The arogenate dehydratase gene family: Towards understanding differential regulation of carbon flux through phenylalanine into primary versus secondary metabolic pathways

2012 ◽  
Vol 82 ◽  
pp. 22-37 ◽  
Author(s):  
Oliver R.A. Corea ◽  
Diana L. Bedgar ◽  
Laurence B. Davin ◽  
Norman G. Lewis
2018 ◽  
Author(s):  
Mónica Lopes-Marques ◽  
André M. Machado ◽  
Raquel Ruivo ◽  
Elza Fonseca ◽  
Estela Carvalho ◽  
...  

AbstractFatty acids (FAs) constitute a considerable fraction of all lipid molecules with a fundamental role in numerous physiological processes. In animals, the majority of complex lipid molecules are derived from the transformation of FAs through several biochemical pathways. Yet, for FAs to enroll in these pathways they require an activation step. FA activation is catalyzed by the rate limiting action of Acyl-CoA synthases. Several Acyl-CoA enzyme families have been previously described and classified according to the chain length of FA they process. Here, we address the evolutionary history of the ACSBG gene family which activates, FA with more than 16 carbons. Currently, two different ACSBG gene families, ACSBG1 and ACSBG2, are recognized in vertebrates. We provide evidence that a wider and unequal ACSBG gene repertoire is present in vertebrate lineages. We identify a novel ACSBG-like gene lineage which occurs specifically in amphibians, ray finned fish, coelacanths and chondrichthyes named ACSBG3. Also, we show that the ACSBG2 gene lineage duplicated in the Theria ancestor. Our findings, thus offer a far richer understanding on FA activation in vertebrates and provide key insights into the relevance of comparative and functional analysis to perceive physiological differences, namely those related with lipid metabolic pathways.


2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jimmy Zhang ◽  
William R Urciuoli ◽  
Paul S Brookes ◽  
George A Porter ◽  
Sergiy M Nadtochiy

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.


Plants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 128 ◽  
Author(s):  
Haron Salih ◽  
Shoupu He ◽  
Hongge Li ◽  
Zhen Peng ◽  
Xiongming Du

The ethylene-insensitive3-like/ethylene-insensitive3 (EIL/EIN3) protein family can serve as a crucial factor for plant growth and development under diverse environmental conditions. EIL/EIN3 protein is a form of a localized nuclear protein with DNA-binding activity that potentially contributes to the intricate network of primary and secondary metabolic pathways of plants. In light of recent research advances, next-generation sequencing (NGS) and novel bioinformatics tools have provided significant breakthroughs in the study of the EIL/EIN3 protein family in cotton. In turn, this paved the way to identifying and characterizing the EIL/EIN3 protein family. Hence, the high-throughput, rapid, and cost-effective meta sequence analyses have led to a remarkable understanding of protein families in addition to the discovery of novel genes, enzymes, metabolites, and other biomolecules of the higher plants. Therefore, this work highlights the recent advance in the genomic-sequencing analysis of higher plants, which has provided a plethora of function profiles of the EIL/EIN3 protein family. The regulatory role and crosstalk of different metabolic pathways, which are apparently affected by these transcription factor proteins in one way or another, are also discussed. The ethylene hormone plays an important role in the regulation of reactive oxygen species in plants under various environmental stress circumstances. EIL/EIN3 proteins are the key ethylene-signaling regulators and play important roles in promoting cotton fiber developmental stages. However, the function of EIL/EIN3 during initiation and early elongation stages of cotton fiber development has not yet been fully understood. The results provided valuable information on cotton EIL/EIN3 proteins, as well as a new vision into the evolutionary relationships of this gene family in cotton species.


1998 ◽  
Vol 254 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Helene Dominguez ◽  
Catherine Rollin ◽  
Armel Guyonvarch ◽  
Jean-Luc Guerquin-Kern ◽  
Muriel Cocaign-Bousquet ◽  
...  

2018 ◽  
Author(s):  
Kyuho Kang ◽  
Sung Ho Park ◽  
Keunsoo Kang ◽  
Lionel B. Ivashkiv

AbstractComplete polarization of macrophages towards an M1-like proinflammatory and antimicrobial state requires combined action of IFN-γ and LPS. Synergistic activation of canonical inflammatory NF-κB target genes by IFN-γ and LPS is well appreciated, but less is known about whether IFN-γ negatively regulates components of the LPS response, and how this affects polarization. A combined transcriptomic and epigenomic approach revealed that IFN-γ selectively abrogates LPS-induced feedback and select metabolic pathways by suppressing TLR4-mediated activation of gene enhancers. In contrast to superinduction of inflammatory genes via enhancers that harbor IRF sequences and bind STAT1, IFN-γ-mediated repression targeted enhancers with STAT sequences that bound STAT3. TLR4-activated IFN-γ-suppressed enhancers comprised two subsets distinguished by differential regulation of histone acetylation and recruitment of STAT3, CDK8 and cohesin, and were functionally inactivated by IFN-γ. These findings reveal that IFN-γ suppresses feedback inhibitory and metabolic components of the TLR response to achieve full M1 polarization, and provide insights into mechanisms by which IFN-γ selectively inhibits TLR4-induced transcription.


2021 ◽  
Vol 8 (6) ◽  
pp. 106-107
Author(s):  
Kira L. Tomlinson ◽  
Sebastián A. Riquelme

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.


2020 ◽  
Author(s):  
Anna A. Hippmann ◽  
Nina Schuback ◽  
Kyung-Mee Moon ◽  
John P. McCrow ◽  
Andrew E. Allen ◽  
...  

AbstractDiatoms are one of the most successful phytoplankton groups in our oceans, being responsible for over 20% of the Earth’s photosynthetic productivity. Their chimeric genomes have genes derived from red algae, green algae, bacteria and heterotrophs, resulting in multiple isoenzymes targeted to different cellular compartments with the potential for differential regulation under nutrient limitation. The resulting interactions between metabolic pathways are not yet fully understood.We previously showed how acclimation to Cu limitation enhanced susceptibility to overreduction of the photosynthetic electron transport chain and its reorganization to favor photoprotection over light-harvesting in the oceanic diatom Thalassiosira oceanica (Hippmann et al., 2017). In order to understand the overall metabolic changes that help alleviate the stress of Cu limitation, we generated comprehensive proteomic datasets from the diatom Thalassiosira oceanica grown under Cu-limiting and -replete conditions. The datasets were used to identify differentially expressed proteins involved in carbon, nitrogen and oxidative stress-related metabolic pathways and to predict the proteins cellular location.Metabolic pathway analysis showed integrated responses to Cu limitation in diatoms. The up-regulation of ferredoxin (Fdx) was correlated with up-regulation of plastidial Fdx-dependent isoenzymes involved in nitrogen assimilation as well as enzymes involved in glutathione synthesis thus integrating nitrogen uptake and metabolism with photosynthesis and oxidative stress resistance. The differential regulation of glycolytic isoenzymes located in the chloroplast and mitochondria enables them to channel both excess electrons and/or ATP between these compartments. Additional evidence for chloroplast-mitochondrial cross-talk is shown by up-regulation of chloroplast and mitochondrial proteins involved in the proposed malate shunt.One sentence summaryDiatoms adapt to Cu limitation by regulating their large repertoire of isoenzymes to channel electrons away from the chloroplast, enhance nitrogen uptake, and integrate the oxidative stress response. 123


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