scholarly journals Rewiring and regulation of cross-compartmentalized metabolism in protists

2010 ◽  
Vol 365 (1541) ◽  
pp. 831-845 ◽  
Author(s):  
Michael L. Ginger ◽  
Geoffrey I. McFadden ◽  
Paul A. M. Michels
Keyword(s):  
Metabolic Pathways ◽  
Carbon Flux ◽  
Isoprenoid Biosynthesis ◽  
Metabolic Diversity ◽  
Unicellular Eukaryotes ◽  
Metabolic Functions ◽  
Pathway Regulation ◽  
Casual Observer ◽  
Anabolic Pathway ◽  
Core Metabolism

Plastid acquisition, endosymbiotic associations, lateral gene transfer, organelle degeneracy or even organelle loss influence metabolic capabilities in many different protists. Thus, metabolic diversity is sculpted through the gain of new metabolic functions and moderation or loss of pathways that are often essential in the majority of eukaryotes. What is perhaps less apparent to the casual observer is that the sub-compartmentalization of ubiquitous pathways has been repeatedly remodelled during eukaryotic evolution, and the textbook pictures of intermediary metabolism established for animals, yeast and plants are not conserved in many protists. Moreover, metabolic remodelling can strongly influence the regulatory mechanisms that control carbon flux through the major metabolic pathways. Here, we provide an overview of how core metabolism has been reorganized in various unicellular eukaryotes, focusing in particular on one near universal catabolic pathway (glycolysis) and one ancient anabolic pathway (isoprenoid biosynthesis). For the example of isoprenoid biosynthesis, the compartmentalization of this process in protists often appears to have been influenced by plastid acquisition and loss, whereas for glycolysis several unexpected modes of compartmentalization have emerged. Significantly, the example of trypanosomatid glycolysis illustrates nicely how mathematical modelling and systems biology can be used to uncover or understand novel modes of pathway regulation.

scholarly journals Nucleus-Encoded Genes for Plastid-Targeted Proteins in Helicosporidium: Functional Diversity of a Cryptic Plastid in a Parasitic Alga

2004 ◽  
Vol 3 (5) ◽  
pp. 1198-1205 ◽  
Author(s):  
Audrey P. de Koning ◽  
Patrick J. Keeling
Keyword(s):  
Metabolic Pathways ◽  
Expressed Sequence Tag ◽  
Metabolic Adaptation ◽  
Metabolic Diversity ◽  
Leucine Biosynthesis ◽  
Metabolic Functions ◽  
Transit Peptides ◽  
Evolutionary Trajectories ◽  
Expressed Sequence ◽  
Independent Transformation

ABSTRACT Plastids are the organelles of plants and algae that house photosynthesis and many other biochemical pathways. Plastids contain a small genome, but most of their proteins are encoded in the nucleus and posttranslationally targeted to the organelle. When plants and algae lose photosynthesis, they virtually always retain a highly reduced “cryptic” plastid. Cryptic plastids are known to exist in many organisms, although their metabolic functions are seldom understood. The best-studied example of a cryptic plastid is from the intracellular malaria parasite, Plasmodium, which has retained a plastid for the biosynthesis of fatty acids, isoprenoids, and heme by the use of plastid-targeted enzymes. To study a completely independent transformation of a photosynthetic plastid to a cryptic plastid in another alga-turned-parasite, we conducted an expressed sequence tag (EST) survey of Helicosporidium. This parasite has recently been recognized as a highly derived green alga. Based on phylogenetic relationships to other plastid homologues and the presence of N-terminal transit peptides, we have identified 20 putatively plastid-targeted enzymes that are involved in a wide variety of metabolic pathways. Overall, the metabolic diversity of the Helicosporidium cryptic plastid exceeds that of the Plasmodium plastid, as it includes representatives of most of the pathways known to operate in the Plasmodium plastid as well as many others. In particular, several amino acid biosynthetic pathways have been retained, including the leucine biosynthesis pathway, which was only recently recognized in plant plastids. These two parasites represent different evolutionary trajectories in plastid metabolic adaptation.

scholarly journals Phylogenetic and metabolic diversity have contrasting effects on the ecological functioning of bacterial communities

