Home About us Contact
|
Home About us Contact | ||
|
|
||
Metabolic Systems (metabolic + system)
Selected AbstractsMetabolic systems maintain stable non-equilibrium via thermodynamic bufferingBIOESSAYS, Issue 10 2009Abir 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] Brain regulation of food intake and appetite: molecules and networksJOURNAL OF INTERNAL MEDICINE, Issue 4 2005C. BROBERGER Abstract. In the clinic, obesity and anorexia constitute prevalent problems whose manifestations are encountered in virtually every field of medicine. However, as the command centre for regulating food intake and energy metabolism is located in the brain, the basic neuroscientist sees in the same disorders malfunctions of a model network for how integration of diverse sensory inputs leads to a coordinated behavioural, endocrine and autonomic response. The two approaches are not mutually exclusive; rather, much can be gained by combining both perspectives to understand the pathophysiology of over- and underweight. The present review summarizes recent advances in this field including the characterization of peripheral metabolic signals to the brain such as leptin, insulin, peptide YY, ghrelin and lipid mediators as well as the vagus nerve; signalling of the metabolic sensors in the brainstem and hypothalamus via, e.g. neuropeptide Y and melanocortin peptides; integration and coordination of brain-mediated responses to nutritional challenges; the organization of food intake in simple model organisms; the mechanisms underlying food reward and processing of the sensory and metabolic properties of food in the cerebral cortex; and the development of the central metabolic system, as well as its pathological regulation in cancer and infections. Finally, recent findings on the genetics of human obesity are summarized, as well as the potential for novel treatments of body weight disorders. [source] Abnormal alterations in the metabolic patterns of patients on valproate therapyJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2002U. Kreher Four cases of abnormal metabolic patterns which were obtained from three infantile patients and one adult on valproate (valproic acid; 2-n-propyl-pentanoic acid) therapy are reported. Serum levels of valproate and 15 metabolites were measured by gas chromatography/mass spectrometry. A mentally retarded, 11-month-old boy developed an extremely altered metabolic profile after having been treated with valproate polytherapy for 3 months. The altered pattern included strongly elevated serum levels of the 4-ene as well as of the x-/x 1-metabolites, with the b-metabolites (2-ene; 2,3,-diene) being diminished. Two samples obtained previously had shown a common pattern. The infant died 3 weeks after the last sample had been taken. Two boys of the same age showed similar but less intense deviations in their metabolic profiles at the onset of valproate therapy. Within a few weeks they approached, in a step-wise fashion, the average pattern common for children under 3 years of age. The striking alterations were paralleled by the metabolic profiles of an adult patient who suffered from intrahepatic metastasis and renal insufficiency. From the close resemblance of the abnormal metabolic patterns it was concluded that liver dysfunction results in alteration of the whole metabolic system. Regular inspection of the entire profile of an individual might help to recognize conspicuous alterations in time to avoid severe side effects. [source] Cytochromes P450 of insects: the tip of the iceberg,PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 10 2001Jeffrey G Scott Abstract The cytochrome P450-dependent monooxygenases are an extremely important metabolic system involved in the metabolism of endogenous compounds and xenobiotics. Collectively, P450 monooxygenases can metabolize numerous substrates and carry out multiple oxidative reactions. The large number of substrates metabolized is due to the plethora of P450 isoforms and to the broad substrate specificity of some isoforms. Monooxygenases of insects have several functional roles, including growth, development, feeding and protection against xenobiotics, including resistance to pesticides and tolerance to plant toxins. This review begins with background information about P450s and their evolution, followed by a discussion of the extraordinary diversity of insect P450s. Given the enormous interest in studying individual P450s, we then provide a synopsis of the different methods that have been used in their isolation and the substrates that are known to be metabolized. We conclude by summarizing the lessons we have learned from the study of individual insect P450s, including their roles in insecticide resistance, plant,insect interactions and insect physiology. However, these studies are just the ,tip of the iceberg'. Our knowledge continues to expand at a rapid pace, suggesting that the next decade will outpace the last in terms of improving our understanding of the cytochromes P450 of insects. © 2001 Society of Chemical Industry [source] Pharmacodynamics