Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nazaret2009_TCA_RC_ATP

ABSTRACT: This a model from the article: Mitochondrial energetic metabolism: a simplified model of TCA cycle with ATP production. Nazaret C, Heiske M, Thurley K, Mazat JP J. Theor. Biol. 2009 Jun;258(3):455-64 19007794 , Abstract: Mitochondria play a central role in cellular energetic metabolism. The essential parts of this metabolism are the tricarboxylic acid (TCA) cycle, the respiratory chain and the adenosine triphosphate (ATP) synthesis machinery. Here a simplified model of these three metabolic components with a limited set of differential equations is presented. The existence of a steady state is demonstrated and results of numerical simulations are presented. The relevance of a simple model to represent actual in vivo behavior is discussed.

SUBMITTER: Kieran Smallbone

PROVIDER: BIOMD0000000232 | BioModels | 2009-09-10

REPOSITORIES: BioModels

ACCESS DATA

Json Xml

Publications

Mitochondrial energetic metabolism: a simplified model of TCA cycle with ATP production.

Nazaret Christine C Heiske Margit M Thurley Kevin K Mazat Jean-Pierre JP

Journal of theoretical biology 20081019 3

Mitochondria play a central role in cellular energetic metabolism. The essential parts of this metabolism are the tricarboxylic acid (TCA) cycle, the respiratory chain and the adenosine triphosphate (ATP) synthesis machinery. Here a simplified model of these three metabolic components with a limited set of differential equations is presented. The existence of a steady state is demonstrated and results of numerical simulations are presented. The relevance of a simple model to represent actual in ...[more]

PMID: 19007794

Similar Datasets

A non-canonical tricarboxylic acid cycle underlies cellular identity

Project description:The tricarboxylic acid (TCA) cycle is a central hub of cellular metabolism, oxidizing nutrients to generate reducing equivalents for energy production and critical metabolites for biosynthetic reactions. Despite the importance of the products of the TCA cycle for cell viability and proliferation, mammalian cells display diversity in TCA-cycle activity. How this diversity is achieved, and whether it is critical for establishing cell fate, remains poorly understood. Here we identify a non-canonical TCA cycle that is required for changes in cell state. Genetic co-essentiality mapping revealed a cluster of genes that is sufficient to compose a biochemical alternative to the canonical TCA cycle, wherein mitochondrially derived citrate exported to the cytoplasm is metabolized by ATP citrate lyase, ultimately regenerating mitochondrial oxaloacetate to complete this non-canonical TCA cycle. Manipulating the expression of ATP citrate lyase or the canonical TCA-cycle enzyme aconitase 2 in mouse myoblasts and embryonic stem cells revealed that changes in the configuration of the TCA cycle accompany cell fate transitions. During exit from pluripotency, embryonic stem cells switch from canonical to non-canonical TCA-cycle metabolism. Accordingly, blocking the non-canonical TCA cycle prevents cells from exiting pluripotency. These results establish a context-dependent alternative to the traditional TCA cycle and reveal that appropriate TCA-cycle engagement is required for changes in cell state.

2021-12-01 | GSE183434 | GEO

Metabolically activated energetic materials mediate cell anabolism for bone regeneration

Project description:While cellular energy metabolism regulates tissue regeneration, it remains as a challenge with its limited understanding of activation by engineered scaffolds to regenerate tissue or organ for therapeutic purpose. This study presents a biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [abbreviated as P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), functioning as an endogenous bioenergetic molecule to facilitate bone regeneration and promote cellular anabolism via generations of adenosine triphosphate (ATP) and citrate that enhance the progression of human bone marrow mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our studies demonstrate that 3HB not only significantly enhances in vitro ATP generation to elevate mitochondrial membrane potential (ΔΨm) and capillary-like tube formation, but also increases the content of intermediate metabolite, namely, citrate, in tricarboxylic acid (TCA) cycle, and ultimately promotes the formation of citrate-containing apatite during osteogenesis of hBMSCs. Furthermore, 3HB administration increases the bone mass in rats with ovariectomy (OVX)-induced osteoporosis. Results also show that the P(3HB-co-4HB) scaffold significantly enhances long-term induced bone repair in a rat model with critical-sized calvarial defects, compared to the commercialized available poly-L-lactic acid (PLLA) scaffold. Collectively, these findings uncover a previously undefined role of 3HB in promoting osteogenic differentiation of hBMSCs and highlight that the P(3HB-co-4HB) scaffold functions as a metabolically activated energetic material for bone regeneration.

