Article
Biochemistry & Molecular Biology
Qiaoyun Chu, Ping Liu, Yihan Song, Ronghui Yang, Jing An, Xuewei Zhai, Jing Niu, Chuanzhen Yang, Binghui Li
Summary: Reprogramming of lipid metabolism is a hallmark of cancer, but the involvement of specific fatty acids and enzymes in tumorigenesis is not well understood. This study shows that depletion of the enzyme acetyl-CoA carboxylase inhibits the synthesis and elongation of very long-chain fatty acids in human cancer cells. Deficiency of very long-chain fatty acids impairs mitochondrial morphology and makes cancer cells susceptible to oxidative stress and cell death.
Article
Immunology
Abbe N. Vallejo, Henry J. Mroczkowski, Joshua J. Michel, Michael Woolford, Harry C. Blair, Patricia Griffin, Elizabeth McCracken, Stephanie J. Mihalik, Miguel Reyes-Mugica, Jerry Vockley
Summary: The study found that patients with VLCADD exhibit systemic inflammatory responses during symptomatic and asymptomatic periods, with an abundance of immune cells expressing high levels of inflammatory mediators. Patients with recurrent hospitalisations showed sustained high levels of plasma cytokines and higher intracellular stores of inflammatory molecules in monocytes.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rasmus Stenlid, Hannes Manell, Rikard Seth, Sara Y. Cerenius, Azazul Chowdhury, Camilla Roa Cortes, Isabelle Nyqvist, Thomas Lundqvist, Maria Halldin, Peter Bergsten
Summary: This study found that patients with VLCAD and MCAD have significantly lower plasma glucagon concentrations compared to patients with CUD, while the concentrations in the CUD group were similar to normative data, suggesting that glucagon secretion may be impaired in patients with VLCAD or MCAD.
Article
Medical Laboratory Technology
Salim Ahmed Al-Busaidi, Jawaher Al Al Nou'mani, Zubaida Al-Falahi, Rajaa Al-Farsi, Suneel Kumar, Fathiya Al-Murshedi, Kathiya Awlad-Thani, Ayda Al Nabhani, Abdullah M. Al Alawi
Summary: A 14-year-old boy diagnosed with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) also developed type 1 diabetes mellitus (DM1). Managing this patient is challenging due to potentially paradoxical life-threatening complications of the two diseases.
CLINICAL BIOCHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Weibo Wang, Qingpeng Wei, Jiayuan Zhang, Meiqi Zhang, Chuchen Wang, Renyu Qu, Yuan Wang, Guangfu Yang, Jing Wang
Summary: This study developed a genetically encoded fluorescent sensor for ratiometric quantification of LCACoAs in living cells, demonstrating conformational changes of LCACoA molecules and real-time monitoring. The research also revealed the impact of disruptions in ACSL enzymes and ACBP genes on the levels and distribution of LCACoAs in cytosol and mitochondria.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Ravi R. Sonani, Artur Blat, Grzegorz Dubin
Summary: This study solved the crystal structures of human ACOX1a, revealing its homodimeric form and the binding of two FAD molecules at the active site. It also found that the substrate binding cleft of ACOX1a is wider compared to other fatty acid oxidation enzymes. Furthermore, the study analyzed the impact of mutations causing dysfunctionality of ACOX1a on its structure and function.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Multidisciplinary Sciences
Yuxun Zhang, Eric Goetzman
Summary: Mitochondrial trifunctional protein (TFP) plays a crucial role in chain-shortening long-chain fatty acids within the mitochondria. Despite being heavily modified by acetyllysine and succinyllysine post-translational modifications, the functional significance of these modifications on TFP remains unclear. Research suggests that TFP in the membrane-bound state may be protected from lysine acylation, which could impact its enzymatic activity.