of glucose regulation by methylprednisolone.BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2009II. normal rats Abstract A physiologic pharmacodynamic model was developed to jointly describe the effects of methylprednisolone (MPL) on adrenal suppression and glycemic control in normal rats. Six groups of animals were given MPL intravenously at 0, 10 and 50,mg/kg, or by subcutaneous 7 day infusion at rates of 0, 0.1 and 0.3,mg/kg/h. Plasma concentrations of MPL, corticosterone (CST), glucose and insulin were determined at various times up to 72,h after injection and 336,h after infusion. The pharmacokinetics of MPL was described by a two-compartment model. A circadian rhythm for CST was found in untreated rats with a stress-altered baseline caused by handling, which was captured by a circadian harmonic secretion rate with an increasing mesor. All drug treatments caused CST suppression. Injection of MPL caused temporary increases in glucose over 4,h. Insulin secretion was thereby stimulated yielding a later peak around 6,h. In turn, insulin can normalize glucose. However, long-term dosing caused continuous hyperglycemia during and after infusion. Hyperinsulinemia was achieved during infusion, but diminished immediately after dosing despite the high glucose concentration. The effects of CST and MPL on glucose production were described with a competitive stimulation function. A disease progression model incorporating reduced endogenous glucose uptake/utilization was used to describe glucose metabolism under different treatments. The results exemplify the roles of endogenous and exogenous hormones in mediating glucose dynamics. The pharmacokinetic/pharmacodynamic model is valuable for quantitating diabetogenic effects of corticosteroid treatments and provides mechanistic insights into the hormonal control of the metabolic system. Copyright © 2009 John Wiley & Sons, Ltd. [source] Genome-wide expression analysis of iron regulation in Burkholderia pseudomallei and Burkholderia mallei using DNA microarraysFEMS MICROBIOLOGY LETTERS, Issue 2 2005Apichai Tuanyok Abstract Burkholderia pseudomallei and B. mallei are the causative agents of melioidosis and glanders, respectively. As iron regulation of gene expression is common in bacteria, in the present studies, we have used microarray analysis to examine the effects of growth in different iron concentrations on the regulation of gene expression in B. pseudomallei and B. mallei. Gene expression profiles for these two bacterial species were similar under high and low iron growth conditions irrespective of growth phase. Growth in low iron led to reduced expression of genes encoding most respiratory metabolic systems and proteins of putative function, such as NADH-dehydrogenases, cytochrome oxidases, and ATP-synthases. In contrast, genes encoding siderophore-mediated iron transport, heme-hemin receptors, and a variety of metabolic enzymes for alternative metabolism were induced under low iron conditions. The overall gene expression profiles suggest that B. pseudomallei and B. mallei are able to adapt to the iron-restricted conditions in the host environment by up-regulating an iron-acquisition system and by using alternative metabolic pathways for energy production. The observations relative to the induction of specific metabolic enzymes during bacterial growth under low iron conditions warrants further experimentation. [source] Genome-scale models of bacterial metabolism: reconstruction and applicationsFEMS MICROBIOLOGY REVIEWS, Issue 1 2009Maxime Durot Abstract Genome-scale metabolic models bridge the gap between genome-derived biochemical information and metabolic phenotypes in a principled manner, providing a solid interpretative framework for experimental data related to metabolic states, and enabling simple in silico experiments with whole-cell metabolism. Models have been reconstructed for almost 20 bacterial species, so far mainly through expert curation efforts integrating information from the literature with genome annotation. A wide variety of computational methods exploiting metabolic models have been developed and applied to bacteria, yielding valuable insights into bacterial metabolism and evolution, and providing a sound basis for computer-assisted design in metabolic engineering. Recent advances in computational systems biology and high-throughput experimental technologies pave the way for the systematic reconstruction of metabolic models from genomes of new species, and a corresponding expansion of the scope of their applications. In this review, we provide an introduction to the key ideas of metabolic modeling, survey the methods, and resources that enable model reconstruction and refinement, and chart applications to the investigation of global properties of metabolic systems, the interpretation of experimental results, and the re-engineering of their biochemical capabilities. [source] Inflammatory effects of nutritional stimuli: further support for the need for a big picture approach to tackling obesity and chronic diseaseOBESITY