The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Eduard A Struys - One of the best experts on this subject based on the ideXlab platform.

  • deficiency in slc25a1 encoding the mitochondrial citrate carrier causes combined d 2 and l 2 hydroxyglutaric aciduria
    American Journal of Human Genetics, 2013
    Co-Authors: Benjamin Nota, M. Kranendijk, Matilde Fernandez R Ojeda, Silvy J M Van Dooren, Marianna R Bevova, Warsha A Kanhai, Erwin E.w. Jansen, Eduard A Struys, Erik A Sistermans, Aggie W.m. Nieuwint
    Abstract:

    The Krebs cycle is of fundamental importance for the generation of the energetic and molecular needs of both prokaryotic and eukaryotic cells. Both enantiomers of metabolite 2-hydroxyglutarate are directly linked to this pivotal Biochemical Pathway and are found elevated not only in several cancers, but also in different variants of the neurometabolic disease 2-hydroxyglutaric aciduria. Recently we showed that cancer-associated IDH2 germline mutations cause one variant of 2-hydroxyglutaric aciduria. Complementary to these findings, we now report recessive mutations in SLC25A1, the mitochondrial citrate carrier, in 12 out of 12 individuals with combined D-2- and L-2-hydroxyglutaric aciduria. Impaired mitochondrial citrate efflux, demonstrated by stable isotope labeling experiments and the absence of SLC25A1 in fibroblasts harboring certain mutations, suggest that SLC25A1 deficiency is pathogenic. Our results identify defects in SLC25A1 as a cause of combined D-2- and L-2-hydroxyglutaric aciduria.

  • d 2 hydroxyglutaric aciduria unravelling the Biochemical Pathway and the genetic defect
    Journal of Inherited Metabolic Disease, 2006
    Co-Authors: Eduard A Struys
    Abstract:

    D-2-Hydroxyglutaric aciduria (D-2-HGA) is a neurometabolic inherited disorder first described in 1980. In the following years, it became clear that the clinical phenotype of the disease varies widely from severe neonatal to asymptomatic. However, the sparse Biochemical knowledge made D-2-HGA a poorly understood disease. Much progress has been made in the last five years in various studies, revealing two human enzymes that play a role in the metabolism of D-2-hydroxyglutarate (D-2-HG): hydroxyacid-oxoacid transhydrogenase (HOT) and D-2-HG dehydrogenase. HOT is expected to be responsible for the formation of D-2-HG, while D-2-HG dehydrogenase converts D-2-HG into 2-ketoglutarate. We demonstrated pathogenic mutations in the D2HGD gene in patients with D-2-HGA, helping to unravel the primary defect causing D-2-HGA. However, in approximately 50% of the patients with D-2-HGA examined, no pathogenic mutations have yet been found.

Weiliang Chao - One of the best experts on this subject based on the ideXlab platform.

  • biodegradation of an endocrine disrupting chemical di n butyl phthalate by newly isolated agrobacterium sp and the Biochemical Pathway
    Process Biochemistry, 2011
    Co-Authors: Yangyang Wang, Renxing Liang, Qinyun Dai, Decai Jin, Weiliang Chao
    Abstract:

    Abstract A bacterial strain capable of utilizing di- n -butyl phthalate (DBP) as its sole source of carbon and energy was isolated from river sludge. Based on its 16S rRNA gene sequence, the strain was identified as Agrobacterium sp. This is the first report about DBP degradation by Agrobacterium sp. The results showed that pH 8.0, 30 °C, substrate concentration lower than 200 mg/l were optimal for degradation. The investigation of degradation kinetics at different initial concentrations showed that DBP degradation was exponential. The half-life of degradation was about 10.4 h when the concentration of DBP was lower than 200 mg/l. The degradation rate of DBP was influenced by the presence of dimethyl phthalate (DMP). In batch culture, the degradation intermediates of DBP were identified as mono-butyl phthalate (MBP) and phthalate acid (PA). The Pathway of DBP degradation was DBP to MBP and then to PA before mineralization. Our results provide additional evidence of the wide spectrum of phthalate esters utilization by this strain and suggest the possibility of applying Agrobacterium sp. for remediation of contamination.

Florian Mittag - One of the best experts on this subject based on the ideXlab platform.

  • path2models large scale generation of computational models from Biochemical Pathway maps
    BMC Systems Biology, 2013
    Co-Authors: Finja Buchel, Nicolas Rodriguez, Neil Swainston, Clemens Wrzodek, Tobias Czauderna, Roland Keller, Florian Mittag
    Abstract:

    Background: Systems biology projects and omics technologies have led to a growing number of Biochemical Pathway models and reconstructions. However, the majority of these models are still created de novo, based on literature mining and the manual processing of Pathway data. Results: To increase the efficiency of model creation, the Path2Models project has automatically generated mathematical models from Pathway representations using a suite of freely available software. Data sources include KEGG, BioCarta, MetaCyc and SABIO-RK. Depending on the source data, three types of models are provided: kinetic, logical and constraint-based. Models from over 2 600 organisms are encoded consistently in SBML, and are made freely available through BioModels Database at http://www.ebi.ac.uk/biomodels-main/path2models. Each model contains the list of participants, their interactions, the relevant mathematical constructs, and initial parameter values. Most models are also available as easy-to-understand graphical SBGN maps.

