Article
Chemistry, Multidisciplinary
Asuka Shirakawa, Yoshiyuki Manabe, Roberta Marchetti, Kumpei Yano, Seiji Masui, Alba Silipo, Antonio Molinaro, Koichi Fukase
Summary: The fully sialylated tetraantennary N-glycan was synthesized for the first time using a specific strategy, and the synthesized compounds were used to study the recognition mechanism of neuraminidase.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Maria S. Ledovskaya, Mikhail V. Polynski, Valentine P. Ananikov
Summary: This study proposed two novel synthetic paths for the construction of 3,6-disubstituted pyridazines using acetylene surrogates. By utilizing different reaction modes and substituting reactants, a range of highly deuterated pyridazines were synthesized, while quantum chemical modeling was used to investigate substituent effects in both synthetic pathways.
CHEMISTRY-AN ASIAN JOURNAL
(2021)
Article
Chemistry, Physical
Connor S. MacNeil, Hongyu Zhong, Tyler P. Pabst, Michael Shevlin, Paul J. Chirik
Summary: The cobalt-catalyzed asymmetric hydrogenation of dehydro-sitagliptin was studied and applied to the synthesis of sitagliptin. The discovery of catalysts was accelerated by the synthesis of cationic bis(phosphine) cobalt eta 6-arene complexes. The optimal catalyst showed high yield and enantioselectivity, and maintained excellent activity and selectivity after standing in air for 2 weeks.
Review
Chemistry, Multidisciplinary
Tetsuro Shinada, Atsushi Nakayama, Hironori Okamura, Yoko Yasuno
Summary: Deuterium-labeled organic compounds are essential research tools in scientific research. This review focuses on the synthesis of deuterated aldehydes (RCDO), where the hydrogen at the formyl group is replaced with deuterium. Aldehydes serve as useful starting materials for organic synthesis, allowing for various transformations and derivatizations. Therefore, RCDOs are expected to be powerful starting materials for the synthesis of deuterium-labeled compounds. This review discusses both classical and advanced methods for RCDO synthesis.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2022)
Article
Chemistry, Organic
Carl Recsei, Robert A. Russell, Marina Cagnes, Tamim Darwish
Summary: Uniformly deuterated sterols and related materials are crucial for various studies such as neutron, NMR, tracing, and bioanalysis, as well as for improving lipid nanoparticle formulations. This research focuses on producing sufficient amounts of these materials, including uniformly deuterated squalene and cholesterol with controlled deuteration levels. Additionally, new deuterated sterols (22,23-dihydrobrassicasterol and 24-methylenecholesterol) were prepared, increasing the number of characterized sterols with uniform deuteration. The report also introduces a protocol for separating sterols with different degrees of unsaturation using silylation/silver ion chromatography.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
William T. Heller
Summary: SANS is a powerful tool for studying biological and model lipid membranes, enabling details to be revealed. This article provides an overview of its application for studying lipid bilayer vesicles, the advantages of selective deuteration and contrast variation methods, and approaches to modeling SANS data.
Article
Biochemistry & Molecular Biology
Yoshimichi Sakakibara, Kota Osada, Yasumitsu Uraki, Makoto Ubukata, Kengo Shigetomi
Summary: Hinokitiol, a compound with broad antibacterial activity, was labeled with deuterium as a traceable molecular probe for studying its dynamics in natural environments. Deuteration mainly occurred on the ring and aliphatic hydrogens, providing insights into the biodegradation pathway of hinokitiol. The experimental results suggested that deuteration on the tropolone ring was mediated by D+ while deuteration on the aliphatic group was catalyzed by Pd(II) species.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2021)
Article
Nutrition & Dietetics
Katrin A. Boeckmann, Wolfgang Bernhard, Michaela Minarski, Anna Shunova, Cornelia Wiechers, Christian F. Poets, Axel R. Franz
Summary: This study compared the effects of different deuterated choline components on the kinetics of D9-choline, D9-betaine, and D9-PC. The results showed that D9-choline chloride, D9-GPC, and D9-phosphoryl-choline had similar effects in increasing plasma D9-choline and D9-betaine levels, while D9-POPC shifted the metabolism towards D9-PC. Combined supplementation of GPC and (PO) PC may be the best approach to optimize choline supply in preterm infants.