REVIEWS, Issue 2 2010G. Egger Summary The discovery of a form of low-grade systemic inflammation (called ,metaflammation'), and the close evolutionary link between the immune and metabolic systems, poses questions about the supposed antigens (inducers) of such an immune reaction. Initially, this was thought to be mediated through obesity. However, we have identified a number of lifestyle or environmentally related inducers that may cause metaflammation, even in the absence of obesity. In this paper, the third of a series linking obesity with broad environmental and evolutionary factors, we identify nutritional stimuli with evidence of an involvement in metaflammation. From this we propose that components of certain foods and beverages with which humans have not evolved, are more often the inducers of an inflammatory effect in the body than those with which humans have become more familiar, and to which a neutral, or anti-inflammatory response may be expected to have developed. The implications of such a finding are considered in relation to broader aspects of the environment, economic growth, policy change and current global financial issues. [source] Emergence and the Forms of CitiesARCHITECTURAL DESIGN, Issue 3 2010Michael Weinstock Abstract Michael Weinstock's significant new book The Architecture of Emergence: The Evolution of Form in Nature and Civilisation calls into question the received notion of culture. Rather than perceiving civilisation as intrinsically human or humanist, standing outside and beyond nature, Weinstock positions human development alongside ecological development: the history of cultural evolution and the production of cities are set in the context of processes and forms of the natural world. In this extract from Chapter 7, Weinstock charts how the proliferation of cities and systems of cities and their extended metabolic systems across the world were characterised by episodic and irregular expansions, consolidation, collapse and subsequent reorganisation. Copyright © 2010 John Wiley & Sons, Ltd. [source] A hybrid model of anaerobic E. coli GJT001: Combination of elementary flux modes and cybernetic variablesBIOTECHNOLOGY PROGRESS, Issue 5 2008Jin Il Kim Flux balance analysis (FBA) in combination with the decomposition of metabolic networks into elementary modes has provided a route to modeling cellular metabolism. It is dependent, however, on the availability of external fluxes such as substrate uptake or growth rate before estimates can become available of intracellular fluxes. The framework classically does not allow modeling of metabolic regulation or the formulation of dynamic models except through dynamic measurement of external fluxes. The cybernetic modeling approach of Ramkrishna and coworkers provides a dynamic framework for modeling metabolic systems because of its focus on describing regulatory processes based on cybernetic arguments and hence has the capacity to describe both external and internal fluxes. In this article, we explore the alternative of developing hybrid models combining cybernetic models for the external fluxes with the flux balance approach for estimation of the internal fluxes. The approach has the merit of the simplicity of the early cybernetic models and hence computationally facile while also providing detailed information on intracellular fluxes. The hybrid model of this article is based on elementary mode decomposition of the metabolic network. The uptake rates for the various elementary modes are combined using global cybernetic variables based on maximizing substrate uptake rates. Estimation of intracellular metabolism is based on its stoichiometric coupling with the external fluxes under the assumption of (pseudo-) steady state conditions. The set of parameters of the hybrid model was estimated with the aid of nonlinear optimization routine, by fitting simulations with dynamic experimental data on concentrations of biomass, substrate, and fermentation products. The hybrid model estimations were tested with FBA (based on measured substrate uptake rate) for two different metabolic networks (one is a reduced network which fixes ATP contribution to the biomass and maintenance requirement of ATP, and the other network is a more complex network which has a separate reaction for maintenance.) for the same experiment involving anaerobic growth of E. coli GJT001. The hybrid model estimated glucose consumption and all fermentation byproducts to better than 10%. The FBA makes similar estimations of fermentation products, however, with the exception of succinate. The simulation results show that the global cybernetic variables alone can regulate the metabolic reactions obtaining a very satisfactory fit to the measured fermentation byproducts. In view of the hybrid model's ability to predict biomass growth and fermentation byproducts of anaerobic E. coli GJT001, this reduced order model offers a computationally efficient alternative to more detailed models of metabolism and hence useful for the simulation of bioreactors. [source] | |||||||||||||