  • large scale generation of computational models from Biochemical Pathway maps
    arXiv: Molecular Networks, 2013
    Co-Authors: Finja Buchel, Nicolas Rodriguez, Neil Swainston, Clemens Wrzodek, Tobias Czauderna, Roland Keller, Florian Mittag, Michael Schubert, Mihai Glont, Martin Golebiewski
    Abstract:

    Background: Systems biology projects and omics technologies have led to a growing number of Biochemical Pathway reconstructions. However, mathematical models are still most often created de novo, based on reading the literature and processing Pathway data manually. Results: To increase the efficiency with which such models can be created, we automatically generated mathematical models from Pathway representations using a suite of freely available software. We produced models that combine data from KEGG Pathway, BioCarta, MetaCyc and SABIO-RK; According to the source data, three types of models are provided: kinetic, logical and constraint-based. All models are encoded using SBML Core and Qual packages, and available through BioModels Database. Each model contains the list of participants, the interactions, and the relevant mathematical constructs, but, in most cases, no meaningful parameter values. Most models are also available as easy to understand graphical SBGN maps. Conclusions: to date, the project has resulted in more than 140000 models freely available. We believe this resource can tremendously accelerate the development of mathematical models by providing initial starting points ready for parametrization.

Yuping Wang - One of the best experts on this subject based on the ideXlab platform.

  • degradation of the endocrine disrupting dimethyl phthalate carboxylic ester by sphingomonas yanoikuyae dos01 isolated from the south china sea and the Biochemical Pathway
    International Biodeterioration & Biodegradation, 2009
    Co-Authors: Boping Han, Shunshan Duan, Zhenye Zhao, Yuping Wang
    Abstract:

    Abstract Bacteria capable of using dimethyl phthalate (DMP) as the sole carbon and energy source were isolated from the sediments collected at a depth of 1340 m from the South China Sea. Sphingomonas yanoikuyae DOS01, identified based on 16S rRNA gene sequence, utilized DMP from an initial level of 180 mg l −1 to non-detectable in 35 h at 30 °C, the optical density (OD 600 ) values increased over the time of incubation. Degradation intermediate monomethyl phthalate (MMP) accumulated up to 21.3 mg l −1 and then disappeared in the culture medium. When MMP or another intermediate phthalate (PA) was used as the sole substrate, this strain was only capable of degrading MMP, but not PA. Total organic carbon (TOC) analysis of the culture medium suggested that both DMP and MMP were mineralized, but not PA. This strain from the deep-ocean sediment transforms DMP to MMP using a common Biochemical Pathway for DMP as reported before. Further esterase activity assays indicated that the enzyme induced by MMP has higher affinity than that by DMP for the substrate p -nitrophenyl acetate. Our results indicated that complete degradation of DMP by this marine microorganism may involve a new Biochemical Pathway.

Laure Poirier - One of the best experts on this subject based on the ideXlab platform.

  • metabolic control within the jasmonate Biochemical Pathway
    Plant and Cell Physiology, 2019
    Co-Authors: Thierry Heitz, Ekaterina A Smirnova, Valentin Marquis, Laure Poirier
    Abstract:

    Regulation of defense and developmental responses by jasmonates (JAs) has been intensively investigated at genetic and transcriptional levels. Plasticity in the jasmonic acid (JA) metabolic Pathway as a means to control signal output has received less attention. Although the amplitude of JA responses generally follows the accumulation dynamics of the active hormone jasmonoyl-isoleucine (JA-Ile), emerging evidence has identified cases where this relationship is distorted and that we discuss in this review. JA-Ile is turned over in Arabidopsis by two inducible, intertwined catabolic Pathways; one is oxidative and mediated by cytochrome P450 enzymes of the subfamily 94 (CYP94), and the other proceeds via deconjugation by amidohydrolases. Their genetic inactivation has profound effects on JAs homeostasis, including strong JA-Ile overaccumulation, but this correlates with enhanced defense and tolerance to microbial or insect attacks only in the absence of overinduction of negative signaling regulators. By contrast, the impairment of JA oxidation in the jasmonic acid oxidase 2 (jao2) mutant turns on constitutive defense responses without elevating JA-Ile levels in naive leaves and enhances resistance to subsequent biotic stress. This latter and other recent cases of JA signaling are associated with JA-Ile catabolites accumulation rather than more abundant hormone, reflecting increased metabolic flux through the Pathway. Therefore, manipulating upstream and downstream JA-Ile homeostatic steps reveals distinct metabolic nodes controlling defense signaling output.