| 1. |
- Hofer, Gerhard, et al.
(författare)
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Metal Ion Promiscuity and Structure of 2,3-Dihydroxybenzoic Acid Decarboxylase of Aspergillus oryzae
- 2021
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 22:4, s. 652-656
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Tidskriftsartikel (refereegranskat)abstract
- Broad substrate tolerance and excellent regioselectivity, as well as independence from sensitive cofactors have established benzoic acid decarboxylases from microbial sources as efficient biocatalysts. Robustness under process conditions makes them particularly attractive for preparative-scale applications. The divalent metal-dependent enzymes are capable of catalyzing the reversible non-oxidative (de)carboxylation of a variety of electron-rich (hetero)aromatic substrates analogously to the chemical Kolbe-Schmitt reaction. Elemental mass spectrometry supported by crystal structure elucidation and quantum chemical calculations verified the presence of a catalytically relevant Mg2+ complexed in the active site of 2,3-dihydroxybenoic acid decarboxylase from Aspergillus oryzae (2,3-DHBD_Ao). This unique example with respect to the nature of the metal is in contrast to mechanistically related decarboxylases, which generally have Zn2+ or Mn2+ as the catalytically active metal.
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| 2. |
- Lozano, Manuel, et al.
(författare)
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Prenatal Metals Exposure and pre-adolescents’ Emotional and Behavioral Problems
- 2024
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Ingår i: Exposure and Health. - 2451-9766. ; 16:3, s. 679-692
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Tidskriftsartikel (refereegranskat)abstract
- Emotional and behavioral problems during childhood raise the risk of subsequent developmental of mental disorders. Our aim was to study the association between maternal metal and trace element concentrations during gestation and these problems in 9 year-old children. The study sample comprised Spanish mother-child pairs in the INMA project (n = 1003). Metals and trace elements (As, Cd, Co, Cu, Mo, Ni, Pb, Sb, Se, Tl and Zn) were measured in urine samples collected during pregnancy. Inorganic As metabolites were speciated in a subsample (n = 729). Emotional and behavioral problems were assessed using the Child Behavior Checklist (CBCL) composed of three scales: internalizing, externalizing and total problems. Sociodemographic, dietary and exposure to other environmental pollutants were obtained through questionnaires. Single nucleotide polymorphisms in brain- and metabolism-related genes APOE, BDNF, GSTP1, and PON1 were determined in cord blood. Multivariate negative binomial models were used. The interaction with sex and genotypes was evaluated including interaction terms. A multi-element analysis was carried out by a principal component analysis. Higher concentrations of Cu, monomethylarsonic acid, and Pb during pregnancy were associated with an increased incidence ratio risk (IRR) between 4.6 and 7.5% for internalizing and externalizing problems for all three CBCL scales in the children. Increasing Mo, Ni and Co concentrations were associated with higher IRR for internalizing problems (up to 8%), and Cd for externalizing problems (6.7%). Modifications by sex and genotypes were found for several associations. Multi-element analysis associated multiple metals and trace elements (Ni, Cu, Se, Cd and Pb) with higher internalizing problems.
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| 3. |
- Mayer, Florian, et al.
(författare)
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Best of Both Worlds: Adsorptive Ultrafiltration Nanocellulose-Hypercrosslinked Polymer Hybrid Membranes for Metal Ion Removal
- 2024
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Ingår i: Small Science. - : John Wiley & Sons. - 2688-4046.
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Tidskriftsartikel (refereegranskat)abstract
- Efficient water treatment ideally combines ion exchange for the removal of hardness elements and toxic trace metals as well as ultrafiltration for the removal of particulate matter. Although promising for adsorption, many high-surface-area polymer materials cannot be easily processed into freestanding membranes or packed bed columns, due to poor solution processability and high back pressures, respectively. The preparation of hybrid membranes comprising sulfonated hypercrosslinked polymers entrapped in nanocellulose papers is described. The hybrid membranes are effective for simultaneous ultrafiltration and ion exchange. Increasing the polymer loading of the hybrid membrane produces synergy by increasing the permeance of the membranes while enhancing the ion adsorption capacity to values exceeding those of bulk hypercrosslinked polymers. The maximum ion adsorption capacity for copper is determined to be ≈100 mg g−1 outperforming that of pure polymer (71 mg g−1) and commercially available ion exchange resins. Competitive adsorption is tested in samples containing water hardness elements and trace toxic metal ions showing high ion-exchange capacities. Even when fully loaded with water hardness elements, Ba2+ and Sr2+ are still removed from solution.
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| 4. |
- Sheng, Xiang, et al.
(författare)
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Reaction Mechanism and Substrate Specificity of Iso-orotate Decarboxylase : A Combined Theoretical and Experimental Study
- 2018
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Ingår i: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The C-C bond cleavage catalyzed by metal-dependent iso-orotate decarboxylase (IDCase) from the thymidine salvage pathway is of interest for the elucidation of a (hypothetical) DNA demethylation pathway. IDCase appears also as a promising candidate for the synthetic regioselective carboxylation of N-heteroaromatics. Herein, we report a joint experimental-theoretical study to gain insights into the metal identity, reaction mechanism, and substrate specificity of IDCase. In contrast to previous assumptions, the enzyme is demonstrated by ICPMS/MS measurements to contain a catalytically relevant Mn(2+)rather than Zn2+. Quantum chemical calculations revealed that decarboxylation of the natural substrate (5-carboxyuracil) proceeds via a (reverse) electrophilic aromatic substitution with formation of CO2. The occurrence of previously proposed tetrahedral carboxylate intermediates with concomitant formation of HCO3- could be ruled out on the basis of prohibitively high energy barriers. In contrast to related o-benzoic acid decarboxylases, such as y-resorcylate decarboxylase and 5-carboxyvanillate decarboxylase, which exhibit a relaxed substrate tolerance for phenolic acids, IDCase shows high substrate fidelity. Structural and energy comparisons suggest that this is caused by a unique hydrogen bonding of the heterocyclic natural substrate (5-carboxyuracil) to the surrounding residues. Analysis of calculated energies also shows that the reverse carboxylation of uracil is impeded by a strongly disfavored uphill reaction.
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| 5. |
- Soler-Blasco, Raquel, et al.
(författare)
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Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children.
- 2023
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Ingår i: Environmental science & technology. - 1520-5851. ; 57:41, s. 15366-15378
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Tidskriftsartikel (refereegranskat)abstract
- We explored the influence of child and maternal single nucleotide polymorphisms (SNPs) in genes related to neurological function and arsenic metabolism (i.e., ABCA1, ABCB1, PON1, CYP3A, BDNF, GSTP1, MT2A, and APOE as well as AS3MT) on the association between prenatal arsenic (As) exposure and methylation efficiency and neuropsychological development in 4-5-year-old children. Participants were 549 mother-child pairs from the INMA (Environment and Childhood) Spanish Project. We measured inorganic arsenic (iAs) and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in urine samples collected during pregnancy. Neuropsychological development was assessed at the age of 4-5 years using the McCarthy Scales of Children's Abilities (MSCA). Several SNPs were determined in maternal and child DNA; AS3MT and APOE haplotypes were inferred. The median ∑As (sum of iAs, DMA, and MMA) was 7.08 μg/g creatinine. Statistically significant interactions for children's APOE haplotype were observed. Specifically, ε4-carrier children had consistently lower MSCA scores in several scales with increasing ∑As and MMA concentrations. These results provide evidence regarding the neurotoxic effects of early life exposure to As, observing that the APOE ε4 allele could make children more vulnerable to this exposure.
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