Article
Environmental Sciences
Zahid Hassan, Martin Braster, Wilfred F. M. Roling, Hans Westerhoff
Summary: Arsenate-reducing microorganisms can mobilize arsenic into groundwater. A cultivation-based metagenomic strategy was developed to infer actual activities and bridge the knowledge gap between cultivation-independent and cultivation-dependent analyses. This study clarifies the mechanism for arsenic mobilization and redistribution in rural drinking water wells and highlights the potential risks and the need for appropriate bioremediation strategies. Rating: 8/10.
GEOMICROBIOLOGY JOURNAL
(2023)
Article
Biochemical Research Methods
Ian D. Wilson, Colin F. Poole
Summary: Planar chromatography, in the form of thin-layer or high-performance thin-layer chromatography (TLC, HPTLC), remains a powerful and widely used separation technique. It is unparalleled as a simple and rapid qualitative method for mixture analysis, or for identifying bioactive components in mixtures. TLC/HPTLC also allows for the preservation of the separation, enabling further research on components of interest separated in both time and space from the original analysis. The current practice and future developments of planar chromatography are reviewed.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Francesca M. Trovato, Rabiya Zia, Florent Artru, Salma Mujib, Ellen Jerome, Anna Cavazza, Muireann Coen, Ian Wilson, Elaine Holmes, Phillip Morgan, Arjuna Singanayagam, Christine Bernsmeier, Salvatore Napoli, William Bernal, Julia Wendon, Rosa Miquel, Krishna Menon, Vishal C. Patel, John Smith, Stephen R. Atkinson, Evangelos Triantafyllou, Mark J. W. McPhail
Summary: A metabolome study found that ALF patients have dysregulated metabolism and immune responses, potentially mediated by the LPC-ATX-LPA pathway.
JOURNAL OF HEPATOLOGY
(2023)
Article
Chemistry, Organic
Robert N. Goldberg, Robert T. Giessmann, Peter J. Halling, Carsten Kettner, Hans Westerhoff
Summary: The measurement of apparent equilibrium constants K ' for enzyme-catalyzed reactions involves critical details that cannot be neglected in order to avoid systematic errors. Interferences, impurities, and failure to achieve equilibrium are significant factors to consider. Careful reporting of results, including substance identification, reaction specification, reaction conditions, equilibrium constant definition, nomenclature, symbols, units, and uncertainties, is of great importance. This document provides a general discussion on various aspects of equilibrium measurements and STRENDA recommendations regarding the measurements and reporting of results.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemical Research Methods
Allison Brookhart, Mahika Arora, Michael McCullagh, Ian D. Wilson, Robert S. Plumb, Johannes P. C. Vissers, Nikunj Tanna
Summary: Mobile phase selection is crucial in LC-MS studies, affecting various aspects such as retention, selectivity, ionization, and detection limits. This study evaluated the effect of solvent composition on ESI response for 240 small molecular weight drugs. Surface area and surface charge-related features were found to be the main factors influencing ESI response. The composition of the mobile phase had a less significant impact, with some compounds showing a pH effect.
JOURNAL OF CHROMATOGRAPHY A
(2023)
Article
Endocrinology & Metabolism
Yanhua Liu, Hans V. Westerhoff
Summary: Inborn error of metabolism phenylketonuria (PKU) is typically caused by inactivation of phenylalanine hydroxylase (PAH). The reduced PAH activity results in elevated phenylalanine levels and phenylpyruvate in urine. Flux balance analysis (FBA) predicts reduced growth rate in PKU, unless tyrosine is supplemented. However, the PKU phenotype is brain-specific and can be treated by phenylalanine reduction instead of tyrosine supplementation. This study presents an extended FBA model that explains the brain specificity of the disease, the role of phenylpyruvate as a biomarker, the effect of excess phenylalanine on brain pathology, and the superiority of phenylalanine deprivation as therapy.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Biochemical Research Methods
Sarir Sarmad, Mark R. Viant, Warwick B. Dunn, Royston Goodacre, Ian D. Wilson, Katie E. Chappell, Julian L. Griffin, Valerie B. O'Donnell, Brendon Naicker, Matthew R. Lewis, Toru Suzuki
Summary: In this Perspective, the authors propose a four-tiered framework to evaluate the reliability of targeted metabolomics analyses. They discuss the need for community-accepted, harmonized guidelines and summarize the regulatory guidance provided by various authorities. The framework includes levels for discovery, screening, qualification, and validation.
