Article
Biology
Ikki Sakuma, Hidekazu Nagano, Naoko Hashimoto, Masanori Fujimoto, Akitoshi Nakayama, Takahiro Fuchigami, Yuki Taki, Tatsuma Matsuda, Hiroyuki Akamine, Satomi Kono, Takashi Kono, Masataka Yokoyama, Motoi Nishimura, Koutaro Yokote, Tatsuki Ogasawara, Yoichi Fujii, Seishi Ogawa, Eunyoung Lee, Takashi Miki, Tomoaki Tanaka
Summary: Fructose-1,6-bisphosphatase (FBPase) deficiency, caused by an FBP1 mutation, is a rare disease characterized by hypoglycemic lactic acidosis. This study identified compound heterozygous missense mutations of FBP1 in an adult patient, which resulted in decreased protein expression and loss of enzyme activity. The findings suggest that protein misfolding plays a key role in the pathogenesis of FBPase deficiency, particularly for Type 2 mutations.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiaoyan Liang, Xiaoliang Liu, Wenjing Li, Lu Zhang, Bijun Zhang, Guangrui Lai, Yanyan Zhao
Summary: This article reports a case of rare FBPase deficiency in a Chinese boy, which is caused by mutations in the FBP1 gene. The study found that the mutant FBP1 protein has reduced stability and enzymatic activity, and is subjected to enhanced ubiquitination and proteasomal degradation mediated by NEDD4-2.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Multidisciplinary Sciences
Anna Selezneva, Luke N. M. Harding, Hiten Gutka, Farahnaz Movahedzadeh, Celerino Abad-Zapatero
Summary: This study presents the crystal structures of FBPaseII in both active and inactivated states, providing insights into the catalytic mechanism of this enzyme. The analysis of interatomic distances among the substrate, product, and metal cofactors has led to a revision of the previously proposed mechanism. Furthermore, the study also supports the novel catalytic mechanism of similar enzymes in other microorganisms.
Article
Microbiology
Christina Wilkinson, Meredith T. Morris
Summary: This study demonstrates a complex relationship between FBPase activity and extracellular glucose levels in Trypanosoma brucei, suggesting a potential additional role for FBPase in parasite metabolism. The differential expression of FBPase in various parasite cell lines and growth conditions implies regulation via post-translational modifications. These findings provide new insights into the metabolic pathways of Trypanosoma brucei.
Article
Biochemistry & Molecular Biology
Mandy Pack, Tim Nikolai Gulde, Michelle Victoria Voelcker, Anne S. Boewe, Selina Wrublewsky, Emmanuel Ampofo, Mathias Montenarh, Claudia Goetz
Summary: Glucose homeostasis is vital for organism survival and is regulated by CK2. In this study, a qRT-PCR array was used to identify diabetes-associated genes and it was found that inhibition of CK2 led to decreased gene expression and activity of fructose-1,6-bisphosphatase 1 (FBP1), a central enzyme in gluconeogenesis. As a result, glucose secretion was reduced. These findings highlight FBP1 as a new factor in the CK2-regulated network of carbohydrate metabolism control.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Agriculture, Multidisciplinary
Li Yan-yan, Guo Li-na, Liang Cheng-zhen, Meng Zhi-gang, Syed Tahira, Guo San-dui, Zhang Rui
Summary: Elevated expression levels of cyFBPase and SBPase genes positively regulated each other and had synergistic effects on photosynthesis rates and growth traits of transgenic tobacco plants. Transgenic plants overexpressing cyFBPase and/or SBPase genes showed improvements in sucrose and starch contents.
JOURNAL OF INTEGRATIVE AGRICULTURE
(2022)
Article
Endocrinology & Metabolism
Sara Langer, Rica Waterstradt, Georg Hillebrand, Rene Santer, Simone Baltrusch
Summary: A novel gain-of-function GCK variant was identified in a German family with CHI and obesity, showing increased glucose affinity and enhanced response to activators compared to known variants. Structural analysis highlighted the role of residue 455 in GK activation, providing insights into potential strategies for managing blood glucose levels in CHI and type 2 diabetes.