EUROPEAN JOURNAL OF NUTRITION
(2023)
Article
Engineering, Environmental
Elliott P. Barnhart, Leslie F. Ruppert, Randy Hiebert, Heidi J. Smith, Hannah D. Schweitzer, Arthur C. Clark, Edwin P. Weeks, William H. Orem, Matthew S. Varonka, George Platt, Jenna L. Shelton, Katherine J. Davis, Robert J. Hyatt, Jennifer C. McIntosh, Kilian Ashley, Shuhei Ono, Anna M. Martini, Keith C. Hackley, Robin Gerlach, Lee Spangler, Adrienne J. Phillips, Mark Barry, Alfred B. Cunningham, Matthew W. Fields
Summary: Research has found that complex carbon-containing nutrients can stimulate methane production in coal beds, which has significant implications for understanding biogenic methane production and the formation of methane from underground carbon.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2022)
Article
Astronomy & Astrophysics
Fanny Vazart, Cecilia Ceccarelli, Nadia Balucani, Dimitrios Skouteris
Summary: This paper investigates the formation pathway of the interstellar complex organic molecule glycolaldehyde and finds that it may be formed in the gas phase for a specific solar-like protostar. The study also highlights the need for specific research on the deuterium fractionation of interstellar complex organic molecules, as it cannot be simply predicted based on the parent species.
ASTROPHYSICAL JOURNAL
(2022)
Article
Chemistry, Physical
Masud Monwar, Carlos Cruz, Jared Barr, Max McDaniel
Summary: The Phillips Cr(VI)/silica catalyst widely used in polyethylene production can be activated by nonolefinic hydrocarbons through a self-alkylation mechanism. Different hydrocarbon reductants lead to the formation of unique catalysts with distinctive ligands, influencing their polymerization activity and product specificity. This discovery opens up opportunities for creating novel varieties of Phillips catalysts.
JOURNAL OF CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Kazuhiro Okamoto, Ryosuke Higuma, Kensuke Muta, Keita Fukumoto, Yuta Tsuchihashi, Yosuke Ashikari, Aiichiro Nagaki
Summary: In this study, H-D exchange of one methylene proton was achieved in various dihalomethanes. Highly unstable carbenoid intermediate generation and its decomposition were successfully controlled under high flow-rate conditions. Monofunctionalization of diiodomethane afforded various building blocks, and diverted functionalization of monodeuterated diiodomethane produced products with isotope labeling and monodeuteration.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Emeline Appert, Agnes Martin-Mingot, Omar Karam, Fabien Zunino, Bastien Michelet, Fodil Bouazza, Sebastien Thibaudeau
Summary: The field of medicinal chemistry is currently experiencing a deuterium rush, and the exchange of aromatic hydrogen isotopes is one of the most researched strategies. However, the use of superacidic conditions has been overlooked. This study shows that using TfOD as the reaction medium enables late-stage polydeuteration of pharmaceuticals with various functional groups, complementing existing procedures.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Oliver R. Gedde, Andreas Bonde, Peter Golbaekdal, Troels Skrydstrup
Summary: An expedient method for the ex-situ generation of difluoroiodomethane (DFIM) and its immediate use in a Pd-catalyzed difluoromethylation reaction is reported. The method involves heating a solution of bromodifluoroacetic acid with sodium iodide in sulfolane to generate near stoichiometric amounts of DFIM, which is then used for the subsequent catalytic coupling step. The method allows for the installation of fluorine-containing C-1 groups onto pharmaceutically relevant molecules and is adaptable for deuterium incorporation by adding D2O to the DFIM-generating chamber.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Review
Spectroscopy
Xiaobo Tian, Hjalmar P. Permentier, Rainer Bischoff
Summary: This article summarizes the advances in liquid chromatography and mass spectrometry in proteome quantification approaches, focusing on the principles, benefits, and limitations of chemical isotope labeling-based methods. It also discusses the potential and limitations of multiplex isotope labeling approaches for data-independent acquisition mode.
MASS SPECTROMETRY REVIEWS
(2023)
Article
Cell Biology
Cara L. Green, Heidi H. Pak, Nicole E. Richardson, Victoria Flores, Deyang Yu, Jay L. Tomasiewicz, Sabrina N. Dumas, Katherine Kredell, Jesse W. Fan, Charlie Kirsh, Krittisak Chaiyakul, Michaela E. Murphy, Reji Babygirija, Gregory A. Barrett-Wilt, Joshua Rabinowitz, Irene M. Ong, Cholsoon Jang, Judith Simcox, Dudley W. Lamming
Summary: Research has found that the improvement of metabolic health through reduced dietary protein strongly depends on sex and strain. While some phenotypes remain consistent across different strains and sexes, there is high variability in adiposity, insulin sensitivity, and circulating hormones.
