| 1. |
- Cederfelt, Daniela, et al.
(författare)
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The Allosteric Regulation of Β-Ureidopropionase Depends on Fine-Tuned Stability of Active-Site Loops and Subunit Interfaces
- 2023
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- The activity of β-ureidopropionase, which catalyses the last step in the degradation of uracil, thymine, and analogous antimetabolites, is cooperatively regulated by the substrate and product of the reaction. This involves shifts in the equilibrium of the oligomeric states of the enzyme, but how these are achieved and result in changes in enzyme catalytic competence has yet to be determined. Here, the regulation of human β-ureidopropionase was further explored via site-directed mutagenesis, inhibition studies, and cryo-electron microscopy. The active-site residue E207, as well as H173 and H307 located at the dimer-dimer interface, are shown to play crucial roles in enzyme activation. Dimer association to larger assemblies requires closure of active-site loops, which positions the catalytically crucial E207 stably in the active site. H173 and H307 likely respond to ligand-induced changes in their environment with changes in their protonation states, which fine-tunes the active-site loop stability and the strength of dimer-dimer interfaces and explains the previously observed pH influence on the oligomer equilibrium. The correlation between substrate analogue structure and effect on enzyme assembly suggests that the ability to favourably interact with F205 may distinguish activators from inhibitors. The cryo-EM structure of human β-ureidopropionase assembly obtained at low pH provides first insights into the architecture of its activated state. and validates our current model of the allosteric regulation mechanism. Closed entrance loop conformations and dimer-dimer interfaces are highly conserved between human and fruit fly enzymes.
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| 2. |
- Geng, Dawei, 1986-, et al.
(författare)
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Effect of perfluorooctanesulfonic acid (PFOS) on the liver lipid metabolism of the developing chicken embryo
- 2019
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Ingår i: Ecotoxicology and Environmental Safety. - : Elsevier. - 0147-6513 .- 1090-2414. ; 170, s. 691-698
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Tidskriftsartikel (refereegranskat)abstract
- Perfluorooctanesulfonate (PFOS) is a well-known contaminant in the environment and it has shown to disrupt multiple biological pathways, particularly those related with lipid metabolism. In this study, we have studied the impact of in ovo exposure to PFOS on lipid metabolism in livers in developing chicken embryos using lipidomics for detailed characterization of the liver lipidome. We used an avian model (Gallus gallus domesticus) for in ovo treatment at two levels of PFOS. The lipid profile of the liver of the embryo was investigated by ultra-high performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry and by gas chromatography mass spectrometry. Over 170 lipids were identified, covering phospholipids, ceramides, di- and triacylglycerols, cholesterol esters and fatty acid composition of the lipids. The PFOS exposure caused dose dependent changes in the lipid levels, which included upregulation of specific phospholipids associated with the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, triacylglycerols with low carbon number and double bond count as well as of lipotoxic ceramides and diacylglycerols. Our data suggest that at lower levels of exposure, mitochondrial fatty acid β-oxidation is suppressed while the peroxisomal fatty acid β -oxidation is increased. At higher doses, however, both β -oxidation pathways are upregulated.
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| 3. |
- Thanh, Wang, et al.
(författare)
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Literature survey on the environmental contamination of liquid crystal monomers (LCMs) and a pilot study on their occurrence in sewage sludge from Sweden
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Liquid crystal displays (LCDs) are currently the predominant display technology in the market and utilized in various devices from small calculators to large flat-screen TVs. Liquid crystal monomers (LCMs) are essential components of LCDs and have been produced at a large scale since the 1980s. Concerns have arisen about the potential environmental release of LCMs, with recent studies detecting their presence in indoor dust, sediments, soils and even in humans. The large number of LCMs and their structural diversity poses challenges in chemical analysis. Furthermore, there are discrepancies in acronyms between different studies, which emphasize the need for a standardized nomenclature for reporting LCMs. Experimental data on physical-chemical properties, atmospheric lifetimes, and bioaccumulation potential highlight the potential persistent organic pollutant characteristics of many LCMs. LCMs can be released to the environment during manufacturing, product use, and recycling processes. Environmental monitoring of LCMs is in its early stages, with limited data available. Studies have reported LCM presence in indoor dust, outdoor environments, soil, sediment and biota, primarily from China. Human exposure has been suggested through occupational settings and there have been positive correlations between LCM levels in indoor dust and human breast milk. However, more studies are needed from other countries to assess whether LCMs have widespread global contamination. Within this current report, a pilot study was conducted with the aim to investigate occurrence of selected LCMs in sewage sludge. However, challenges during analytical method development with the sample extraction and pretreatment steps led to low recoveries of native LCMs, indicating the need for further method optimization. A clear conclusion can therefore not be made whether LCMs are present or not in Swedish sludge.
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