Next Issue
Previous Issue

Table of Contents

Metabolites, Volume 2, Issue 1 (March 2012), Pages 1-291

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-15
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Comparative Chemistry of Aspergillus oryzae (RIB40) and A. flavus (NRRL 3357)
Metabolites 2012, 2(1), 39-56; doi:10.3390/metabo2010039
Received: 18 November 2011 / Revised: 14 December 2011 / Accepted: 22 December 2011 / Published: 5 January 2012
Cited by 19 | PDF Full-text (412 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aspergillus oryzae and A. flavus are important species in industrial biotechnology and food safety and have been some of the first aspergilli to be fully genome sequenced. Bioinformatic analysis has revealed 99.5% gene homology between the two species pointing towards a large coherence
[...] Read more.
Aspergillus oryzae and A. flavus are important species in industrial biotechnology and food safety and have been some of the first aspergilli to be fully genome sequenced. Bioinformatic analysis has revealed 99.5% gene homology between the two species pointing towards a large coherence in the secondary metabolite production. In this study we report on the first comparison of secondary metabolite production between the full genome sequenced strains of A. oryzae (RIB40) and A. flavus (NRRL 3357). Surprisingly, the overall chemical profiles of the two strains were mostly very different across 15 growth conditions. Contrary to previous studies we found the aflatrem precursor 13-desoxypaxilline to be a major metabolite from A. oryzae under certain growth conditions. For the first time, we additionally report A. oryzae to produce parasiticolide A and two new analogues hereof, along with four new alkaloids related to the A. flavus metabolites ditryptophenalines and miyakamides. Generally the secondary metabolite capability of A. oryzae presents several novel end products likely to result from the domestication process from A. flavus. Full article
(This article belongs to the Special Issue Secondary Metabolites and Metabolism)
Open AccessArticle Quantification of Signaling Lipids by Nano-Electrospray Ionization Tandem Mass Spectrometry (Nano-ESI MS/MS)
Metabolites 2012, 2(1), 57-76; doi:10.3390/metabo2010057
Received: 29 November 2011 / Revised: 4 January 2012 / Accepted: 6 January 2012 / Published: 16 January 2012
Cited by 13 | PDF Full-text (947 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lipids, such as phosphoinositides (PIPs) and diacylglycerol (DAG), are important signaling intermediates involved in cellular processes such as T cell receptor (TCR)-mediated signal transduction. Here we report identification and quantification of PIP, PIP2 and DAG from crude lipid extracts. Capitalizing on the
[...] Read more.
Lipids, such as phosphoinositides (PIPs) and diacylglycerol (DAG), are important signaling intermediates involved in cellular processes such as T cell receptor (TCR)-mediated signal transduction. Here we report identification and quantification of PIP, PIP2 and DAG from crude lipid extracts. Capitalizing on the different extraction properties of PIPs and DAGs allowed us to efficiently recover both lipid classes from one sample. Rapid analysis of endogenous signaling molecules was performed by nano-electrospray ionization tandem mass spectrometry (nano-ESI MS/MS), employing lipid class-specific neutral loss and multiple precursor ion scanning for their identification and quantification. Profiling of DAG, PIP and PIP2 molecular species in primary human T cells before and after TCR stimulation resulted in a two-fold increase in DAG levels with a shift towards 1-stearoyl-2-arachidonoyl-DAG in stimulated cells. PIP2 levels were slightly reduced, while PIP levels remained unchanged. Full article
(This article belongs to the Special Issue Lipidomics)
Open AccessArticle The Effect of LC-MS Data Preprocessing Methods on the Selection of Plasma Biomarkers in Fed vs. Fasted Rats
Metabolites 2012, 2(1), 77-99; doi:10.3390/metabo2010077
Received: 30 November 2011 / Revised: 6 January 2012 / Accepted: 6 January 2012 / Published: 18 January 2012
Cited by 22 | PDF Full-text (437 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The metabolic composition of plasma is affected by time passed since the last meal and by individual variation in metabolite clearance rates. Rat plasma in fed and fasted states was analyzed with liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF) for an untargeted investigation of
[...] Read more.
