Energy Status (energy + status)

Distribution by Scientific Domains

Kinds of Energy Status

  • cellular energy status

  • Selected Abstracts

    Regulation of glucose transporter 4 traffic by energy deprivation from mitochondrial compromise

    ACTA PHYSIOLOGICA, Issue 1 2009
    A. Klip
    Abstract Skeletal muscle is the major store and consumer of fatty acids and glucose. Glucose enters muscle through glucose transporter 4 (GLUT4). Upon insufficient oxygen availability or energy compromise, aerobic metabolism of glucose and fatty aids cannot proceed, and muscle cells rely on anaerobic metabolism of glucose to restore cellular energy status. An increase in glucose uptake into muscle is a key response to stimuli requiring rapid energy supply. This chapter analyses the mechanisms of the adaptive regulation of glucose transport that rescue muscle cells from mitochondrial uncoupling. Under these conditions, the initial drop in ATP recovers rapidly, through a compensatory increase in glucose uptake. This adaptive response involves AMPK activation by the initial ATP drop, which elevates cell surface GLUT4 and glucose uptake. The gain in surface GLUT4 involves different signals and routes of intracellular traffic compared with those engaged by insulin. The hormone increases GLUT4 exocytosis through phosphatidylinositol 3-kinase and Akt, whereas energy stress retards GLUT4 endocytosis through AMPK and calcium inputs. Given that energy stress is a component of muscle contraction, and that contraction activates AMPK and raises cytosolic calcium, we hypothesize that the increase in glucose uptake during contraction may also involve a reduction in GLUT4 endocytosis. [source]

    LKB1 and AMP-activated protein kinase control of mTOR signalling and growth

    ACTA PHYSIOLOGICA, Issue 1 2009
    R. J. Shaw
    Abstract The AMP-activated serine/threonine protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes that is activated under conditions of low intracellular ATP following stresses such as nutrient deprivation or hypoxia. In the past 5 years, work from a large number of laboratories has revealed that one of the major downstream signalling pathways regulated by AMPK is the mammalian target-of-rapamycin [mammalian target of rapamycin (mTOR) pathway]. Interestingly, like AMPK, the mTOR serine/threonine kinase plays key roles not only in growth control and cell proliferation but also in metabolism. Recent work has revealed that across eukaryotes mTOR orthologues are found in two biochemically distinct complexes and only one of those complexes (mTORC1 in mammals) is acutely sensitive to rapamycin and regulated by nutrients and AMPK. Many details of the molecular mechanism by which AMPK inhibits mTORC1 signalling have also been decoded in the past 5 years. AMPK directly phosphorylates at least two proteins to induce rapid suppression of mTORC1 activity, the TSC2 tumour suppressor and the critical mTORC1 binding subunit raptor. Here we explore the molecular connections between AMPK and mTOR signalling pathways and examine the physiological processes in which AMPK regulation of mTOR is critical for growth or metabolic control. The functional conservation of AMPK and TOR in all eukaryotes, and the sequence conservation around the AMPK phosphorylation sites in raptor across all eukaryotes examined suggest that this represents a fundamental cell growth module connecting nutrient status to the cell growth machinery. These findings have broad implications for the control of cell growth by nutrients in a number of cellular and organismal contexts. [source]

    Neurophysiology of hunger and satiety

    Pauline M. Smith
    Abstract Hunger is defined as a strong desire or need for food while satiety is the condition of being full or gratified. The maintenance of energy homeostasis requires a balance between energy intake and energy expenditure. The regulation of food intake is a complex behavior. It requires discrete nuclei within the central nervous system (CNS) to detect signals from the periphery regarding metabolic status, process and integrate this information in a coordinated manner and to provide appropriate responses to ensure that the individual does not enter a state of positive or negative energy balance. This review of hunger and satiety will examine the CNS circuitries involved in the control of energy homeostasis as well as signals from the periphery, both hormonal and neural, that convey pertinent information regarding short-term and long-term energy status of the individual. 2008 Wiley-Liss, Inc. Dev Disabil Res Rev 2008;14:96,104. [source]

    Integrated regulation in response to aromatic compounds: from signal sensing to attractive behaviour