Article
Immunology
Ayaka Sugiura, Gabriela Andrejeva, Kelsey Voss, Darren R. Heintzman, Xincheng Xu, Matthew Z. Madden, Xiang Ye, Katherine L. Beier, Nowrin U. Chowdhury, Melissa M. Wolf, Arissa C. Young, Dalton L. Greenwood, Allison E. Sewell, Shailesh K. Shahi, Samantha N. Freedman, Alanna M. Cameron, Patrik Foerch, Tim Bourne, Juan C. Garcia-Canaveras, John Karijolich, Dawn C. Newcomb, Ashutosh K. Mangalam, Joshua D. Rabinowitz, Jeffrey C. Rathmell
Summary: Antigenic stimulation promotes T cell metabolic reprogramming. The one-carbon metabolism enzyme MTHFD2 regulates purine synthesis and signaling in activated T cells. MTHFD2 deficiency reduces disease severity in multiple in vivo inflammatory disease models.
Meeting Abstract
Oncology
Diana L. Hanna, Gayle S. Jameson, Drew W. Rasco, Angela Tatiana Alistar, Richard C. Frank, Anthony B. El-Khoueiry, Julia Wiedmeier, Caroline Roberts, Brandon Fell, Sarah Hallberg, Denise Roe, Derek Cridebring, Joshua D. Rabinowitz, Stephen Gately, Daniel D. Von Hoff
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Joyce Xu, Xiaoyang Su, Stephen K. Burley, X. F. Steven Zheng
Summary: SOD1 is a crucial antioxidant enzyme that converts superoxide to hydrogen peroxide and molecular oxygen. It is involved in maintaining cellular redox homeostasis and has been linked to various diseases. Recent studies have also highlighted its role as a regulatory protein in cell signaling and transcription. Notably, SOD1 is localized in the nucleus and plays a vital role in oxidative stress response and growth control, especially in the pathogenesis of ALS and cancer.
Article
Cell Biology
Xuetian Yue, Jianming Wang, Chun-Yuan Chang, Juan Liu, Xue Yang, Fan Zhou, Xia Qiu, Vrushank Bhatt, Jessie Yanxiang Guo, Xiaoyang Su, Lanjing Zhang, Zhaohui Feng, Wenwei Hu
Summary: This study found that overexpression of LIF in breast cancer promotes tumorigenesis by increasing glucose uptake and driving glycolysis. It also identifies LIF and its downstream signaling as potential therapeutic targets for breast cancers with LIF overexpression.
CELL DEATH & DISEASE
(2022)
Correction
Oncology
Aamod S. Dekhne, Khushbu Shah, Gregory S. Ducker, Jade M. Katinas, Jennifer Wong-Roushar, Md. Junayed Nayeen, Arpit Doshi, Changwen Ning, Xun Bao, Josephine Fruhauf, Jenney Liu, Adrianne Wallace-Povirk, Carrie O'Connor, Sijana H. Dzinic, Kathryn White, Juiwanna Kushner, Seongho Kim, Maik Huttemann, Lisa Polin, Joshua D. Rabinowitz, Jing Li, Zhanjun Hou, Charles E. Dann, Aleem Gangjee, Larry H. Matherly
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Caroline R. R. Bartman, Daniel R. R. Weilandt, Yihui Shen, Won Dong Lee, Yujiao Han, Tara TeSlaa, Connor S. R. Jankowski, Laith Samarah, Noel R. R. Park, Victoria da Silva-Diz, Maya Aleksandrova, Yetis Gultekin, Argit Marishta, Lin Wang, Lifeng Yang, Asael Roichman, Vrushank Bhatt, Taijin Lan, Zhixian Hu, Xi Xing, Wenyun Lu, Shawn Davidson, Martin Wuehr, Matthew G. G. Vander Heiden, Daniel Herranz, Jessie Yanxiang Guo, Yibin Kang, Joshua D. D. Rabinowitz
Summary: In this study, the rates of glycolysis and the tricarboxylic acid (TCA) cycle were measured in various mouse tissues and cancer models. The research found that TCA cycle flux was suppressed in solid tumors and increased in lung metastases of breast cancer. Although glycolysis was increased in tumors, it was not enough to compensate for the low TCA flux in terms of ATP production. This suggests that solid tumors generally produce ATP at a slower rate than normal.
Article
Oncology
Pochung Jordan Chou, Md Shahid Sarwar, Lujing Wang, Renyi Wu, Shanyi Li, Rasika R. Hudlikar, Yujue Wang, Xiaoyang Su, Ah-Ng Kong
Summary: SAHA is able to regulate mitochondrial metabolism, DNA methylome reprogramming, and transcriptomic gene expression, thus inhibiting LPS-induced inflammatory responses in lung epithelial cells. SAHA treatment significantly alters the levels of metabolites involved in methionine, glutathione, and nicotinamide metabolism. Additionally, SAHA revokes differential methylation in certain gene promoter regions and abrogates the expression of proinflammatory cytokine genes.