2021 ◽  
Vol 97 (3) ◽  
Author(s):  
Constantinos Xenophontos ◽  
Martin Taubert ◽  
W Stanley Harpole ◽  
Kirsten Küsel
Keyword(s):  
Bacterial Communities ◽  
Species Interactions ◽  
Phylogenetic Diversity ◽  
Molecular Mechanisms ◽  
Linear Models ◽  
Theory Development ◽  
Metabolic Diversity ◽  
Community Functioning ◽  
Metabolic Functions ◽  
Independent Effects

ABSTRACT Quantifying the relative contributions of microbial species to ecosystem functioning is challenging, because of the distinct mechanisms associated with microbial phylogenetic and metabolic diversity. We constructed bacterial communities with different diversity traits and employed exoenzyme activities (EEAs) and carbon acquisition potential (CAP) from substrates as proxies of bacterial functioning to test the independent effects of these two aspects of biodiversity. We expected that metabolic diversity, but not phylogenetic diversity would be associated with greater ecological function. Phylogenetically relatedness should intensify species interactions and coexistence, therefore amplifying the influence of metabolic diversity. We examined the effects of each diversity treatment using linear models, while controlling for the other, and found that phylogenetic diversity strongly influenced community functioning, positively and negatively. Metabolic diversity, however, exhibited negative or non-significant relationships with community functioning. When controlling for different substrates, EEAs increased along with phylogenetic diversity but decreased with metabolic diversity. The strength of diversity effects was related to substrate chemistry and the molecular mechanisms associated with each substrate's degradation. EEAs of phylogenetically similar groups were strongly affected by within-genus interactions. These results highlight the unique flexibility of microbial metabolic functions that must be considered in further ecological theory development.

Abstract 241: Acetylomic and Metabolomic Alterations in Aged Hearts: Role for Silent Information Regulator (SIRT) 3

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jimmy Zhang ◽  
William R Urciuoli ◽  
Paul S Brookes ◽  
George A Porter ◽  
Sergiy M Nadtochiy
Keyword(s):  
Metabolic Pathways ◽  
Carbon Flux ◽  
Tca Cycle ◽  
Adult Group ◽  
Protein Levels ◽  
Mitochondrial Alterations ◽  
Age Related ◽  
Transport Chain ◽  
Tca Cycle Intermediates ◽  
Substantial Decline

Introduction: SIRT3 is a mitochondrial metabolic regulator, and a decline in function of SIRT3 may play a role in age-related mitochondrial alterations. The aim of this study was to investigate the possible down-regulation of SIRT3 activity in aged hearts, and to identify which metabolic pathways in aged hearts may be impaired due to SIRT3 dysfunction. Methods: Mitochondria were isolated from WT adult (7 mo.), SIRT3 -/- adult (7 mo.) and WT aged (18 mo.) hearts. Acetylated proteins in mitochondrial samples were identified using 2D gels and mass spectrometry. Metabolite concentrations and carbon fluxes through core metabolic pathways were determined using 13 C-labeled substrates and LC-MS/MS. Results: Mitochondrial acetylation patterns in the SIRT3 -/- adult group matched those found in the WT aged group; the level of acetylation was significantly higher than in WT adult. While the SIRT3 -/- samples exhibited zero SIRT3 protein content, no difference in SIRT3 protein level was seen between adult and aged WT hearts. Mechanistically, this suggests that alterations in mitochondrial acetylation during aging were not caused by lower SIRT3 protein levels, but rather by a lower SIRT3 enzymatic activity. Furthermore, aged myocardium exhibited 40% lower NAD + levels, which may underlie compromised SIRT3 activity. ATP levels were decreased in both SIRT3 -/- and WT aged hearts, suggesting possible defects in energy metabolism. Using metabolomics, we demonstrated that alterations of TCA cycle intermediates were similar in SIRT3 -/- and WT aged hearts (relative to WT adult), and included a substantial decline of carbon flux through α-ketoglutarate and malate. Furthermore, regulation of energy production might also be impaired at the level of the electron transport chain, where Complex I was significantly inhibited in both SIRT3 deficient and aged hearts. Conclusions: Collectively these data suggested that acetylomic and metabolomic fingerprints observed in SIRT3 -/- hearts were recapitulated in aged hearts.

scholarly journals Carbon-flux distribution in the central metabolic pathways of Corynebacterium glutamicum during growth on fructose