Article
Agriculture, Multidisciplinary
Wang Ma, Jin Li, Wen-Qian Yang, Zi-Yi Zhang, Chun-Xiao Yan, Peng-Wei Huang, Xiao-Man Sun
Summary: This study investigates the production of odd chain fatty acids (OCFAs) by Schizochytrium sp., a microorganism with potential for efficient OCFA production. Different substrates and genetic modifications were used to enhance propionyl-CoA supply and inhibit its consumption, leading to increased OCFA accumulation. A fed-batch co-feeding strategy further improved OCFA production. The findings provide guidance for microbial production of OCFAs.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Review
Plant Sciences
Huayan Zhao, Dylan K. Kosma, Shiyou Lu
Summary: Fatty acids play crucial roles in plants as components of lipid membranes, sources of energy, and signaling molecules. Changes in LACS activity can lead to pleiotropic phenotypes. This review provides a comprehensive analysis of LACS family enzymes and highlights areas for future research.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Endocrinology & Metabolism
Xue-Jun Zhao, AI-Walid Mohsen, Stephanie Mihalik, Keaton Solo, Ermal Aliu, Huifang Shi, Shakuntala Basu, Catherine Kochersperger, Clinton Van't Land, Anuradha Karunanidhi, Kimberly A. Coughlan, Summar Siddiqui, Lisa M. Rice, Shawn Hillier, Eleonora Guadagnin, Paloma H. Giangrande, Paolo G. V. Martini, Jerry Vockley
Summary: Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a genetic disease affecting the heart, liver, and skeletal muscle. Treatment using synthetic human VLCAD mRNA and lipid nanoparticle encapsulated hVLCAD mRNA (LNP-VLCAD) can generate functional VLCAD enzyme in patient cells and improve the metabolic effects of the deficiency.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Medicine, General & Internal
Patricia Alcaide, Isaac Ferrer-Lopez, Leticia Gutierrez, Fatima Leal, Elena Martin-Hernandez, Pilar Quijada-Fraile, Marcello Bellusci, Ana Morais, Consuelo Pedron-Giner, Dolores Rausell, Patricia Correcher, Maria Unceta, Sinziana Stanescu, Magdalena Ugarte, Pedro Ruiz-Sala, Belen Perez
Summary: This study analyzed the newborn screening and confirmatory test results of 40 individuals and classified patients into two groups based on their acylcarnitine profiles, genetic findings, and residual enzyme activities. The results showed that a combined evaluation of these factors is useful in predicting disease severity and guiding treatment decisions.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Veronika Mater, Sabine Eisner, Cornelia Seidel, Dirk Schneider
Summary: Tuberculosis, a common infectious disease, infects about one-fourth of the global population. The causative agent, Mycobacterium tuberculosis, can enter a dormant state and display antibiotic resistance. The study investigates the membrane association and substrate specificity of MbFACL6, a potential target for treating resistant strains. MbFACL6 is found to be a peripheral membrane-attached protein and shows a broad spectrum of substrate tolerance.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Agricultural Engineering
Qinglian Wu, Yong Jiang, Ying Chen, Min Liu, Xian Bao, Wanqian Guo
Summary: This review provides a comprehensive analysis of the opportunities and challenges in the production and application of medium chain fatty acids (MCFAs), including introduction and comparison of two microbial synthesis pathways, analysis of production bottlenecks and solutions, assessment of production strategies, and recommendations for future alternative production modes and research priorities.
BIORESOURCE TECHNOLOGY
(2021)
Article
Agricultural Engineering
Yanyan Zhang, Jiazhe Bai, Jiane Zuo
Summary: This study conducted a long-term anaerobic fermentation of food waste without external electron donors for efficient production of medium-chain fatty acids (MCFAs). The results showed that the highest concentration of total MCFAs reached 29,886.10 mg COD/L, with n-caproate being the primary product at a maximum concentration of 28,191.66 mg COD/L. Microbial composition analysis revealed the presence of Lactobacillus, Bifidobacterium, Sporanaerobacter, and Caproiciproducens as the core community throughout the process. Metagenomic analysis identified the reverse beta-oxidization (RBO) and fatty acid biosynthesis (FAB) pathways, with FAB pathway being the main CE pathway. Moreover, Unclassified_-f_Ruminococcaceae and Limosilactobacillus were found to be the main participants in the FAB pathway. This study provides valuable insights into MCFAs production from organic waste.
BIORESOURCE TECHNOLOGY
(2023)
Article
Fisheries
Marc Ramos-Llorens, Alberto Ribes-Navarro, Juan C. Navarro, Francisco Hontoria, Naoki Kabeya, Oscar Monroig
Summary: The study demonstrates that Artemia franciscana has a high elongation capacity but limited overall LC-PUFA biosynthesis due to the lack of an adequate complement of fatty acyl desaturases in its genome.