    Victoria Shingler
    Summary Deciphering the complex interconnecting bacterial responses to the presence of aromatic compounds is required to gain an integrated understanding of how aromatic catabolic processes function in relation to their genome and environmental context. In addition to the properties of the catabolic enzymes themselves, regulatory responses on at least three different levels are important. At a primary level, aromatic compounds control the activity of specific members of many families of transcriptional regulators to direct the expression of the specialized enzymes for their own catabolism. At a second level, dominant global regulation in response to environmental and physiological cues is incorporated to subvert and couple transcription levels to the energy status of the bacteria. Mediators of these global regulatory responses include the alarmone (p)ppGpp, the DNA-bending protein IHF and less well-defined systems that probably sense the energy status through the activity of the electron transport chain. At a third level, aromatic compounds can also impact on catabolic performance by provoking behavioural responses that allow the bacteria to seek out aromatic growth substrates in their environment. [source]

    The role of metabolic memory in the ATP paradox and energy homeostasis

    FEBS JOURNAL, Issue 21 2008
    Juan C. Aledo
    In yeast, a sudden transition from glucose limitation to glucose excess leads to a new steady state at increased metabolic fluxes with a sustained decrease in the ATP concentration. Although this behaviour has been rationalized as an adaptive metabolic strategy, the mechanism behind it remains unclear. Nevertheless, it is thought that, on glucose addition, a metabolite derived from glycolysis may up-regulate ATP-consuming reactions. The adenine nucleotides themselves have been ruled out as the signals that mediate this regulation. This is mainly because, in that case, it would be expected that the new steady state at increased fluxes would be accompanied by an increased stationary ATP concentration. In this study, we present a core model consisting of a monocyclic interconvertible enzyme system. Using a supply,demand approach, we demonstrate that this system can account for the empirical observations without involving metabolites other than the adenine nucleotides as effectors. Moreover, memory is an emerging property of such a system, which may allow the cell to sense both the current energy status and the direction of the changes. [source]

    ATP-dependent modulation and autophosphorylation of rapeseed 2-Cys peroxiredoxin

    FEBS JOURNAL, Issue 7 2008
    Martin Aran
    2-Cys peroxiredoxins (2-Cys Prx) are ubiquitous thiol-containing peroxidases that have been implicated in antioxidant defense and signal transduction. Although their biochemical features have been extensively studied, little is known about the mechanisms that link the redox activity and non-redox processes. Here we report that the concerted action of a nucleoside triphosphate and Mg2+ on rapeseed 2-Cys Prx reversibly impairs the peroxidase activity and promotes the formation of high molecular mass species. Using protein intrinsic fluorescence in the analysis of site-directed mutants, we demonstrate that ATP quenches the emission intensity of Trp179, a residue close to the conserved Cys175. More importantly, we found that ATP facilitates the autophosphorylation of 2-Cys Prx when the protein is successively reduced with thiol-bearing compounds and oxidized with hydroperoxides or quinones. MS analyses reveal that 2-Cys Prx incorporates the phosphoryl group into the Cys175 residue yielding the sulfinic-phosphoryl [Prx-(Cys175)-SO2PO32,] and the sulfonic-phosphoryl [Prx-(Cys175)-SO3PO32,] anhydrides. Hence, the functional coupling between ATP and 2-Cys Prx gives novel insights into not only the removal of reactive oxygen species, but also mechanisms that link the energy status of the cell and the oxidation of cysteine residues. [source]

    High expression of a sucrose non-fermenting (SNF1)-related protein kinase from Colletotrichum gloeosporoides f. sp. malvae is associated with penetration of Malva pusilla,

    Paul H Goodwin
    Abstract A sucrose non-fermenting (SNF1)-related protein kinase homologue, cgsnf, from Colletotrichum gloeosporoides f. sp. malvae, a hemibiotrophic fungal pathogen of round-leaved mallow (Malva pusilla) was examined. During infection, cgsnf showed a large peak in expression relative to a constitutively expressed fungal actin gene when appressoria had formed during the penetration phase and then showed much lower expression levels during subsequent necrotrophic growth in the host. In pure culture with glucose or glycerol as sole carbon sources, expression levels were similar to that during necrotrophic growth. Expression was consistently higher in glycerol than in glucose cultures, which may reflect a lower cellular energy status in the fungus. These results are consistent with cgsnf having a role in transmitting nutritional signals, which may be involved with host penetration. [source]