The metabolic composition of plasma is affected by time passed since the last meal and by individual variation in metabolite clearance rates. Rat plasma in fed and fasted states was analyzed with liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF) for an untargeted investigation of these metabolite patterns. The dataset was used to investigate the effect of data preprocessing on biomarker selection using three different softwares, MarkerLynxTM, MZmine, XCMS along with a customized preprocessing method that performs binning of m/z channels followed by summation through retention time. Direct comparison of selected features representing the fed or fasted state showed large differences between the softwares. Many false positive markers were obtained from custom data preprocessing compared with dedicated softwares while MarkerLynxTM provided better coverage of markers. However, marker selection was more reliable with the gap filling (or peak finding) algorithms present in MZmine and XCMS. Further identification of the putative markers revealed that many of the differences between the markers selected were due to variations in features representing adducts or daughter ions of the same metabolites or of compounds from the same chemical subclasses, e.g., lyso-phosphatidylcholines (LPCs) and lyso-phosphatidylethanolamines (LPEs). We conclude that despite considerable differences in the performance of the preprocessing tools we could extract the same biological information by any of them. Carnitine, branched-chain amino acids, LPCs and LPEs were identified by all methods as markers of the fed state whereas acetylcarnitine was abundant during fasting in rats. Full article
(This article belongs to the Special Issue Feature Papers)
Open AccessArticle Investigation of Phenolic Acids in Suspension Cultures of Vitis vinifera Stimulated with Indanoyl-Isoleucine, N-Linolenoyl-L-Glutamine, Malonyl Coenzyme A and Insect Saliva
Metabolites 2012, 2(1), 165-177; doi:10.3390/metabo2010165
Received: 19 December 2011 / Revised: 25 January 2012 / Accepted: 8 February 2012 / Published: 15 February 2012
Cited by 1 | PDF Full-text (494 KB) | HTML Full-text | XML Full-text
Abstract
Vitis vinifera c.v. Muscat de Frontignan (grape) contains various high valuable bioactive phenolic compounds with pharmaceutical properties and industrial interest which are not fully exploited. The focus of this investigation consists in testing the effects of various biological elicitors on a non-morphogenic callus
[...] Read more.
Vitis vinifera c.v. Muscat de Frontignan (grape) contains various high valuable bioactive phenolic compounds with pharmaceutical properties and industrial interest which are not fully exploited. The focus of this investigation consists in testing the effects of various biological elicitors on a non-morphogenic callus suspension culture of V. vinifera. The investigated elicitors: Indanoyl-isoleucine (IN), N-linolenoyl-L-glutamine (LG), insect saliva (IS) and malonyl coenzyme A (MCoA) were aimed at mimicking the influence of environmental pathogens on plants in their natural habitats and at provoking exogenous induction of the phenylpropanoid pathway. The elicitors’ indanoyl-isoleucine (IN), N-linolenoyl-L-glutamine (LG) and insect saliva (IS), as well as malonyl coenzyme A (MCoA), were independently inoculated to stimulate the synthesis of phenylpropanoids. All of the enhancers positively increased the concentration of phenolic compounds in grape cells. The highest concentration of phenolic acids was detected after 2 h for MCoA, after 48 h for IN and after 24 h for LG and IS respectively. At the maximum production time, treated grape cells had a 3.5-fold (MCoA), 1.6-fold (IN) and 1.5-fold (IS) higher phenolic acid content compared to the corresponding control samples. The HPLC results of grape cells showed two major resveratrol derivatives: 3-O-Glucosyl-resveratrol and 4-(3,5-dihydroxyphenyl)-phenol. Their influences of the different elicitors, time of harvest and biomass concentration (p < 0.0001) were statistically significant on the synthesis of phenolic compounds. The induction with MCoA was found to demonstrate the highest statistical effect corresponding to the strongest stress response within the phenylpropanoid pathway in grape cells. Full article
(This article belongs to the Special Issue Secondary Metabolites and Metabolism)
Open AccessArticle Intracellular Metabolite Pool Changes in Response to Nutrient Depletion Induced Metabolic Switching in Streptomyces coelicolor
Metabolites 2012, 2(1), 178-194; doi:10.3390/metabo2010178
Received: 15 December 2011 / Revised: 18 January 2012 / Accepted: 10 February 2012 / Published: 17 February 2012
Cited by 7 | PDF Full-text (1274 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A metabolite profiling study of the antibiotic producing bacterium Streptomyces coelicolor A3(2) has been performed. The aim of this study was to monitor intracellular metabolite pool changes occurring as strains of S. coelicolor react to nutrient depletion with metabolic re-modeling, so-called metabolic switching,
[...] Read more.