2023-09-03 | GSE242022 | GEO

Transcription profiling of human Burkittas lymphoma cell line, P493-6 to identify hypoxia responsive genes

Project description:Activation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia. We found that HIF-1 also actively suppresses glucose metabolism through the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA. Forced PDK1 expression in hypoxic HIF-1Î±-null cells increases ATP levels, attenuates hypoxic ROS generation and rescues these cells from hypoxia-induced apoptosis. These studies reveal a novel hypoxia-induced metabolic switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production. Experiment Overall Design: We sought to determine by microarray analysis of gene expression the genes responsive to hypoxia using the human B lymphocyte cell line, P493-6. Hypoxia-responsive genes were globally assessed in cells incubated in 0.1% O2 for 29 hours at which the highest HIF-1 levels were obtained

2008-06-12 | E-GEOD-4086 | biostudies-arrayexpress

Hypoxia responsive genes in human Burkitt’s lymphoma cell line, P493-6.

Project description:Activation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia. We found that HIF-1 also actively suppresses glucose metabolism through the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA. Forced PDK1 expression in hypoxic HIF-1α-null cells increases ATP levels, attenuates hypoxic ROS generation and rescues these cells from hypoxia-induced apoptosis. These studies reveal a novel hypoxia-induced metabolic switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production. Keywords: Hypoxia responsive, case control

2006-03-16 | GSE4086 | GEO

Genes affected by L-arabinose in Salmonella Typhimurium biofilms

Project description:Genes were differentially expressed in wild-type Salmonella Typhimurium biofilms and an ΔaraE mutant when grown in the presence of 5mM or 40mM L-arabinose. Multiple biological pathways were impacted, including genes involved in arabinose metabolism, curli fimbriae, pentose phosphae pathway, TCA cycle. amino acid synthesis, pyrimidine and purine biosynthesis, and ATP synthesis.

2021-03-31 | GSE171196 | GEO

Toll-like receptor signaling rewires macrophage metabolism and promotes histone acetylation via ATP-citrate lyase

Project description:TLR activation induces inflammatory responses in macrophages by activating temporally defined transcriptional cascades within the first hours after stimulation. Whether concurrent changes in the cellular metabolism that occur upon TLR activation influence the quality of the transcriptional responses remain unknown. Here we investigated how macrophages adopt their metabolism early after activation to regulate TLR-inducible gene induction. Macrophages increase glucose metabolism and adopt fluxes through the TCA cycle to foster Citrate synthesis. We concomitantly observe activation of ATP-Citrate Lyase (Acly), resulting in augmented acetyl-CoA synthesis and histone acetylation. To investigate which genes and genes classes require ATP-citrate lyase activity for induction we stimulated bone marrow derived macrophages with LPS after ATP-citrate lyase inhibition.

2019-12-16 | GSE129497 | GEO

MYC sensitises cells to apoptosis by driving energetic demand

Project description:The MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to an imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depleted key TCA cycle metabolites and, in combination with MYC activation, led to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses revealed that glutamine supports viability through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC- driven lymphoma in vivo. In summary, glutamine supports the viability of MYC- overexpressing cells through an energetic rather than a biosynthetic mechanism.