    Swimming activity and behaviour of European Anguilla anguilla glass eels in response to photoperiod and flow reversal and the role of energy status

    S. Bureau Du Colombier
    To better understand migratory divergences among Anguilla anguilla glass eels, the behaviour of individuals caught at the time of their estuary entrance was studied through their response to a light:dark cycle and then to both water current reversal and light:dark cycle. In a first experiment, fish moving with the flow in response to dusk (M+ fish) and fish that had not exhibited any movement (M, fish) were distinguished. Anguilla anguilla from these two groups were then individually marked and their response to water current reversal compared. M+ individuals mainly exhibited negative rheotaxis with a tidal periodicity, whereas positive rheotaxis was mainly exhibited by M, individuals. Thus, M+A. anguilla glass eels showing negative rheotaxis appear to have the strongest propensity to migrate, the converse applies to M, ones showing positive rheotaxis. A small percentage of individuals (5%) were hyperactive, alternately swimming with and against the current with almost no resting phase. These fish lost c. 2 mg wet mass day,1, whereas individuals which were almost inactive lost c. 1 mg day,1. Wet and dry mass changes in relation to activity levels were compared with previous experiments and it was concluded that A. anguilla glass eel energy status might be involved in differences in migratory tendencies but other factors that might be important are discussed. It is proposed that any decrease in A. anguilla glass eel energy stores associated with global warming might lead to an increase in the proportion of sedentary individuals and thus be involved in the decrease in the recruitment to freshwater habitats. [source]

    Temperature-dependent changes in energy metabolism, intracellular pH and blood oxygen tension in the Atlantic cod

    F. J. Sartoris
    The effect of acute increase in temperature on oxygen partial pressure (Po2) was measured in the gill arches of Atlantic cod Gadus morhua between 10 and 19 C by use of oxygen microoptodes. Oxygen saturation of the gill blood under control conditions varied between 90 and 15% reflecting a variable percentage of arterial or venous blood in accordance with the position of each optode in the gill arch. The data obtained suggested that arterial Po2 remained more or less constant and arterial oxygen uptake did not become limiting during warming. A progressive drop in venous Po2, however, was observed at >10 C indicating that excessive oxygen uptake from the blood is not fully compensated for by circulatory performance, until finally, Po2 levels fully collapse. In a second set of experiments energy and acid,base status of white muscle of Atlantic cod in vivo was measured by magnetic resonance (31P-NMR) spectroscopy in unanaesthetized and unimmobilized fish in the temperature range between 13 and 21 C. A decrease in white muscle intracellular pH (pHi) with temperature occurred between 10 and 16 C (,pH per C = ,0025 per C). In white muscle temperature changes had no influence on high-energy phosphates such as phosphocreatine (PCr) or ATP except during exposure to high critical temperatures (>16 C), indicating that white muscle energy status appears to be relatively insensitive to thermal stress if compared to the thermal sensitivity of the whole animal. The data were consistent with the hypothesis of an oxygen limitation of thermal tolerance in animals, which is set by limited capacity of oxygen supply mechanisms. In the case of Atlantic cod circulatory rather than ventilatory performance may be the first process to cause oxygen deficiency during heat stress. [source]

    Salt stress and resistance to hypoxic challenges in the common carp (Cyprinus carpio L.)

    G. De Boeck
    Long term exposure to brackish water (171 mm NaCl) affected the capacity of common carp Cyprinus carpio to deal with hypoxic conditions and the critical oxygen concentrations for oxygen consumption increased. In addition, regulation of ammonia excretion was lost. The cytosolic phosphorylation potential (the index of the energy status of a cell in terms of potential transferable phosphate groups) in the lateral muscle on the other hand remained relatively unaffected, indicating that oxygen transport to the tissues was not severely compromised. It appears that exposure to brackish water reduces the capacity of common carp to cope with hypoxic conditions mainly because of the high energetic cost of hyperventilation under conditions where energy stores are depleted, and not because of any impeded oxygen transport mechanisms. [source]

    Muscle mitochondrial activity increases rapidly after an endotoxin challenge in human volunteers