Article
Radiology, Nuclear Medicine & Medical Imaging
Wanqian Rao, Bei Chen, Ling Xiao, Haoyue Zhu, Chen Chen, Yongxiang Tang, Shuo Hu
Summary: This study found that the expression of fructose-1,6-bisphosphatase 1 (FBP1) is associated with [F-18]FDG PET uptake and postsurgical outcomes in patients with mesial temporal lobe epilepsy (mTLE). The results also showed that FBP1 inhibits [F-18]FDG uptake by regulating GLUT-3 expression. High FBP1 expression is indicative of low GABA(A)R expression and poor prognosis.
EUROPEAN RADIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Beth A. Griesel, Satoshi Matsuzaki, Albert Batushansky, Timothy M. Griffin, Kenneth M. Humphries, Ann Louise Olson
Summary: This study using 3T3-L1 adipocytes as a model system found that an increase in glucose uptake during the first 3 days of differentiation promoted the expansion of the adipocyte metabolome and proteome. The positive effects were specifically due to increased expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), highlighting its critical role in regulating cellular metabolic remodeling for adipocyte differentiation and maturation.
Article
Chemistry, Medicinal
Xiaoyu Wang, Rui Zhao, Wenming Ji, Jie Zhou, Quan Liu, Linxiang Zhao, Zhufang Shen, Shuainan Liu, Bailing Xu
Summary: A series of new indole and benzofuran analogues were designed and synthesized to evaluate their inhibitory activity against FBPase. Compounds with N-acylsulfonamide moiety on the 3-position of the indole-2-carboxylic acid scaffold showed submicromolar IC50 values, providing insights for creating structurally distinct FBPase inhibitors with high potency and drug-like properties. Three X-ray crystal structures of the complexes were solved, revealing the structural basis for the inhibitory activity.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Endocrinology & Metabolism
Magali Gorce, Elise Lebigot, Alina Arion, Anais Brassier, Aline Cano, Pascale De Lonlay, Francois Feillet, Claire Gay, Francois Labarthe, Marie-Cecile Nassogne, Sandrine Roche, Agathe Roubertie, Elise Sacaze, Guy Touati, Pierre Broue
Summary: Fructose-1,6-bisphosphatase deficiency can lead to liver diseases, including hepatomegaly, elevated liver enzymes, and acute liver failure. Liver steatosis may be caused by endoplasmic reticulum stress and de novo lipogenesis activation, potentially resulting in severe long-term liver complications.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Multidisciplinary Sciences
Douglas L. Rothman, Stephen C. Stearns, Robert G. Shulman
Summary: Research indicates that during the Crabtree effect in yeast, short-term adaptation depends on the ability of the glycogen/trehalose shunt to balance the glycolytic pathway, with later gene expression of new isoforms of glycolytic enzymes providing additional homeostatic mechanisms for increased ATP production and product efficiency while maintaining glycolytic balance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Gastroenterology & Hepatology
Guijun Liu, Ningning Wang, Cunzhen Zhang, Min Li, Xuxiao He, Chunzhao Yin, Qiaochu Tu, Xia Shen, Lili Zhang, Jingwen Lv, Yongqiang Wang, Huimin Jiang, Shiting Chen, Nan Li, Yongzhen Tao, Huiyong Yin
Summary: This study reveals the involvement of ALDOB in regulating IR signaling in HCC, with ALDOB loss releasing IR/ALDOB interaction to activate IR signaling pathway, promoting de novo lipogenesis and tumorigenesis. Restoring ALDOB expression or inhibiting AKT phosphorylation shows potential therapeutic strategies in treating HCC.