A metabolite profiling study of the antibiotic producing bacterium Streptomyces coelicolor A3(2) has been performed. The aim of this study was to monitor intracellular metabolite pool changes occurring as strains of S. coelicolor react to nutrient depletion with metabolic re-modeling, so-called metabolic switching, and transition from growth to secondary metabolite production phase. Two different culture media were applied, providing depletion of the key nutrients phosphate and L-glutamate, respectively, as the triggers for metabolic switching. Targeted GC-MS and LC-MS methods were employed to quantify important primary metabolite groups like amino acids, organic acids, sugar phosphates and other phosphorylated metabolites, and nucleotides in time-course samples withdrawn from fully-controlled batch fermentations. A general decline, starting already in the early growth phase, was observed for nucleotide pools and phosphorylated metabolite pools for both the phosphate and glutamate limited cultures. The change in amino acid and organic acid pools were more scattered, especially in the phosphate limited situation while a general decrease in amino acid and non-amino organic acid pools was observed in the L-glutamate limited situation. A phoP deletion mutant showed basically the same metabolite pool changes as the wild-type strain M145 when cultivated on phosphate limited medium. This implies that the inactivation of the phoP gene has only little effect on the detected metabolite levels in the cell. The energy charge was found to be relatively constant during growth, transition and secondary metabolite production phase. The results of this study and the employed targeted metabolite profiling methodology are directly relevant for the evaluation of precursor metabolite and energy supply for both natural and heterologous production of secondary metabolites in S. coelicolor. Full article
(This article belongs to the Special Issue Secondary Metabolites and Metabolism)
Open AccessArticle Shotgun Lipidomics by Sequential Precursor Ion Fragmentation on a Hybrid Quadrupole Time-of-Flight Mass Spectrometer
Metabolites 2012, 2(1), 195-213; doi:10.3390/metabo2010195
Received: 24 December 2011 / Revised: 10 February 2012 / Accepted: 13 February 2012 / Published: 20 February 2012
Cited by 26 | PDF Full-text (3041 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Shotgun lipidomics has evolved into a myriad of multi-dimensional strategies for molecular lipid characterization, including bioinformatics tools for mass spectrum interpretation and quantitative measurements to study systems-lipidomics in complex biological extracts. Taking advantage of spectral mass accuracy, scan speed and sensitivity of improved
[...] Read more.