    Background: Mitochondrial derangements in muscle of patients suffering from sepsis have been established in several studies and have been related to muscle dysfunction and organ failure. It is not possible to study the early phase of sepsis in patients; therefore, we used a human endotoxaemia model to study the effect of early sepsis on muscle mitochondria. Methods: Seven healthy male volunteers received a standardised endotoxin challenge. Muscle biopsies were obtained immediately before the challenge, and at 2 and 4 h following the endotoxin challenge. The muscle biopsies were analysed for maximal activities of citrate synthase and complexes I and IV of the respiratory chain. In addition, total and mitochondrial superoxide dismutase (SOD) activities were analysed. The concentrations of ATP, creatine phosphate and lactate were analysed to assess the cellular energy status. Total and phosphorylated AMP-activated protein kinase (AMPK-P), a key regulator in intracellular energy metabolism, was measured. Results: Activities of citrate synthase and complex I were significantly increased 2 h after the endotoxin challenge. SOD activities were unaffected by the endotoxin challenge. No changes in ATP, creatine phosphate or lactate were observed. Neither total nor AMPK-P changed. Conclusions: An endotoxin challenge given to healthy volunteers rapidly increases mitochondrial enzyme activity in skeletal muscle. The results of this human model indicate that possibly early during sepsis, mitochondrial activity might be increased in contrast to what has been shown in the later phases of sepsis. It is possible that this early activation leads to exhaustion of the mitochondria and a decreased function later during sepsis. [source]

    Altered distribution of mitochondria impairs calcium homeostasis in rat hippocampal neurons in culture

    Guang Jian Wang
    Abstract The specificity of Ca2+ signals is conferred in part by limiting changes in cytosolic Ca2+ to subcellular domains. Mitochondria play a major role in regulating Ca2+ in neurons and may participate in its spatial localization. We examined the effects of changes in the distribution of mitochondria on NMDA-induced Ca2+ increases. Hippocampal cultures were treated with the microtubule-destabilizing agent vinblastine, which caused the mitochondria to aggregate and migrate towards one side of the neuron. This treatment did not appear to decrease the energy status of mitochondria, as indicated by a normal membrane potential and pH gradient across the inner membrane. Moreover, electron microscopy showed that vinblastine treatment altered the distribution but not the ultrastructure of mitochondria. NMDA (200 m, 1 min) evoked a greater increase in cytosolic Ca2+ in vinblastine-treated cells than in untreated cells. This increase did not result from impaired Ca2+ efflux, enhanced Ca2+ influx, opening of the mitochondrial permeability transition pore or altered function of endoplasmic reticulum Ca2+ stores. Ca2+ uptake into mitochondria was reduced by 53% in vinblastine-treated cells, as reported by mitochondrially targeted aequorin. Thus, the distribution of mitochondria maintained by microtubules is critical for buffering Ca2+ influx. A subset of mitochondria close to a Ca2+ source may preferentially regulate Ca2+ microdomains, set the threshold for Ca2+ -induced toxicity and participate in local ATP production. [source]

    Protection from MPTP-induced neurotoxicity in differentiating mouse N2a neuroblastoma cells

    Luigi A. De Girolamo
    We have shown previously that subcytotoxic concentrations of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) inhibit axon outgrowth and are associated with increased neurofilament heavy chain (NF-H) phosphorylation in differentiating mouse N2a neuroblastoma cells while higher doses (>,100 m) cause cell death. In this work we assessed the ability of potential neuroprotective agents to alleviate both MPTP-induced cell death (cytotoxicity) and MPTP-induced NF-H phosphorylation/reduction in axon outgrowth (neurotoxicity) in N2a cells induced to differentiate by dbcAMP. The neurotoxic effects of MPTP occurred in the absence of significant alterations in energy status or mitochondrial membrane potential. The hormone oestradiol (100 m) reduced the cytotoxic effect of MPTP, but blocked di-butyryl cyclic AMP (dbcAMP)-induced differentiation, i.e. axon outgrowth. Both the cytotoxic and neurotoxic effects of MPTP were reduced by the monoamine osidase (MAO) inhibitors deprenyl and, to a lesser extent, clorgyline. Alleviation of both neurotoxicity and cytotoxicity was also achieved by conditioned medium derived from rat C6 glioma cells. In contrast, whilst the p38 MAP kinase inhibitor, SB202190, protected cells against MPTP-induced neurotoxicity, it could not maintain cell viability at high MPTP exposures. In each case neuroprotection involved maintenance of the differentiating phenotype linked with attenuation of NF-H hyper-phosphorylation; the latter may represent a mechanism by which neuronal cells can moderate MPTP-induced neurotoxicity. The use of a simplified neuronal cell model, which expresses subtle biochemical changes following neurotoxic insult, could therefore provide a valuable tool for the identification of potential neuroprotective agents. [source]