Article
Biochemistry & Molecular Biology
Isha Sengupta, Payel Mondal, Amrita Sengupta, Atanu Mondal, Vipin Singh, Swagata Adhikari, Sinjini Dhang, Siddhartha Roy, Chandrima Das
Summary: During HBV infection, the upregulation of FBP1 and the reprogramming of Sp110 protein contribute to the progression of HBV-induced HCC. High expression of Sp110 can serve as a prognostic marker and a potential therapeutic target for HBV-induced HCCs.
Article
Genetics & Heredity
Eva Morava, Ulrich A. Schatz, Pernille M. Torring, Mary-Alice Abbott, Matthias Baumann, Charlotte Brasch-Andersen, Nathalie Chevalier, Ulrike Dunkhase-Heinl, Martin Fleger, Tobias B. Haack, Stephen Nelson, Sven Potelle, Silvia Radenkovic, Guido T. Bommer, Emile Van Schaftingen, Maria Veiga-da-Cunha
Summary: Deficiency of PGM2L1 leads to a genetic syndrome with severe developmental and speech delay, dysmorphic facial features, ear anomalies, and other symptoms. The syndrome does not appear to be a glycosylation defect, but suggests an unknown role of glucose-1,6-bisphosphate or other sugar bisphosphates in brain metabolism.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Nutrition & Dietetics
Suzan J. G. Knottnerus, Dewi van Harskamp, Henk Schierbeek, Jeannette C. Bleeker, Loek L. Crefcoeur, Sacha Ferdinandusse, Johannes B. van Goudoever, Riekelt H. Houtkooper, Lodewijk IJlst, Mirjam Langeveld, Ronald J. A. Wanders, Frederic M. Vaz, Frits A. Wijburg, Gepke Visser
Summary: The study investigated the metabolic fates of MCT in healthy individuals using a C-13-labeled MCT tracer. Results showed that when provided as single energy source, 42% of MCT was converted to CO2, while in combination with carbohydrates and proteins in the diet, oxidation of MCT was higher at 62%. Furthermore, less than 1% of C-13-label was incorporated in LCFA in plasma, indicating that administered MCT underwent chain-elongation to LCT.
CLINICAL NUTRITION
(2021)
Article
Genetics & Heredity
Thirsa Conijn, Stephanie C. M. Nijmeijer, Phillis Lakeman, Lidewij Henneman, Frits A. Wijburg, Lotte Haverman
Summary: This study investigated the impact of an educational video compared to an educational text on the knowledge and attitudes toward preconception expanded carrier screening (ECS). Results showed that participants who were offered the video had better genetic knowledge, perceived MPS III as more severe, perceived their risks higher, and were more likely to participate in ECS compared to those who were offered text. Online videos may serve as a valuable tool in genetic counseling, increasing knowledge on ECS and included severe genetic disorders in preconception screening panels.
JOURNAL OF GENETIC COUNSELING
(2021)
Article
Pharmacology & Pharmacy
Arie O. Verkerk, Suzan J. G. Knottnerus, Vincent Portero, Jeannette C. Bleeker, Sacha Ferdinandusse, Kaomei Guan, Lodewijk IJlst, Gepke Visser, Ronald J. A. Wanders, Frits A. Wijburg, Connie R. Bezzina, Isabella Mengarelli, Riekelt H. Houtkooper
Summary: Patients with VLCADD show abnormal levels of long-chain acylcarnitines and electrophysiological abnormalities in hiPSC-CMs, which are not normalized by carnitine supplementation. This suggests that carnitine supplementation may not be beneficial against cardiac arrhythmias in VLCADD patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Andreas Huellen, Kristina Falkenstein, Corina Weigel, Hidde Huidekoper, Nora Naumann-Bartsch, Johannes Spenger, Rene G. Feichtinger, Jacqueline Schaefers, Stephanie Frenz, Daniel Kotlarz, Tooba Momen, Razieh Khoshnevisan, Korbinian M. Riedhammer, Rene Santer, Theresia Herget, Alexander Rennings, Dirk J. Lefeber, Johannes A. Mayr, Christian Thiel, Saskia B. Wortmann
Summary: Fucosylation plays a crucial role in cell functions and is associated with various disorders. This review examines the clinical manifestations, genotypes, and treatment approaches of 25 patients with fucosylation-related defects, as well as discusses the efficacy of fucose therapy.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Pediatrics
Imke Anise Maartje Ditters, Hidde Harmen Huidekoper, Michelle Elisabeth Kruijshaar, Dimitris Rizopoulos, Andreas Hahn, Tiziana Enrico Mongini, Francois Labarthe, Marine Tardieu, Brigitte Chabrol, Anais Brassier, Rossella Parini, Giancarlo Parenti, Nadine Anna Maria Elisabeth van der Beek, Ans Tjitske van der Ploeg, Johanna Maria Pieternel van den Hout
Summary: This study assessed the effect of enzyme replacement therapy (ERT) with alglucosidase alfa on survival and walking ability in patients with classic infantile Pompe disease. The results showed that a high ERT dosage of 40 mg/kg per week significantly improved survival compared to the standard recommended dosage of 20 mg/kg every other week. These findings suggest a need for reconsideration of the currently registered dosage.