Shotgun lipidomics has evolved into a myriad of multi-dimensional strategies for molecular lipid characterization, including bioinformatics tools for mass spectrum interpretation and quantitative measurements to study systems-lipidomics in complex biological extracts. Taking advantage of spectral mass accuracy, scan speed and sensitivity of improved quadrupole linked time-of-flight mass analyzers, we developed a bias-free global lipid profiling acquisition technique of sequential precursor ion fragmentation called MS/MSALL. This generic information-independent tandem mass spectrometry (MS) technique consists of a Q1 stepped mass isolation window through a set mass range in small increments, fragmenting and recording all product ions and neutral losses. Through the accurate MS and MS/MS information, the molecular lipid species are resolved, including distinction of isobaric and isomeric species, and composed into more precise lipidomic outputs. The method demonstrates good reproducibility and at least 3 orders of dynamic quantification range for isomeric ceramides in human plasma. More than 400 molecular lipids in human plasma were uncovered and quantified in less than 12 min, including acquisitions in both positive and negative polarity modes. We anticipate that the performance of sequential precursor ion fragmentation both in quality and throughput will lead to the uncovering of new avenues throughout the biomedical research community, enhance biomarker discovery and provide novel information target discovery programs as it will prospectively shed new insight into affected metabolic and signaling pathways. Full article
(This article belongs to the Special Issue Lipidomics)
Figures

Open AccessArticle Atlantinone A, a Meroterpenoid Produced by Penicillium ribeum and Several Cheese Associated Penicillium Species
Metabolites 2012, 2(1), 214-220; doi:10.3390/metabo2010214
Received: 7 November 2011 / Revised: 30 December 2011 / Accepted: 10 February 2012 / Published: 23 February 2012
Cited by 4 | PDF Full-text (415 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Atlantinone A has been isolated from the psychrotolerant fungus Penicillium ribeum. The exact structure of the compound was confirmed by mass spectrometric and 1- and 2D NMR experiments. Atlantinone A was originally only produced upon chemical epigenetic manipulation of P. hirayamae,
[...] Read more.
Atlantinone A has been isolated from the psychrotolerant fungus Penicillium ribeum. The exact structure of the compound was confirmed by mass spectrometric and 1- and 2D NMR experiments. Atlantinone A was originally only produced upon chemical epigenetic manipulation of P. hirayamae, however in this study the compound was found to be produced at standard growth conditions by the following species; P. solitum, P. discolor, P. commune, P. caseifulvum, P. palitans, P. novae-zeelandiae and P. monticola. A biosynthetic pathway to atlantinone A starting from andrastin A is proposed. Full article
(This article belongs to the Special Issue Secondary Metabolites and Metabolism)
Open AccessArticle Canonical Modeling of the Multi-Scale Regulation of the Heat Stress Response in Yeast
Metabolites 2012, 2(1), 221-241; doi:10.3390/metabo2010221
Received: 30 December 2011 / Revised: 8 February 2012 / Accepted: 10 February 2012 / Published: 27 February 2012
Cited by 5 | PDF Full-text (360 KB) | HTML Full-text | XML Full-text
Abstract
Heat is one of the most fundamental and ancient environmental stresses, and response mechanisms are found in prokaryotes and shared among most eukaryotes. In the budding yeast Saccharomyces cerevisiae, the heat stress response involves coordinated changes at all biological levels, from gene
[...] Read more.
Heat is one of the most fundamental and ancient environmental stresses, and response mechanisms are found in prokaryotes and shared among most eukaryotes. In the budding yeast Saccharomyces cerevisiae, the heat stress response involves coordinated changes at all biological levels, from gene expression to protein and metabolite abundances, and to temporary adjustments in physiology. Due to its integrative multi-level-multi-scale nature, heat adaptation constitutes a complex dynamic process, which has forced most experimental and modeling analyses in the past to focus on just one or a few of its aspects. Here we review the basic components of the heat stress response in yeast and outline what has been done, and what needs to be done, to merge the available information into computational structures that permit comprehensive diagnostics, interrogation, and interpretation. We illustrate the process in particular with the coordination of two metabolic responses, namely the dramatic accumulation of the protective disaccharide trehalose and the substantial change in the profile of sphingolipids, which in turn affect gene expression. The proposed methods primarily use differential equations in the canonical modeling framework of Biochemical Systems Theory (BST), which permits the relatively easy construction of coarse, initial models even in systems that are incompletely characterized. Full article
(This article belongs to the Special Issue Metabolic Network Models)
Open AccessArticle Comparative Lipidomic Profiling of S. cerevisiae and Four Other Hemiascomycetous Yeasts
Metabolites 2012, 2(1), 254-267; doi:10.3390/metabo2010254
Received: 19 January 2012 / Revised: 23 February 2012 / Accepted: 24 February 2012 / Published: 2 March 2012
Cited by 2 | PDF Full-text (528 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Glycerophospholipids (GP) are the building blocks of cellular membranes and play essential roles in cell compartmentation, membrane fluidity or apoptosis. In addition, GPs are sources for multifunctional second messengers. Whereas the genome and proteome of the most intensively studied eukaryotic model organism, the
[...] Read more.