    Short-term administration of (-)-epigallocatechin gallate reduces hepatic steatosis and protects against warm hepatic ischemia/reperfusion injury in steatotic mice

    Ryan N. Fiorini
    Hepatic steatosis increases the extent of cellular injury incurred during ischemia/reperfusion (I/R) injury. (-)-Epigallocatechin gallate (EGCG), the major flavonoid component of green tea (camellia sinensis) is a potent antioxidant that inhibits fatty acid synthase (FAS) in vitro. We investigated the effects of EGCG on hepatic steatosis and markers of cellular damage at baseline and after I/R injury in ob/ob mice. Animals were pretreated with 85 mg/kg EGCG via intraperitoneal (ip) injection for 2 days or oral consumption in the drinking water for 5 days before 15 minutes of warm ischemia and 24 hours of reperfusion. After EGCG administration, total baseline hepatic fat content decreased from baseline. Palmitic acid and linoleic acid levels also were reduced substantially in all ECGC-treated animals before I/R. Alanine aminotransferase (ALT) levels decreased in all EGCG-treated animals compared with control animals after I/R. Histologic analysis demonstrated an average decrease of 65% necrosis after EGCG administration. EGCG administration also increased resting hepatic energy stores as determined by an increase in cellular adenosine triphosphate (ATP) with a concomitant decrease in uncoupling protein 2 (UCP2) before I/R. Finally, there was an increased level of glutathione (GSH) in the EGCG-treated mice compared with the vehicle-treated mice both at baseline and after I/R. In conclusion, taken together, this study demonstrates that treatment with ECGC by either oral or ip administration, significantly protects the liver after I/R, possibly by reducing hepatic fat content, increasing hepatic energy status, and functioning as an antioxidant. (Liver Transpl 2005;11:298,308.) [source]

    Proteomics analysis of hypothalamic response to energy restriction in dairy cows

    Bjrn Kuhla
    Abstract The hypothalamus is the central regulatory unit that balances a number of body functions including metabolic rate, hunger, and satiety signals. Hypothalamic neurons monitor and respond to alterations of circulating nutrients and hormones that reflect the peripheral energy status. These extracellular signals are integrated within the cell at the ATP:AMP ratio and at the level of ROS, triggering gene expression associated with glucose and lipid metabolism. In order to identify new molecular factors potentially associated with the control of energy homeostasis, metabolic adaptation, and regulation of feed intake, hypothalami from ad libitum fed and energy restricted cows were characterized using 2-DE and MALDI-TOF-MS. Among 189 different protein spots identified, nine proteins were found to be differentially expressed between groups. Beside the 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase, stress-induced phosphoprotein-1, heat shock protein 70,kDa-protein-5, dihydropyrimidinase-related protein-2, [Cu-Zn]-superoxide dismutase, ubiquitin carboxy-terminal hydrolase-L1, and inorganic pyrophosphatase were found to be up-regulated, whereas glyceraldehyde 3-phosphate dehydrogenase and aconitase-2 were down-regulated in the restricted group. In conclusion, differentially expressed proteins are related to energy and nucleotide metabolism and cellular stress under conditions of dietary energy deficiency. These proteins may be new candidate molecules that are potentially involved in signaling for maintaining energy homeostasis. [source]

