Dataset Information

Smallbone2013 - Human metabolism global reconstruction (recon 2.1)

ABSTRACT: Smallbone2013 - Human metabolism global reconstruction (recon 2.1) Recon 2.1. This model is described in the article: Striking a balance with Recon 2.1 Kieran Smallbone Molecular Networks (q-bio.MN) Abstract: Recon 2 is a highly curated reconstruction of the human metabolic network. Whilst the network is state of the art, it has shortcomings, including the presence of unbalanced reactions involving generic metabolites. By replacing these generic molecules with each of their specific instances, we can ensure full elemental balancing, in turn allowing constraint-based analyses to be performed. The resultant model, called Recon 2.1, is an order of magnitude larger than the original. This model is hosted on BioModels Database and identified by: MODEL1311110000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Kieran Smallbone

PROVIDER: MODEL1311110000 | BioModels | 2005-01-01

REPOSITORIES: BioModels

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Publications

Metabolism of vitamin D3 by cytochromes P450.

Sakaki Toshiyuki T Kagawa Norio N Yamamoto Keiko K Inouye Kuniyo K

Frontiers in bioscience : a journal and virtual library 20050101

The vitamin D3 25-hydroxylase (CYP27A1), 25-hydroxyvitamin D3 1alpha-hydroxylase (CYP27B1) and 1alpha,25-dihydroxyvitamin D3 24-hydroxylase (CYP24A1) are members of the cytochrome P450 superfamily, and key enzymes of vitamin D3 metabolism. Using the heterologous expression in E. coli, enzymatic properties of the P450s were recently investigated in detail. Upon analyses of the metabolites of vitamin D3 by the reconstituted system, CYP27A1 surprisingly produced at least seven forms of minor metabo ...[more]

PMID: 15574355

Publication: 1/2787

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Project description:Thiele2013 - Human metabolism global reconstruction (Recon 2) Community-driven global reconstruction of human metabolism (version 2.02). This model is described in the article: A community-driven global reconstruction of human metabolism. Thiele I, et al. Nature Biotechnology Abstract: Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including ~2x more reactions and ~1.7x more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/. This model is hosted on BioModels Database and identified by: MODEL1109130000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Ras plays roles across the spectrum of proliferation, invasion and metastasis. The activity of Ras genes, usually K-Ras, is altered by mutations in around 20% of human cancers, and activation of the Ras-ERK pathway is a critical event in melanomas, colorectal and renal cancers but the degree to which Ras- or Raf-driven transformation is dependent on the activity of the SRF network remains largely obscure. Oncogenic active Ras is known to mediate the cellular response to multiple growth factors leading to the activation of immediate-early genes (IE). A key player in IE gene response is the SRF transcriptional network that we identified being crucial to mediate allegedly the entire transcriptional response downstream of Ras/ERK. The Serum response factor (SRF) is a transcription factor with low intrinsic transcriptional activity and requires the recruitment of one of two families of co-activators: the MRTFs (myocardin-related transcription factors) and the TCFs (ternary complex factors, Elk-1, SAP-1, Net). In particular the TCF, member of the wide family of ETS transcription factors, are specifically activated by MAPK signalling downstream of Ras. We characterised the transcriptional program downstream of Ras/ERK signalling using short TPA stimulations (12-O-tetradecanoyl phorbol-13-acetate, compunt known to induced Ras/ERK activation) by RNA-seq. The investigation of the transcriptional response was performed using Mouse Embryonic Fibroblasts (MEFs) derived from different animals: (i) wild type, (ii) TKO (MEFs derived from mice lacking all three TCFs), (iiI) TKO recon pMY Empty (TKO reconstituted with empty vectors by retrovirus infection), (iv) TKO recon Elk-1 wt (TKO reconstituted with retrovirus vectors expressing Elk-1 wild type by retrovirus infection), (v) TKO recon Elk-1 FW (TKO reconstituted with retrovirus vectors expressing Elk-1 mutant lacking the FW residues in its activation domain), (vi) TKO recon Elk-1 nonA (TKO reconstituted with retrovirus vectors expressing Elk-1 mutant where all phosphor-acceptor residues in its activation domain have been mutagenized to alanines). In order to map SRF and Elk-1 binding sites we performed ChIP-seq of SRF in wild type MEFs and TKO and ChIP-seq of Elk-1 in TKO reconstituted cell lines.

Dataset Information

Smallbone2013 - Human metabolism global reconstruction (recon 2.1)

Publications

Metabolism of vitamin D3 by cytochromes P450.

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