LANCET CHILD & ADOLESCENT HEALTH
(2022)
Article
Endocrinology & Metabolism
Marit Schwantje, Merel S. Ebberink, Mirjam Doolaard, Jos P. N. Ruiter, Sabine A. Fuchs, Niklas Darin, Carola Hedberg-Oldfors, Luc Regal, Laura Donker Kaat, Hidde H. Huidekoper, Simon Olpin, Duncan Cole, Stuart J. Moat, Gepke Visser, Sacha Ferdinandusse
Summary: This study describes five patients with thermo-sensitive MTP deficiency, with onset in childhood and myopathic symptoms triggered by fever or exercise. The absence of characteristic acylcarnitine abnormalities poses a risk for delayed diagnosis, while preventive measures can improve symptoms.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Endocrinology & Metabolism
Michiel Bongaerts, Ramon Bonte, Serwet Demirdas, Hidde H. Huidekoper, Janneke Langendonk, Martina Wilke, Walter de Valk, Henk J. Blom, Marcel J. T. Reinders, George J. G. Ruijter
Summary: This study presents a computational approach, called Reafect, that integrates metabolomics data and sequencing data to improve the diagnostic process for finding disease-causing genetic variants in patients with inborn errors of metabolism (IEM). The approach takes into account multiple factors and calculates a score for each reaction in a metabolic pathway. The results show that Reafect accurately identifies deficient enzymes and disease-causing genes, and the integration with CADD scores further improves the prioritization of affected genes. Overall, the findings suggest that metabolomics data enhances the identification of affected genes in IEM patients.
MOLECULAR GENETICS AND METABOLISM
(2022)
Letter
Hematology
Taco W. Kuijpers, Andrica C. H. de Vries, Ester M. van Leeuwen, A. (Ton) A. M. Ermens, Saskia de Pont, Desiree E. C. Smith, Mirjam M. C. Wamelink, Arjen R. Mensenkamp, Marcel R. Nelen, Hana Lango Allen, Steven T. Pals, Berna H. B. Beverloo, Hidde H. Huidekoper, Anja Wagner
Article
Endocrinology & Metabolism
Merel E. Hermans, Michel van Weeghel, Frederic M. Vaz, Sacha Ferdinandusse, Carla E. M. Hollak, Hidde H. Huidekoper, Mirian C. H. Janssen, Andre B. P. van Kuilenburg, Mia L. Pras-Raves, Mirjam M. C. Wamelink, Ronald J. A. Wanders, Mendy M. Welsink-Karssies, Annet M. Bosch
Summary: Classical galactosemia is a common metabolic disorder that leads to intellectual disability and movement disorders. In this study, metabolomics and lipidomics analysis revealed that the disease affects multiple metabolic pathways and compromises the energy status of cells.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Genetics & Heredity
T. Conijn, C. De Roos, H. J. Vreugdenhil, E. M. Van Dijk-Lokkart, F. A. Wijburg, L. Haverman
Summary: This study evaluated the feasibility and effectiveness of time-limited EMDR therapy in reducing PTSD symptoms, psychological comorbidity, distress, and parenting stress in parents of children with a rare progressive life-limiting illness. The results showed that EMDR significantly reduced PTSD symptom severity, as well as comorbid psychological symptoms, distress, and parenting stress. EMDR was well-tolerated, associated with high therapy adherence, and had no adverse events.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Genetics & Heredity