Glycerophospholipids (GP) are the building blocks of cellular membranes and play essential roles in cell compartmentation, membrane fluidity or apoptosis. In addition, GPs are sources for multifunctional second messengers. Whereas the genome and proteome of the most intensively studied eukaryotic model organism, the baker’s yeast (Saccharomyces cerevisiae), are well characterized, the analysis of its lipid composition is still at the beginning. Moreover, different yeast species can be distinguished on the DNA, RNA and protein level, but it is currently unknown if they can also be differentiated by determination of their GP pattern. Therefore, the GP compositions of five different yeast strains, grown under identical environmental conditions, were elucidated using high performance liquid chromatography coupled to negative electrospray ionization-hybrid linear ion trap-Fourier transform ion cyclotron resonance mass spectrometry in single and multistage mode. Using this approach, relative quantification of more than 100 molecular species belonging to nine GP classes was achieved. The comparative lipidomic profiling of Saccharomyces cerevisiae, Saccharomyces bayanus, Kluyveromyces thermotolerans, Pichia angusta, and Yarrowia lipolytica revealed characteristic GP profiles for each strain. However, genetically related yeast strains show similarities in their GP compositions, e.g., Saccharomyces cerevisiae and Saccharomyces bayanus. Full article
(This article belongs to the Special Issue Lipidomics)
Figures

Review

Jump to: Research

Open AccessReview Perturbations of Lipid Metabolism Indexed by Lipidomic Biomarkers
Metabolites 2012, 2(1), 1-18; doi:10.3390/metabo2010001
Received: 28 November 2011 / Revised: 21 December 2011 / Accepted: 22 December 2011 / Published: 4 January 2012
Cited by 3 | PDF Full-text (509 KB) | HTML Full-text | XML Full-text
Abstract
The lipidome of the liver and the secreted circulating lipoproteins can now be interrogated conveniently by automated mass spectrometric methods. Multivariate analysis of the liver and serum lipid composition in various animal modes or in human patients has pointed to specific molecular species
[...] Read more.
The lipidome of the liver and the secreted circulating lipoproteins can now be interrogated conveniently by automated mass spectrometric methods. Multivariate analysis of the liver and serum lipid composition in various animal modes or in human patients has pointed to specific molecular species markers. The perturbations of lipid metabolism can be categorized on the basis of three basic pathological mechanisms: (1) an accelerated rate of de novo lipogenesis; (2) perturbation of the peroxisome pathway of ether-lipid and very-long-chain fatty acid biosynthesis; (3) a change in the rate of interconversion of essential omega-3 and -6 polyunsaturated fatty acids. This review provides examples to illustrate the practicalities of lipidomic studies in biomedicine. Full article
(This article belongs to the Special Issue Lipidomics)
Open AccessReview Mass Spectrometry Based Lipidomics: An Overview of Technological Platforms
Metabolites 2012, 2(1), 19-38; doi:10.3390/metabo2010019
Received: 23 November 2011 / Revised: 22 December 2011 / Accepted: 24 December 2011 / Published: 5 January 2012
Cited by 30 | PDF Full-text (411 KB) | HTML Full-text | XML Full-text
Abstract
One decade after the genomic and the proteomic life science revolution, new ‘omics’ fields are emerging. The metabolome encompasses the entity of small molecules—Most often end products of a catalytic process regulated by genes and proteins—with the lipidome being its fat soluble subdivision.
[...] Read more.