1998 ◽  
Vol 254 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Helene Dominguez ◽  
Catherine Rollin ◽  
Armel Guyonvarch ◽  
Jean-Luc Guerquin-Kern ◽  
Muriel Cocaign-Bousquet ◽  
...  
Keyword(s):  
Corynebacterium Glutamicum ◽  
Metabolic Pathways ◽  
Carbon Flux ◽  
Flux Distribution ◽  
Carbon Flux Distribution

scholarly journals Core Metabolism Shifts during Growth on Methanol versus Methane in the Methanotroph Methylomicrobium buryatense 5GB1

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Yanfen Fu ◽  
Lian He ◽  
Jennifer Reeve ◽  
David A. C. Beck ◽  
Mary E. Lidstrom
Keyword(s):  
Flux Balance Analysis ◽  
Metabolic Pathways ◽  
Scale Model ◽  
Obligate Methylotroph ◽  
Content Type ◽  
Advantages And Disadvantages ◽  
The Core ◽  
Flux Balance ◽  
Balance Analysis ◽  
Core Metabolism

ABSTRACT Methylomicrobium buryatense 5GB1 is an obligate methylotroph which grows on methane or methanol with similar growth rates. It has long been assumed that the core metabolic pathways must be similar on the two substrates, but recent studies of methane metabolism in this bacterium suggest that growth on methanol might have significant differences from growth on methane. In this study, both a targeted metabolomics approach and a 13C tracer approach were taken to understand core carbon metabolism in M. buryatense 5GB1 during growth on methanol and to determine whether such differences occur. Our results suggest a systematic shift of active core metabolism in which increased flux occurred through both the Entner-Doudoroff (ED) pathway and the partial serine cycle, while the tricarboxylic acid (TCA) cycle was incomplete, in contrast to growth on methane. Using the experimental results as constraints, we applied flux balance analysis to determine the metabolic flux phenotype of M. buryatense 5GB1 growing on methanol, and the results are consistent with predictions based on ATP and NADH changes. Transcriptomics analysis suggested that the changes in fluxes and metabolite levels represented results of posttranscriptional regulation. The combination of flux balance analysis of the genome-scale model and the flux ratio from 13C data changed the solution space for a better prediction of cell behavior and demonstrated the significant differences in physiology between growth on methane and growth on methanol. IMPORTANCE One-carbon compounds such as methane and methanol are of increasing interest as sustainable substrates for biological production of fuels and industrial chemicals. The bacteria that carry out these conversions have been studied for many decades, but gaps exist in our knowledge of their metabolic pathways. One such gap is the difference between growth on methane and growth on methanol. Understanding such metabolism is important, since each has advantages and disadvantages as a feedstock for production of chemicals and fuels. The significance of our research is in the demonstration that the metabolic network is substantially altered in each case and in the delineation of these changes. The resulting new insights into the core metabolism of this bacterium now provide an improved basis for future strain design.

scholarly journals Metabolite transport across the peroxisomal membrane

2006 ◽  
Vol 401 (2) ◽  
pp. 365-375 ◽  
Author(s):  
Wouter F. Visser ◽  
Carlo W. T. van Roermund ◽  
Lodewijk Ijlst ◽  
Hans R. Waterham ◽  
Ronald J. A. Wanders
Keyword(s):  
Fatty Acid ◽  
Metabolic Pathways ◽  
Adenine Nucleotides ◽  
Transport Systems ◽  
Peroxisomal Membrane ◽  
Metabolite Transport ◽  
Metabolic Functions ◽  
Current State ◽  
Made In

In recent years, much progress has been made with respect to the unravelling of the functions of peroxisomes in metabolism, and it is now well established that peroxisomes are indispensable organelles, especially in higher eukaryotes. Peroxisomes catalyse a number of essential metabolic functions including fatty acid β-oxidation, ether phospholipid biosynthesis, fatty acid α-oxidation and glyoxylate detoxification. The involvement of peroxisomes in these metabolic pathways necessitates the transport of metabolites in and out of peroxisomes. Recently, considerable progress has been made in the characterization of metabolite transport across the peroxisomal membrane. Peroxisomes posses several specialized transport systems to transport metabolites. This is exemplified by the identification of a specific transporter for adenine nucleotides and several half-ABC (ATP-binding cassette) transporters which may be present as hetero- and homo-dimers. The nature of the substrates handled by the different ABC transporters is less clear. In this review we will describe the current state of knowledge of the permeability properties of the peroxisomal membrane.

