Inferring the metabolism of human orphan metabolites from their metabolic network context affirms human gluconokinase activity.

@article{Rolfsson2013InferringTM,
  title={Inferring the metabolism of human orphan metabolites from their metabolic network context affirms human gluconokinase activity.},
  author={{\'O}ttar Rolfsson and Giuseppe La Paglia and Manuela Magn{\'u}sd{\'o}ttir and Bernhard O. Palsson and Ines Thiele},
  journal={The Biochemical journal},
  year={2013},
  volume={449 2},
  pages={
          427-35
        }
}
Metabolic network reconstructions define metabolic information within a target organism and can therefore be used to address incomplete metabolic information. In the present study we used a computational approach to identify human metabolites whose metabolism is incomplete on the basis of their detection in humans but exclusion from the human metabolic network reconstruction RECON 1. Candidate solutions, composed of metabolic reactions capable of explaining the metabolism of these compounds… 

Figures from this paper

A community-driven global reconstruction of human metabolism

Recon 2, a community-driven, consensus 'metabolic reconstruction', is described, which is the most comprehensive representation of human metabolism that is applicable to computational modeling and has improved topological and functional features.

Biochemical Characterization of Human Gluconokinase and the Proposed Metabolic Impact of Gluconic Acid as Determined by Constraint Based Metabolic Network Analysis

The results indicate that significant metabolic flux changes in anabolic pathways linked to the hexose monophosphate shunt (HMS) are induced through a small increase in gluconate concentration, and argue that the enzyme takes part in a context specific carbon flux route into the HMS that, in humans, remains incompletely explored.

Comparative evaluation of open source software for mapping between metabolite identifiers in metabolic network reconstructions: application to Recon 2

Three applications developed for the metabolomics and chemical informatics communities were evaluated, finding that an InChI based application such as the Chemical Translation System was better suited to the task of mapping between metabolite identifiers in genome-scale metabolic reconstructions.

Sequence-based Network Completion Reveals the Integrality of Missing Reactions in Metabolic Networks*

To investigate whether functional networks existed where all gap-filling reactions were supported by sequence similarity to annotated enzymes, four draft networks were supplemented with all reactions from the Model SEED database for which minimal sequence similarity was found in their genomes.

Phenotypic differentiation of gastrointestinal microbes is reflected in their encoded metabolic repertoires

It is demonstrated that phenotypic differentiation within closely related species could be explained by their metabolic repertoire rather than their phylogenetic relationships, which has important implications in the understanding of the ecological and evolutionary complexity of the human gastrointestinal microbiome.

Biomedical applications of cell- and tissue-specific metabolic network models

Promise and Reality in the Expanding Field of Network Interaction Analysis: Metabolic Networks

The reconstruction of metabolic networks is presented, along with established and new algorithms to improve the description of cellular metabolism, and advantages and limitations of modeling algorithms and network reconstruction are discussed.

Constraint-based models predict metabolic and associated cellular functions

This work states that an increasing number of studies have recently combined models with high-throughput data sets for prospective experimentation, leading to validation of increasingly important and relevant biological predictions.

Confronting the catalytic dark matter encoded by sequenced genomes

It is estimated that >600 yeast and 2000 human proteins (>30% of their proteins of unknown function) are enzymes whose precise function remains(s) to be determined, illustrating the impressive scale of the ‘unknown enzyme problem’.

References

SHOWING 1-10 OF 60 REFERENCES

The human metabolic reconstruction Recon 1 directs hypotheses of novel human metabolic functions

It is shown that automatically generated solutions could produce biologically realistic hypotheses of novel human metabolic reactions such as of the fate of iduronic acid following glycan degradation and of N-acetylglutamate in amino acid metabolism.

Global reconstruction of the human metabolic network based on genomic and bibliomic data

The reconstruction process is described and it is demonstrated how the resulting genome-scale (or global) network can be used for the discovery of missing information, for the formulation of an in silico model, and as a structured context for analyzing high-throughput biological data sets.

Systematizing the generation of missing metabolic knowledge

Gap‐filling methods can be used to improve metabolic network models while simultaneously leading to discovery of new metabolic gene functions, as well as predict these missing reactions or genes likely to fill these knowledge gaps.

Filling gaps in a metabolic network using expression information

The MEP method is complementary to the sequence homology and genome context methods that are currently being used to identify missing metabolic genes and predicts over 20% of all known Saccharomyces cerevisiae metabolic enzyme-encoding genes within the top 50 out of 5594 candidates for their enzymatic function.

A compendium of inborn errors of metabolism mapped onto the human metabolic network.

It is found that carbohydrate, amino acid, and lipid metabolism were most affected by the IEMs, while the brain was the most commonly affected organ.

Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions

Numerous improvements to the i JO1366 metabolic reconstruction were suggested, including a new mechanism for growth on myo-inositol and several computational predictions should be experimentally verifiable by similar means.

Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighbours

A global framework that utilizes the pathway and (meta)genomic neighbour information to assign candidate sequences to orphan enzymes and was able to expand the models by on average 8%, with a considerable change in the flux connectivity patterns and improved essentiality prediction.

BiGG: a Biochemical Genetic and Genomic knowledgebase of large scale metabolic reconstructions

BiGG addresses a need in the systems biology community to have access to high quality curated metabolic models and reconstructions by integrating several published genome-scale metabolic networks into one resource with standard nomenclature.

A protocol for generating a high-quality genome-scale metabolic reconstruction

This protocol provides a helpful manual for all stages of the reconstruction process and presents a comprehensive protocol describing each step necessary to build a high-quality genome-scale metabolic reconstruction.

HMDB: the Human Metabolome Database

The Human Metabolome Database is designed to address the broad needs of biochemists, clinical chemists, physicians, medical geneticists, nutritionists and members of the metabolomics community.
...