Article
Chemistry, Analytical
Nikunj Tanna, Robert S. Plumb, Billy J. Molloy, Paul D. Rainville, Ian D. Wilson
Summary: The use of vacuum jacketed LC columns (VJC) is evaluated as a potential approach to improve high throughput (HT) analysis. In this study, the VJC method is applied to the bioanalysis of the antidiabetic drug fasiglifam in rat plasma samples. The results show significant improvements in chromatographic performance and separation of the drug from matrix interferences compared to conventional methods. The use of VJC/MS with a rapid 1 min analysis provides a reduction in peak width, higher peak response, and doubled analytical throughput compared to UHPLC/MS method.
Article
Pharmacology & Pharmacy
Billy J. Molloy, Adam King, Lee A. Gethings, Robert S. Plumb, Russell J. Mortishire-Smith, Ian D. Wilson
Summary: The metabolism and pharmacokinetics of fasiglifam, a selective free fatty acid receptor 1 (FFAR1)/GPR40 agonist, were studied in male and female rats. After intravenous administration, peak observed plasma concentrations were seen in both male and female rats. Following oral administration, peak plasma concentrations were obtained for both dose levels in male and female rats. The drug showed low urinary excretion, with a significant sex-related difference. Fasiglifam was the principal drug-related compound in plasma, with 15 metabolites detected.
Article
Mathematics
Hans V. V. Westerhoff
Summary: Dynamic variables in non-equilibrium systems of life are determined by catalytic activities, which are related to genome expression. Modulating gene expression or enzyme function through medicinal drugs is becoming increasingly important. Despite the complexity of cellular systems biology, there are simple principles guiding the control of variables such as fluxes, concentrations, and half-times. By using time-unit invariance, a multitude of laws governing the control coefficients of multiple variables by all catalytic activities can be derived. The control of these variables is determined by time, resulting in simple integer sums when the variables are at maximum, minimum, or steady states.
Article
Biology
David D. van Niekerk, Erik Rust, Frank Bruggeman, Hans V. Westerhoff, Jacky L. Snoep
Summary: By analyzing models from the JWS Online and Biomodels databases, we investigated the use of the disequilibrium ratio as an estimator for the flux control of a reaction. While no functional relationship was found, the disequilibrium ratio can still be used as an estimator for the maximal flux control of a reaction step. We further expanded the analysis by incorporating the overall pathway disequilibrium ratio in the expression, leading to explicit expressions for flux control coefficients.
Article
Biology
Hans V. Westerhoff
Summary: This article resolves the paradoxes between microbial growth rate, enzyme activity, and flux control coefficients. The study found that under optimization conditions, enzyme control coefficients can equal zero, and flux balance analysis effectively maximizes growth yield, thereby resolving these contradictions.
Article
Physics, Multidisciplinary
Yanfei Zhang, Hans V. Westerhoff
Summary: Confronted with unfavorable output processes, free-energy transducers can shift to lower gears to reduce output per unit input. This option is well-known in machines but not appreciated in biology. This study extends thermodynamic principles to explain biological gear shifting and identifies mechanisms. It shows that gear shifting optimizes performance in living systems, allowing them to switch to catabolic pathways with lower ATP stoichiometry, thereby increasing ATP synthesis flux and ensuring continued growth even in challenging conditions.
Review
Chemistry, Medicinal
Lars Weidolf, Ian Wilson
Summary: This article discusses the metabolism and potential toxicities associated with drugs containing carboxylic acid moieties, and explores approaches to mitigate toxicity.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Article
Biology
Frank J. Bruggeman, Maaike Remeijer, Maarten Droste, Luis Salinas, Meike Wortel, Robert Planque, Herbert M. Sauro, Bas Teusink, Hans Westerhoff
Summary: This paper extends the scope of metabolic control analysis (MCA) to a whole-cell context, considering metabolism in the evolutionary context of growth-rate maximisation. The study shows that elementary flux modes (EFMs) naturally emerge as optimal metabolic networks in this context, and their control properties can be derived. The paper also demonstrates the estimation of flux control coefficients from proteomics and ribosome-profiling data. The findings provide insights into the control of metabolic enzymes on growth rate and contribute to the understanding of general principles in cell biochemistry.