    Testosterone, physical activity, and somatic outcomes among Filipino males

    Lee T. Gettler
    Abstract Testosterone (T) facilitates male investment in reproduction in part through its anabolic effects on skeletal muscle. Traits like muscle and strength are energetically costly but are believed to enhance competitive ability in humans and other mammals. However, there are limited data on relationships between T and somatic outcomes in lean, non-western populations. We evaluate relationships between waking and pre-bed salivary T and adiposity, fat-free mass (FFM), arm muscle area (AMA), and grip strength (GS) in a large, population-based birth cohort of young adult Filipino males (20.8,22.6 years, n = 872). Data were collected as part of the Cebu Longitudinal Health and Nutrition Survey. Neither waking nor evening T predicted FFM, AMA, or GS. However, there were borderline or significant interactions between T and basketball playing (the most common team sport) and weight lifting as predictors of outcomes: higher waking T predicted higher FFM (activity T interaction P < 0.01), AMA (interaction P < 0.1), and GS (interaction P < 0.02) among frequent basketball players, and GS (interaction P < 0.09) among the smaller sample of weight lifters. In contrast to clinical studies, but consistent with findings in several subsistence-level populations, T was positively related to adiposity in these lean young males, suggesting that energy status might regulate circulating T. Our findings support a role of the prewaking rise in T as a determinant of energetic allocation to lean mass and strength in the context of repeated muscular use and support the hypothesized role of T as a mediator of investment in costly somatic traits in human males. Am J Phys Anthropol 142:590,599, 2010. 2010 Wiley-Liss, Inc. [source]

    Cryotolerance of Bovine Blastocysts is Affected by Oocyte Maturation in Media Containing Palmitic or Stearic Acid

    MA Shehab-El-Deen
    Contents In this study, non-esterified fatty acids (NEFAs) were added during in vitro maturation at concentrations measured previously in follicular fluid (FF) of high-producing dairy cows in a negative energy status to evaluate their subsequent effect on the embryos cryotolerance. Oocytes were matured for 24 h in serum-free media with or without (negative control) the addition of NEFAs dissolved in ethanol or ethanol alone (positive control). Matured oocytes were fertilized and cultured for 7 days in synthetic oviduct fluid medium supplemented with 5% FCS. Embryos that had at least reached the blastocyst stage were vitrified by open pulled straw (OPS) vitrification. Addition of palmitic (C16 : 0) or stearic acid (C18 : 0) during oocyte maturation had significant negative effects on embryo cryotolerance, whereas ethanol or oleic acid (C18 : 1) had no effect. These in vitro results suggest that high NEFA concentrations in FF during a period of negative energy balance in high-yielding dairy cows can have carry-over effects on embryo quality. [source]

    AMP-activated protein kinase signalling pathways are down regulated and skeletal muscle development impaired in fetuses of obese, over-nourished sheep

    Mei J. Zhu
    Maternal obesity and over-nutrition give rise to both obstetric problems and neonatal morbidity. The objective of this study was to evaluate effects of maternal obesity and over-nutrition on signalling of the AMP-activated protein kinase (AMPK) pathway in fetal skeletal muscle in an obese pregnant sheep model. Non-pregnant ewes were assigned to a control group (Con, fed 100% of NRC nutrient recommendations, n= 7) or obesogenic group (OB, fed 150% of National Research Council (NRC) recommendations, n= 7) diet from 60 days before to 75 days after conception (term 150 days) when fetal semitendinosus skeletal muscle (St) was sampled. OB mothers developed severe obesity accompanied by higher maternal and fetal plasma glucose and insulin levels. In fetal St, activity of phosphoinositide-3 kinase (PI3K) associated with insulin receptor substrate-1 (IRS-1) was attenuated (P < 0.05), in agreement with the increased phophorylation of IRS-1 at serine 1011. Phosphorylation of AMP-activated protein kinase (AMPK) at Thr 172, acetyl-CoA carboxylase at Ser 79, tuberous sclerosis 2 at Thr 1462 and eukaryotic translation initiation factor 4E-binding protein 1 at Thr 37/46 were reduced in OB compared to Con fetal St. No difference in energy status (AMP/ATP ratio) was observed. The expression of protein phosphatase 2C was increased in OB compared to Con fetal St. Plasma tumour necrosis factor , (TNF,) was increased in OB fetuses indicating an increased inflammatory state. Expression of peroxisome proliferator-activated receptor , (PPAR,) was higher in OB St, indicating enhanced adipogenesis. The glutathione: glutathione disulphide ratio was also lower, showing increased oxidative stress in OB fetal St. In summary, we have demonstrated decreased signalling of the AMPK system in skeletal muscle of fetuses of OB mothers, which may play a role in altered muscle development and development of insulin resistance in the offspring. [source]