2022-08-11 | PXD034517 | Pride

Integration of the tricarboxylic acid (TCA) cycle with cAMP signaling and Sfl2 pathways in the regulation of CO2 sensing, filamentation, and virulence in Candida albicans

Project description:Candida albicans is the most common opportunistic fungal pathogen of humans and is also a benign member of the gastrointestinal (GI) tract microbiota. Morphological transitions and metabolic regulation are critical for C. albicans to adapt to the changing host environment. We generated a library of central metabolic pathway mutants in the tricarboxylic acid (TCA) cycle, and investigated the functional consequences of these gene deletions on C. albicans biology. Inactivation of the TCA cycle impairs the ability of C. ablicans to utilize non-fermentable carbon sources and dramatically attenuates cell growth rates under several culture conditions. Through integrations with the Ras1-cAMP signaling pathway and the heat shock factor-type transcription regulator Sfl2, we found that the TCA cycle plays fundamental roles in the regulation of CO2 sensing and filamentation. The TCA cycle and cAMP signaling pathways form a regulatory feedback loop, in which ATP and CO2 may function as molecular linkers. We further demonstrate that inactivation of the TCA cycle leads to lowered intracellular ATP and cAMP levels and thus affects the activation of the Ras1-regulated cAMP signaling pathway. In turn, the Ras1-cAMP signaling pathway controls the TCA cycle through both Efg1- and Sfl2-mediated transcriptional regulation in response to elevated CO2 levels. The protein kinase A (PKA) catalytic subunit Tpk1, but not Tpk2, may play a major role in this regulation. Sfl2 specifically binds to several TCA cycle and filamentation-associated genes under high CO2 conditions. Global transcriptional profiling experiments indicate that Sfl2 is indeed required for the gene expression changes occurring in response to these elevated CO2 levels. Finally, we also demonstrate that several key genes of the TCA cycle are essential for virulence and successful colonization of the GI tract in two mouse infection models.

2017-10-04 | GSE102039 | GEO

Elevated Exogenous Pyruvate Potentiates Mesodermal Differentiation through Metabolic Modulation and AMPK/mTOR Pathway in Human Embryonic Stem Cells

Project description:Pyruvate is a key metabolite in glycolysis and tricarboxylic acid (TCA) cycle. Exogenous pyruvate modulates metabolism, provides cellular protection, and is essential for the maintenance of human preimplantation embryos and human embryonic stem cells (hESCs). However, little is known about how pyruvate contributes to cell fate determination during epiblast stage. In this study, we used hESCs as a model to demonstrate that elevated exogenous pyruvate shifts metabolic balance towards oxidative phosphorylation in both maintenance and differentiation conditions. During differentiation, pyruvate potentiates mesoderm and endoderm lineage specification. Pyruvate production and its mitochondrial metabolism are required in BMP4-induced mesoderm differentiation. However, the TCA cycle metabolites do not have the same effect as pyruvate on differentiation. Further study shows that pyruvate increases AMP/ATP ratio, activates AMPK, and then modulates the mTOR pathway to enhance mesoderm differentiation. This study reveals that exogenous pyruvate not only controls metabolism, but also modulates signaling pathways in hESC differentiation.

2019-05-06 | GSE130249 | GEO

Functions of OGDH in primed human embryonic stem cells.

Project description:Human embryonic stem cells (hESCs) can self-renew infinitely, or differentiate into the three germ layer lineages in vitro with certain cues, holding great promise to model early human embryo development ex vivo.It is wildly accepted that hESCs take advantage of both glycolysis and mitochondrial respiration to favor the naïve pluripotency, while prefer glycolysis to support the primed pluripotency. Thus, the function of mitochondrial respiration in primed hESCs has been underestimated for a long time, and has not been fully understood yet. Herein, we report that the adenosine triphosphate (ATP) production rate is comparable between mitochondrial respiration and glycolysis, suggesting that mitoATP serves as one of the major sources of the ATP pool in primed hESCs. Next, we constructed a OGDH knockdown cell line whose ability of mitochondrial respiration was impired. Of note, OGDH deficiency led to the exit of primed pluripotency accompanied by cell death.Collectively, the current study unveils that OGDH acts as a key regulator to fine-tune the abundance of TCA cycle metabolites to ensure the mitochondrial respiration activity in primed hESCs, and highlights the pivotal roles of mitochondrial respiration in terms of ATP production and the maintenance of primed pluripotency.

2022-01-30 | GSE195539 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data