Jordy Dekker, Rachel Schot, Michiel Bongaerts, Walter G. de Valk, Monique M. van Veghel-Plandsoen, Kathryn Monfils, Hannie Douben, Peter Elfferich, Esmee Kasteleijn, Leontine M. A. van Unen, Geert Geeven, Jasper J. Saris, Yvette van Ierland, Frans W. Verheijen, Marianne L. T. van der Sterre, Farah Sadeghi Niaraki, Daphne J. Smits, Hidde H. Huidekoper, Monique Williams, Martina Wilke, Virginie J. M. Verhoeven, Marieke Joosten, Anneke J. A. Kievit, Ingrid M. B. H. van de Laar, Lies H. Hoefsloot, Marianne Hoogeveen-Westerveld, Mark Nellist, Grazia M. S. Mancini, Tjakko J. van Ham
Summary: The study explores the diagnostic potential of RNA-seq in neurodevelopmental disorders (NDDs) and demonstrates its efficacy in molecular diagnosis. RNA-seq analysis on cultured skin fibroblasts helps identify intragenic deletions, monoallelic expression, and variants impacting transcription. The use of cycloheximide treatment and exonic/intronic Z score analysis improves detection and resolution of aberrant splicing. The study highlights the need for customizing RNA-seq and provides a user-friendly web application for diagnostic purposes.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Medical Laboratory Technology
Frederic M. Vaz, Youssra Jamal, Rob Barto, Michael H. Gelb, Andrea E. DeBarber, Ron A. Wevers, Marcel R. Nelen, Aad Verrips, Albert H. Bootsma, Marelle J. Bouva, Nick Kleise, Walter van der Zee, Tao He, Gajja S. Salomons, Hidde H. Huidekoper
Summary: This study aims to test the feasibility of newborn screening for Cerebrotendinous Xanthomatosis (CTX). It was found that using FIA-MS/MS or UPLC-MS/MS to measure the metabolite ratios of three CTX biomarkers is feasible for newborn screening.
CLINICA CHIMICA ACTA
(2023)
Article
Oncology
Imke A. M. Ditters, Harmke A. A. van Kooten, Nadine A. M. E. van der Beek, Jacqueline F. F. Hardon, Gamida Ismailova, Esther Brusse, Michelle E. E. Kruijshaar, Ans T. T. van der Ploeg, Johanna M. P. van den Hout, Hidde H. H. Huidekoper
Summary: This study provides an overview of the experience with home-based infusions of alglucosidase alfa in adult Pompe patients in the Netherlands. The results demonstrate that home administration of alglucosidase alfa is safe and feasible, with the appropriate infrastructure.
Article
Genetics & Heredity
Imke A. M. Ditters, Nadine A. M. E. van der Beek, Esther Brusse, Ans T. van der Ploeg, Johanna M. P. van den Hout, Hidde H. Huidekoper
Summary: Home-based enzyme replacement therapy (ERT) in Pompe disease has been shown to be safe and effective, with few mild symptoms reported during or after infusion. This patient-centered approach to treatment offers increased flexibility and autonomy for patients.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Review
Biochemistry & Molecular Biology
Imke A. M. Ditters, Harmke A. van Kooten, Nadine A. M. E. van der Beek, Ans T. van der Ploeg, Hidde H. Huidekoper, Johanna M. P. van den Hout
Summary: The impact of high antibody titres on treatment response in adults with late-onset Pompe disease remains unclear, but it may contribute to clinical decline in a minority of patients.