CANCER PREVENTION RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Mengqi Hu, Hoang Dinh, Yihui Shen, Patrick F. Suthers, Catherine M. Call, Xuanjia Ye, Jimmy Pratas, Zia Fatma, Huimin Zhao, Joshua D. Rabinowitz, Costas D. Maranas
Summary: The parameterization of kinetic models requires measurement of fluxes and/or metabolite levels for a base strain and genetic perturbations. It remains unclear whether kinetic models constructed for different strains of the same species have similar or significantly different kinetic parameters. In this study, two separate large-scale kinetic models were parameterized using K-FIT for different strains of Saccharomyces cerevisiae, and the results showed strain-specific differences in key metabolic pathways.
METABOLIC ENGINEERING
(2023)
Article
Multidisciplinary Sciences
Won Dong Lee, Lingfan Liang, Jenna AbuSalim, Connor S. R. Jankowski, Laith Z. Samarah, Michael D. Neinast, Joshua D. Rabinowitz
Summary: The method of blood sample collection has significant effects on plasma metabolomics and stable isotope tracing in mice. Stress and sampling site both contribute to differences in the circulating metabolome. Lactate is the most important metabolite in unstressed mice metabolism and is produced in response to acute stress. Noninvasive arterial sampling can avoid these artifacts.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Editorial Material
Endocrinology & Metabolism
Zhaoyue Zhang, Tara TeSlaa, Joshua D. Rabinowitz
Article
Endocrinology & Metabolism
Megan C. Blair, Michael D. Neinast, Cholsoon Jang, Qingwei Chu, Jae Woo Jung, Jessie Axsom, Marc R. Bornstein, Chelsea Thorsheim, Kristina Li, Atsushi Hoshino, Steven Yang, Rachel J. Roth Flach, Bei B. Zhang, Joshua D. Rabinowitz, Zoltan Arany
Summary: Elevated plasma levels of branched-chain amino acids (BCAAs) have been linked to insulin resistance and type 2 diabetes. However, altering BCAA oxidation in skeletal muscle or liver does not improve insulin sensitivity in male mice, despite the effects on plasma BCAA levels. These findings suggest a complex interplay of multiple tissues in the modulation of BCAA metabolism and insulin sensitivity.
Article
Biotechnology & Applied Microbiology
Zong-Yen Wu, Wan Sun, Yihui Shen, Jimmy Pratas, Patrick F. Suthers, Ping-Hung Hsieh, Sudharsan Dwaraknath, Joshua D. Rabinowitz, Costas D. Maranas, Zengyi Shao, Yasuo Yoshikuni
Summary: Through genetic engineering, Issatchenkia orientalis was modified to produce 2.0 g/L of citramalate, showcasing its potential as a promising strain for citramalate production due to its ability to survive at extremely low pH levels.
METABOLIC ENGINEERING COMMUNICATIONS
(2023)
Article
Cell Biology
Kevin R. Zhang, Connor S. R. Jankowski, Rayna Marshall, Rohini Nair, Nestor Mas Gomez, Ahab Alnemri, Yingrui Liu, Elizabeth Erler, Julia Ferrante, Ying Song, Brent A. Bell, Bailey H. Baumann, Jacob Sterling, Brandon Anderson, Sierra Foshe, Jennifer Roof, Hossein Fazelinia, Lynn A. Spruce, Jen-Zen Chuang, Ching-Hwa Sung, Anuradha Dhingra, Kathleen Boesze-Battaglia, Venkata R. M. Chavali, Joshua D. Robinowitz, Claire H. Mitcgell, Joshua L. Dunaief
Summary: Oxidative stress plays a role in age-related macular degeneration, and iron overload can induce oxidative stress in retinal pigment epithelium cells. Iron-loading of induced pluripotent stem cell-derived RPE cells increased lysosomal abundance, impaired proteolysis, and reduced the activity of lysosomal enzymes. In a murine model, iron overload led to lysosomal accumulation, impaired lysosomal function, and cell death in RPE cells.
DISEASE MODELS & MECHANISMS
(2023)
Article
Multidisciplinary Sciences
Brooks Leitner, Won C. Lee, Wanling Zhu, Xinyi D. Zhang, Rafael J. Gaspar, Zongyu Li, Joshua Rabinowitz, Rachel Perry
Summary: Reprogramming metabolism is important for treating sepsis-induced critical illness. This study analyzed the metabolic response of different tissues during sepsis using transcriptomics and metabolomics, revealing tissue-specific mitochondrial reprogramming. The liver showed increased energetic demands and antioxidant synthesis, while skeletal muscle and spleen exhibited unique metabolic signatures. These findings suggest that sepsis leads to tissue-specific metabolic alterations rather than global mitochondrial dysfunction.