scholarly journals Metabolomic Interactions: An Insight into Health and Disease

2021 ◽  
pp. 61-67
Author(s):  
Maheswara Reddy Mallu ◽  
Shaik Mohammad Anjum ◽  
Sai Sri Samyutha Katravulapalli ◽  
Sri Sai Priya Avuthu ◽  
Koteswara Reddy Gujjula ◽  
...  
Keyword(s):  
Metabolic Engineering ◽  
Human Body ◽  
Metabolic Pathways ◽  
Biological Processes ◽  
Therapeutic Treatment ◽  
The Past ◽  
Metabolic Functions ◽  
Health And Disease ◽  
Metabolic Reactions ◽  
Insight Into

Over the past decade, metabolic engineering has emerged as an active and distinct discipline characterized by its over-arching emphasis on integration. In practice, metabolic engineering is the directed improvement of cellular properties through the application of modern genetic methods. The concept of metabolic regulations deals with the varied and innumerable metabolic pathways that are present in the human body. A combination of such metabolic reactions paves the way to the proper functioning of different physiological and biological processes. Dealing with the adversities of a disease, engineering of novel metabolic pathways showcases the potential of metabolic engineering and its application in the therapeutic treatment of diseases. A proper and deeper understanding of the metabolic functions in the human body can be known from simulated yeast models. This review gives a brief understanding about the interactions between the molecular set of metabolome and its complexity.

scholarly journals Host-bacteria metabolic crosstalk drives S. aureus biofilm

2021 ◽  
Vol 8 (6) ◽  
pp. 106-107
Author(s):  
Kira L. Tomlinson ◽  
Sebastián A. Riquelme
Keyword(s):  
Metabolic Pathways ◽  
Carbon Flux ◽  
Immune Cell ◽  
Oxidant Stress ◽  
Bacterial Survival ◽  
Cell Recruitment ◽  
Biofilm Production ◽  
Lung Infections ◽  
Immune Cell Recruitment

Staphylococcus aureus is a prominent pathogen that can cause intractable lung infections in humans. S. aureus persists in the airway despite inflammation and immune cell recruitment by adapting to host-derived antimicrobial factors. A key component of the immune response to infection are host metabolites that regulate inflammation and bacterial survival. In our recent paper (Tomlinson et al., Nat Commun, doi: 10.1038/s41467-021-21718-y), we demonstrated that S. aureus induces the production of the immunoreglatory metabolite itaconate in airway immune cells by stimulating mitochondrial oxidant stress. Itaconate in turn inhibited S. aureus glycolysis and growth, and promoted carbon flux through bacterial metabolic pathways that support biofilm production. These itaconate-induced metabolic changes were recapitulated in a longitudinal series of clinical isolates from a patient with chronic staphylococcal lung infections, demonstrating a role for host immunometabolism in driving bacterial persistence during long-term staphylococcal lung infections.

scholarly journals A Study of the Short and Long-term Regulation of E. coli Metabolic Pathways

2011 ◽  
Vol 8 (3) ◽  
pp. 195-209 ◽  
Author(s):  
Anália Lourenço ◽  
Sónia Carneiro ◽  
José P. Pinto ◽  
Miguel Rocha ◽  
Eugénio C. Ferreira ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Control Cell ◽  
E Coli ◽  
Cell Responses ◽  
Metabolic Functions ◽  
Enzymatic Regulation ◽  
Short And Long Term ◽  
Metabolic Activities ◽  
And Control

Summary The present study addresses the regulatory network of Escherichia coli and offers a global view of the short- and long-term regulation of its metabolic pathways. The regulatory mechanisms responsible for key metabolic activities and the structure behind such mechanisms are detailed. Most metabolic functions are dependent on the activity of transcriptional regulators over gene expression - the so-called long-term regulation. However, enzymatic regulation - the so-called short-term regulation - often overlays transcriptional regulation and even, in particular metabolic pathways, enzymatic regulation may prevail. As such, understanding the balance between these two types of regulation is necessary to be able to predict and control cell responses, specifically cell responses to the various environmental stresses.

Sign in / Sign up

Export Citation Format

Share Document