactor during modulation of its reduction potentials. Site-directed mutagenesis experiments demonstrate that there is a direct correlation between redox potentials and the conformational stability of the four-residue reverse turn.

Research was conducted to evaluate the action of carvacrol, a food additive, on food-borne pathogenic bacterial cells. Results show that the hydrophobic compound changes the permeability of cells, abolishing ion gradient, and causing cell death.

Intracellular PO2 of less than four mmHg is the critical level of O2 in the myocardium, below which a series of physiological and metabolic changes occur in the cells. At four mmHg of PO2, the formation of lactate increases while the rate pressure product decreases and at two mmHg there is a change in the myocardial O2 consumption and PCr. These changes are a result of the effect of low concentration of oxygen on NADP. If the intracellular PO2 is more than four mmHg the cell does not show any signs of oxygen starvation.

A study of the feeding habits of the two most abundant bioeroding parrotfish species on the Great Barrier Reef, Australia, Chlorurus gibbus and C. sordidus, reveals that both species have similar feeding patterns, which are initiated and terminated in an abrupt manner. While C. gibbus displayed limited time of day or seasonal variations in feeding rates, C. sordidus underwent major variations in feeding rates as a result of seasonal effects.

Estimates of metabolizability of organic matter, gross energy, nitrogen and cell wall parts of pelleted alfalfa by Lesser Snow Geese suggested correlations between body size of these birds and patterns of energy processing. These species and most other herbivorous birds, despite having good rates of energy-retention, seem to lose energy in the form of heat generated while eating.

A study of clutch size and removal indeterminacy of House Sparrows revealed the indeterminate pattern of laying eggs and the influence of endogenous energy reserves on the clutch size of these birds. Egg production in the species was directly influenced by the levels of exogenous and nutrient energy resources and only to a marginal degree by the female's endogenous reserves. The quantity of lipid reserves determine the clutch size in the females.

A study of the foraging strategies employed by 269 Wood Storks revealed their preference for straight flying paths in travelling to foraging sites in the vicinity of their colonies. Energy consumption in these birds remained stable, despite their usage of energetically conservative soaring flight in covering longer foraging distances at the end of their breeding season.

Filter-feeding marine macro-invertebrates process a large volume of water to satisfy their food requirements, and the process is associated with an energy cost. Each filter-feeder possesses a system and a pump, and a plot of pump and system characteristics in the same graph yields the operating point of the filter at the intersection of the two characteristics. The power output of various filter-pumps are evaluated from the product of volume flow rate and pump pressure and forms 0.3 to 4% of the total metabolic expenditure.

Analysis of whether the expression of one copy of obesity fatty (fa) gene influences energy balance in rats reveals that the fa gene copy number linearly influences inguinal adipose pads and body weight at 7 days of age and linearly influences inguinal adipose pads, body and interscapular brown adipose tissue weights at 14 days of age. The recessive effects and codominant effects of the fa gene are detectable in the first and second weeks of growth, respectively.

Labeling the apical endosomal route of the renal proximal tubule with ultrafiltrable fluorescent dextrans through intravenous infusion and measuring the energy transfer from the dextrans by fluorometry help assess endosomal fusion in rat renal cortical endosomes. The reduction in the fluorescein donor's fluorescence and the enhancement in the rhodamine acceptor's fluorescence represent the energy transfer, which has a narrow concentration dependence. Dual-beam two-color flow cytometric measurement of fluorescein-dextran and rhodamine-dextran in individual endosomes suggests the participation of many endosomes in each fusion event. Electron microscopic analysis reveals the fused heavy endosomal fractions to be five times wider than the endosomes without fusion.

Metabolic competence is discarded by the lecithotrophic larvae of Bugula neritina, a Cheilostome bryozoan, 12 to 24 hours after being released from the maternal zooid. The larvae exhibit active swimming behavior, which is revealed by their high rate of respiration. A 15. 24 milli Joule energy consumption is characteristic of all the larvae. Loss of metamorphic competence consumes 20% of the energy in the larvae.

Analysis of poststimulation energy metabolism in mice indicates that energy cost for maintenance of isometric tension is less in beta-guanidinopropionic acid (beta-GPA)-treated muscle cells than in control muscle cells. The first-order rate constant for O2 intake is higher in beta-GPA treated cells than in control cells. The high rate constants indicate that mitochondrial or cytoplasmic creatine kinase do not restrict cellular respiration.

Saccharomyces cerevisiae extends carboxyfluorescein (CF) in an energy dependent manner through a secondary transport system. Flow cytometry is used for rapid cell-by-cell analysis of efflux of CF from the cells, and the efflux is saturable and obeys Michaelis-Menten kinetics. Proton motive force is the driving force in the transport system of anionic compounds in S. cerevisiae.

The amino terminus of the TonB energy transducer protein contains an export signal and sequence-specific data that links the protein to the cytoplasmic membrane. Removal of TonB function does not affect TonB export when TetA membrane protein is substituted with TonB amino acid terminal. Amino acid terminal is not necessary for crosslinking of proteins with TonB structures. TonB is associated with cytoplasmic membrane even in the absence of amino acid terminus.