One decade after the genomic and the proteomic life science revolution, new ‘omics’ fields are emerging. The metabolome encompasses the entity of small molecules—Most often end products of a catalytic process regulated by genes and proteins—with the lipidome being its fat soluble subdivision. Within recent years, lipids are more and more regarded not only as energy storage compounds but also as interactive players in various cellular regulation cycles and thus attain rising interest in the bio-medical community. The field of lipidomics is, on one hand, fuelled by analytical technology advances, particularly mass spectrometry and chromatography, but on the other hand new biological questions also drive analytical technology developments. Compared to fairly standardized genomic or proteomic high-throughput protocols, the high degree of molecular heterogeneity adds a special analytical challenge to lipidomic analysis. In this review, we will take a closer look at various mass spectrometric platforms for lipidomic analysis. We will focus on the advantages and limitations of various experimental setups like ‘shotgun lipidomics’, liquid chromatography—Mass spectrometry (LC-MS) and matrix assisted laser desorption ionization-time of flight (MALDI-TOF) based approaches. We will also examine available software packages for data analysis, which nowadays is in fact the rate limiting step for most ‘omics’ workflows. Full article
(This article belongs to the Special Issue Lipidomics)
Open AccessReview Genetics of Polyketide Metabolism in Aspergillus nidulans
Metabolites 2012, 2(1), 100-133; doi:10.3390/metabo2010100
Received: 1 November 2011 / Revised: 23 December 2011 / Accepted: 17 January 2012 / Published: 30 January 2012
Cited by 6 | PDF Full-text (1121 KB) | HTML Full-text | XML Full-text
Abstract
Secondary metabolites are small molecules that show large structural diversity and a broad range of bioactivities. Some metabolites are attractive as drugs or pigments while others act as harmful mycotoxins. Filamentous fungi have the capacity to produce a wide array of secondary metabolites
[...] Read more.
Secondary metabolites are small molecules that show large structural diversity and a broad range of bioactivities. Some metabolites are attractive as drugs or pigments while others act as harmful mycotoxins. Filamentous fungi have the capacity to produce a wide array of secondary metabolites including polyketides. The majority of genes required for production of these metabolites are mostly organized in gene clusters, which often are silent or barely expressed under laboratory conditions, making discovery and analysis difficult. Fortunately, the genome sequences of several filamentous fungi are publicly available, greatly facilitating the establishment of links between genes and metabolites. This review covers the attempts being made to trigger the activation of polyketide metabolism in the fungal model organism Aspergillus nidulans. Moreover, it will provide an overview of the pathways where ten polyketide synthase genes have been coupled to polyketide products. Therefore, the proposed biosynthesis of the following metabolites will be presented; naphthopyrone, sterigmatocystin, aspyridones, emericellamides, asperthecin, asperfuranone, monodictyphenone/emodin, orsellinic acid, and the austinols. Full article
(This article belongs to the Special Issue Secondary Metabolites and Metabolism)
Open AccessReview Lipidomics of Glycosphingolipids
Metabolites 2012, 2(1), 134-164; doi:10.3390/metabo2010134
Received: 28 November 2011 / Revised: 27 January 2012 / Accepted: 30 January 2012 / Published: 2 February 2012
Cited by 7 | PDF Full-text (484 KB) | HTML Full-text | XML Full-text
Abstract
Glycosphingolipids (GSLs) contain one or more sugars that are attached to a sphingolipid moiety, usually to a ceramide, but in rare cases also to a sphingoid base. A large structural heterogeneity results from differences in number, identity, linkage, and anomeric configuration of the
[...] Read more.
