The cooperation of the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, operating in parallel in plants to generate isoprenoid precursors, has been studied extensively. Elucidation of the isoprenoid metabolic pathways is indispensable for the rational design of plant and microbial systems for the production of industrially valuable terpenoids. Here, we describe a new method, based on numerical modeling of mass spectra of metabolically labeled dolichols (Dols), designed to quantitatively follow the cooperation of MVA and MEP reprogrammed upon osmotic stress (sorbitol treatment) in Arabidopsis (). The contribution of the MEP pathway increased significantly (reaching 100%) exclusively for the dominating Dols, while for long-chain Dols, the relative input of the MEP and MVA pathways remained unchanged, suggesting divergent sites of synthesis for dominating and long-chain Dols. The analysis of numerically modeled Dol mass spectra is a novel method to follow modulation of the concomitant activity of isoprenoid-generating pathways in plant cells; additionally, it suggests an exchange of isoprenoid intermediates between plastids and peroxisomes.
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http://dx.doi.org/10.1104/pp.17.00036 | DOI Listing |
Nat Comput Sci
January 2025
AI for Science (AI4S)-Preferred Program, Peking University Shenzhen Graduate School, Shenzhen, China.
Electronic circular dichroism (ECD) spectra contain key information about molecular chirality by discriminating the absolute configurations of chiral molecules, which is crucial in asymmetric organic synthesis and the drug industry. However, existing predictive approaches lack the consideration of ECD spectra owing to the data scarcity and the limited interpretability to achieve trustworthy prediction. Here we establish a large-scale dataset for chiral molecular ECD spectra and propose ECDFormer for accurate and interpretable ECD spectrum prediction.
View Article and Find Full Text PDFJ Proteome Res
January 2025
Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States.
Proteo-SAFARI is a shiny application for fragment assignment by relative isotopes, an R-based software application designed for identification of protein fragment ions directly in the / domain. This program provides an open-source, user-friendly application for identification of fragment ions from a candidate protein sequence with support for custom covalent modifications and various visualizations of identified fragments. Additionally, Proteo-SAFARI includes a nonnegative least-squares fitting approach to determine the contributions of various hydrogen shifted fragment ions ( + 1, + 1, - 1, - 2) observed in UVPD mass spectra which exhibit overlapping isotopic distributions.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Emory University School of Medicine, Atlanta, GA, USA.
Background: The microtubule-associated Tau gene (MAPT) undergoes alternative splicing to produce isoforms with varying combinations of microtubule-binding region (MTBR) repeats (3R, 4R). The MTBR is the predominant region that forms paired helical filaments and neurofibrillary tangles fibrils in disease. Alzheimer's disease (AD) is a mixed Tauopathy containing both 3R and 4R isoforms.
View Article and Find Full Text PDFBackground: Bile acids (BA) are steroids regulating nutrient absorption, energy metabolism, and mitochondrial function, and serve as important signaling molecules with a role in the gut-brain axis. The composition of BAs in humans changes with diet type and health status, which is well documented with a few known bile acids. In this study, we leveraged a new BA-specific spectral library curated in the Dorrestein lab at UCSD to expand the pool of detected BAs in Alzheimer-related LC-MS/MS datasets and provide links to dietary profiles and AD markers.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi-ku, Tokyo, Japan.
Background: Although amyloid deposition in brain is one of the hallmark pathological features of Alzheimer's disease (AD), the upstream events and its molecular environment in AD brain remain largely unknown. Recent advances in analytical methods such as mass spectrometry can provide the cutting-edge tools to unveil the AD pathogenesis at molecular and atomic level.
Method: In order to gain the comprehensive information about AD pathology at molecular level, postmortem brain sections of AD patients were analyzed by the hybrid molecular imaging methods composed of the conventional histological analyses, matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) for small molecules, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging for metals, and particle induced X-ray emission (PIXE) imaging for elements.
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