    Metabolic systems maintain stable non-equilibrium via thermodynamic buffering

    BIOESSAYS, Issue 10 2009
    Abir U. Igamberdiev
    Abstract Here, we analyze how the set of nucleotides in the cell is equilibrated and how this generates simple rules that help the cell to organize itself via maintenance of a stable non-equilibrium state. A major mechanism operating to achieve this state is thermodynamic buffering via high activities of equilibrating enzymes such as adenylate kinase. Under stable non-equilibrium, the ratios of free and Mg-bound adenylates, Mg2+ and membrane potentials are interdependent and can be computed. The adenylate status is balanced with the levels of reduced and oxidized pyridine nucleotides through regulated uncoupling of the pyridine nucleotide pool from ATP production in mitochondria, and through oxidation of substrates non-coupled to NAD+ reduction in peroxisomes. The set of adenylates and pyridine nucleotides constitutes a generalized cell energy status and determines rates of major metabolic fluxes. As the result, fluxes of energy and information become organized spatially and temporally, providing conditions for self-maintenance of metabolism. [source]

    More TORC for the gluconeogenic engine

    BIOESSAYS, Issue 3 2006
    Alan Cheng
    Hepatic gluconeogenesis plays a key role in the maintenance of glucose homeostasis. The hormone glucagon stimulates this process, whereas insulin and adiponectin are inhibitory. In a recent report, Koo et al identify the transcriptional regulator TORC2 (Transducer of Regulated CREB activity 2) as a pivotal component of the gluconeogenic program.1 Both insulin and AMPK increase the phosphorylation of TORC2, while glucagon suppresses it. This in turn regulates the nuclear/cytoplasmic shuttling of TORC2 and its ability to transactivate gluconeogenic genes. Thus, TORC2 might serve as a gluconeogenic "molecular switch" that senses hormones and cellular energy status. BioEssays 28: 231,234, 2006. 2006 Wiley Periodicals, Inc. [source]

    Purification, crystallization and preliminary crystallographic analysis of protein MJ1225 from Methanocaldococcus jannaschii, a putative archaeal homologue of ,-AMPK

    Inmaculada Gmez Garca
    In mammals, AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic serine/threonine kinase subunit (,) and two regulatory subunits (, and ,). The , subunit senses the intracellular energy status by competitively binding AMP and ATP and is thought to be responsible for allosteric regulation of the whole complex. This work describes the purification and preliminary crystallographic analysis of protein MJ1225 from Methanocaldococcus jannaschii, an archaeal homologue of ,-AMPK. The purified protein was crystallized using the hanging-drop vapour-diffusion method. Diffraction data for MJ1225 were collected to 2.3, resolution using synchrotron radiation. The crystals belonged to space group H32, with unit-cell parameters a = b = 108.95, c = 148.08,, , = , = 90.00, , = 120.00. Preliminary analysis of the X-ray data indicated that there was one molecule per asymmetric unit. [source]

    KC 12291: An Atypical Sodium Channel Blocker with Myocardial Antiischemic Properties

    Gareth W. John
    ABSTRACT KC 12291 was designed as a voltage-gated sodium channel (VGSC) blocker with cardioprotective properties. KC 12291 has moderate inhibitory effects on peak (or rapid) Na+ current, and markedly reduces sustained (or slowly or non-inactivating) Na+ current. This distinguishes KC 12291 from conventional VGSC blockers such as local anesthetics or antiarrhythmics, which have little or no cardioprotective properties. Since VGSCs represent the main pathway for ischemic Na+ loading by failing to inactivate fully, KC 12291 exerts pronounced antiischemic activity principally by reducing the amplitude of sustained Na+ current. In isolated atria and Langendorff-perfused hearts, KC 12291 inhibits diastolic contracture, renowned for its resistance to pharmacological inhibition, reduces ischemic Na+ loading and preserves cardiac energy status. KC 12291 exerts oral antiischemic activity in vivo in the absence of major hemodynamic effects. Cardiac VGSC blockers such as KC 12291, which block cardiac VGSCs in atypical fashion by effectively inhibiting the sustained component of Na+ current, represent, therefore, promising potential antiischemic and cardioprotective drugs. [source]