Glycosphingolipids (GSLs) contain one or more sugars that are attached to a sphingolipid moiety, usually to a ceramide, but in rare cases also to a sphingoid base. A large structural heterogeneity results from differences in number, identity, linkage, and anomeric configuration of the carbohydrate residues, and also from structural differences within the hydrophobic part. GSLs form complex cell-type specific patterns, which change with the species, the cellular differentiation state, viral transformation, ontogenesis, and oncogenesis. Although GSL structures can be assigned to only a few series with a common carbohydrate core, their structural variety and the complex pattern are challenges for their elucidation and quantification by mass spectrometric techniques. We present a general overview of the application of lipidomics for GSL determination. This includes analytical procedures and instrumentation together with recent correlations of GSL molecular species with human diseases. Difficulties such as the structural complexity and the lack of standard substances for complex GSLs are discussed. Full article
(This article belongs to the Special Issue Lipidomics)
Figures

Open AccessReview Human Metabolic Network: Reconstruction, Simulation, and Applications in Systems Biology
Metabolites 2012, 2(1), 242-253; doi:10.3390/metabo2010242
Received: 30 January 2012 / Revised: 18 February 2012 / Accepted: 27 February 2012 / Published: 2 March 2012
Cited by 4 | PDF Full-text (371 KB) | HTML Full-text | XML Full-text
Abstract
Metabolism is crucial to cell growth and proliferation. Deficiency or alterations in metabolic functions are known to be involved in many human diseases. Therefore, understanding the human metabolic system is important for the study and treatment of complex diseases. Current reconstructions of the
[...] Read more.
Metabolism is crucial to cell growth and proliferation. Deficiency or alterations in metabolic functions are known to be involved in many human diseases. Therefore, understanding the human metabolic system is important for the study and treatment of complex diseases. Current reconstructions of the global human metabolic network provide a computational platform to integrate genome-scale information on metabolism. The platform enables a systematic study of the regulation and is applicable to a wide variety of cases, wherein one could rely on in silico perturbations to predict novel targets, interpret systemic effects, and identify alterations in the metabolic states to better understand the genotype-phenotype relationships. In this review, we describe the reconstruction of the human metabolic network, introduce the constraint based modeling approach to analyze metabolic networks, and discuss systems biology applications to study human physiology and pathology. We highlight the challenges and opportunities in network reconstruction and systems modeling of the human metabolic system. Full article
(This article belongs to the Special Issue Metabolic Network Models)
Open AccessReview Stoichiometry Based Steady-State Hepatic Flux Analysis: Computational and Experimental Aspects
Metabolites 2012, 2(1), 268-291; doi:10.3390/metabo2010268
Received: 15 February 2012 / Revised: 5 March 2012 / Accepted: 6 March 2012 / Published: 14 March 2012
Cited by 2 | PDF Full-text (247 KB) | HTML Full-text | XML Full-text
Abstract
The liver has many complex physiological functions, including lipid, protein and carbohydrate metabolism, as well as bile and urea production. It detoxifies toxic substances and medicinal products. It also plays a key role in the onset and maintenance of abnormal metabolic patterns associated
[...] Read more.
The liver has many complex physiological functions, including lipid, protein and carbohydrate metabolism, as well as bile and urea production. It detoxifies toxic substances and medicinal products. It also plays a key role in the onset and maintenance of abnormal metabolic patterns associated with various disease states, such as burns, infections and major traumas. Liver cells have been commonly used in in vitro experiments to elucidate the toxic effects of drugs and metabolic changes caused by aberrant metabolic conditions, and to improve the functions of existing systems, such as bioartificial liver. More recently, isolated liver perfusion systems have been increasingly used to characterize intrinsic metabolic changes in the liver caused by various perturbations, including systemic injury, hepatotoxin exposure and warm ischemia. Metabolic engineering tools have been widely applied to these systems to identify metabolic flux distributions using metabolic flux analysis or flux balance analysis and to characterize the topology of the networks using metabolic pathway analysis. In this context, hepatic metabolic models, together with experimental methodologies where hepatocytes or perfused livers are mainly investigated, are described in detail in this review. The challenges and opportunities are also discussed extensively. Full article
(This article belongs to the Special Issue Metabolic Network Models)

Journal Contact

MDPI AG
Metabolites Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
metabolites@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Metabolites
Back to Top