Study of human energy expenditure during exercise at 2500-3100 m elevations reveals that the doubly labeled water method is more accurate than the intake-balance method measuring the total daily energy expenditure. The execution of corrections for baseline isotopic abundance will yield similar estimates for both methods.

Experiments on partially lipectomized male Siberian hamsters reveal that these animals possess a photoperiod-dependent capacity to regulate total body fat. The recovery process contains fat pad-specific compensatory components. There is no overall increase in lipid deposition in fat depots. The crossing of the threshold between short-day and long-day status is essential for the compensatory response.

A study of preterm infants, incorporating the use of gradient-layer calorimeter, is used to calculate their energy expenditure. The total heat output can be separated into dry and wet constituents, respectively. The calorimeter used possesses an internal wall temperature higher than the room air temperature. Small preterm infants require calorimeters with a temperature of 10 degrees centigrade above normal room temperature.

An analysis of hindlimb muscle-tendon units in 35 quadrupedal species reveals that the springlike tendons of large animals may store larger amounts of elastic strain energy in comparison with the tendons of smaller mammals. This may be necessary because of stronger muscles that are capable of causing greater tendon stresses. Elastic energy storage in tendons is correlated with increasing positive allometry but exhibits isometric nature in digital extensors.

Studies on isolated rabbit heart reveal that enhanced Ca2+ affinity for contractile proteins is the major mechanism of length-dependent activation. The process does not have energy expenditure as a prerequisite. A multiple linear regression analysis reveals that left ventricle (LV) diastolic volume does not alter nonmechanical energy utilization over a range of LV end-diastolic pressure.

Fasted lean and fed and fasted obese rats are demonstrated in vivo to have mitochondrial metabolism dysfunction. Lowered phosphocreatine (PCr)/inorganic phosphate (Pi) and enhanced ADP are evidence for obese rats at rest. After stimulation-alternated PCr, regulating and ADP metabolization rate are evident.

Transformation of energy in aerobic organisms involves the consumption of oxygen by the terminal oxidase of oxidative phosphorylation systems. Energy transformation is essential for detoxification and biosynthetic processes. The transformation is retarded by the inhibitory effects of the oxygen molecule.

Constituents of an energy budget of an animal requires the allocation of metabolizable energy. The energy budget of an animal includes its growth, maintenance, activity and reproduction mechanisms. The allocation is performed by the application of Winberg's 'balanced energy equation.'

A bacterial strain, Acinetobacter junii 5ga, which uses guaiacol as the only carbon and energy source, helps in the metabolism of chlorinated guaiacols. 4- and 5-chloroguaiacol and 4,5-dichloroguaiacol are broken by the 5ga strain developed on guaiacol which does not develop on many chlorinated guaiacols and catechols. The 5ga strain induces metabolism of particular chlorinated guaiacols by O-demethylation.

The inner membrane potential (delta Xi) of individual mitochondria equals 117 millivolts, as derived by the Nernst equation. Hexakis (2-methoxyisobutylisonitrile) technetium-99m (Tc99m-MIBI) is localized in the mitochondria as a function of the membrane potential in a Nernstian manner, and provides valuable insight into cellular bioenergetics by evaluating delta xi. Electron-probe X-ray microanalysis (EPXMA) of the distribution of the gamma-emitting radio pharmaceutical probe in the heart tissue is conducted. Prior to this analysis, the micromolar concentrations of the carrier-added TC99-MIBI is brought to equilibrium.

The interaction between the ruminal microflora and the host is examined by correlating bacterial diversity with fermentation measurements and feed efficiency traits, including dry matter intake, feed conversion ratio, average daily gain and residual feed intake, by using culture-independent methods. The results have shown that particular bacteria and their metabolism in the rumen has contributed to differences in host feed efficiency under a low-energy diet and have also correlated PCR-denaturing gradient gel electrophoresis (DGGE) bands representing specific bacteria to metabolites in the bovine rumen and to host feed efficiency traits.

Suppression hybridization is used for identifying the genes present in Fibrobacter succinogenes S85 but absent from Fibrobacter intestinalis DR7. Two gene clusters encoding NADH-ubiquinone oxidoreductase subunits shared by Fibrobacter genera have played a vital role in energy metabolism.

Oxygen is vital for the conversion of food into energy and for basic metabolic processes such as tissue respiration. The daily oxygen consumption of an average individual is equal to the amount of daily food intake. Quantitative analysis of oxygen consumption indicated that a moderately active individual needs 1.5 pounds of oxygen to metabolize 1.4 pounds of food which generate 3,000 kilocalories of energy.

Halophilic microorganisms spend large amounts of energy to maintain steep gradients of K+ and NA+ concentrations across their cytoplasmic membrane. The energetic cost of salt adaptation can probably determine what kind of metabolism can support life at the highest salt concentration. The halophilic homoacetogenic bacteria uses KCl as an intracellular solute to exist while producing acetate from H2 + CO2.