Article
Biochemistry & Molecular Biology
Sarah C. Gruenert, William Foster, Anke Schumann, Allan Lund, Christina Pontes, Sylvia Roloff, Natalie Weinhold, Wyatt W. Yue, Ali AlAsmari, Osama A. Obaid, Eissa Ali Faqeih, Lisa Stuebbe, Raina Yamamoto, Corinne Gemperle-Britschgi, Melanie Walter, Ute Spiekerkoetter, Sabrina Mackinnon, Joern Oliver Sass
Summary: Succinyl-CoA:3-oxoacid coenzyme A transferase deficiency (SCOTD) is a rare autosomal recessive disorder caused by mutations in OXCT1, leading to impaired ketone body utilization. Analysis of clinical, biochemical, and genetic data on 44 SCOTD patients revealed a wide range of symptom onset, with severe ketoacidotic episodes in all patients. Pathogenic variants in the SCOT protein may affect protein structures and biochemical consequences, contributing to the disorder. Metabolic crises in SCOTD can be life-threatening, highlighting the importance of early diagnosis and intervention.
Article
Endocrinology & Metabolism
Sara Tucci, Christine Wagner, Sarah C. Gruenert, Uta Matysiak, Natalie Weinhold, Jeannette Klein, Francesco Porta, Marco Spada, Andrea Bordugo, Giulia Rodella, Francesca Furlan, Anna Sajeva, Francesca Menni, Ute Spiekerkoetter
Summary: This study confirmed the diagnosis of MCADD through enzyme testing and genetic analysis, showing a correlation between C6 and C8 acylcarnitine species and MCAD activity and disease severity. Additionally, 20 new variants were identified and functionally classified based on their effect on enzyme function.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Endocrinology & Metabolism
Sarah C. Gruenert, Matthias Eckenweiler, Dorothea Haas, Martin Lindner, Konstantinos Tsiakas, Rene Santer, Sara Tucci, Ute Spiekerkoetter
Summary: Peripheral neuropathy is a common complication in patients with LCHAD/MTP deficiency, with a higher prevalence in MTP patients and earlier onset compared to LCHADD. Despite early diagnosis and treatment, prevention of neuropathy remains a challenge, impacting the quality of life for affected patients.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Endocrinology & Metabolism
Anke Schumann, Kristin Schaller, Veronique Belche, Markus Cybulla, Sarah C. Gruenert, Nicolai Moers, Joern O. Sass, Andres Kaech, Luciana Hannibal, Ute Spiekerkoetter
Summary: Fabry disease is an X-linked lysosomal storage disorder characterized by GLA enzyme deficiency and Gb3 accumulation. Research revealed disrupted mitochondrial function, enhanced metabolic demands, activation of autophagy, and high expression of Sirtuin1 in renal cells of FD patients. These findings suggest potential new therapeutic targets to enhance treatment efficacy.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Multidisciplinary Sciences
Yurong Cheng, Pascal Schlosser, Johannes Hertel, Peggy Sekula, Peter J. Oefner, Ute Spiekerkoetter, Johanna Mielke, Daniel F. Freitag, Miriam Schmidts, Florian Kronenberg, Kai-Uwe Eckardt, Ines Thiele, Yong Li, Anna Koettgen
Summary: This study explores the cumulative contribution of rare, exonic genetic variants on urine metabolite levels and identifies 30 genes related to inborn errors of metabolism, with shared expression in liver and kidney. By using in silico constraint-based modeling, the study correctly predicts the direction of metabolite changes, emphasizing the potential of linking population genetics to modeling.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, General & Internal
Sarah C. Grunert, Luciana Hannibal, Anke Schumann, Stefanie Rosenbaum-Fabian, Stefanie Beck-Wodl, Tobias B. Haack, Mona Grimmel, Miriam Bertrand, Ute Spiekerkoetter
Summary: The study reported novel homozygous splice site variants in two Turkish patients with GSD VI, leading to impaired protein stability. In the era of next generation sequencing, techniques like transcriptome analysis are crucial for confirming pathogenicity and determining personalized therapeutic measures based on genetic results.
Article
Medicine, General & Internal
Ute Spiekerkoetter, Heiko Krude
Summary: Neonatal screening in Germany detects metabolic diseases early, allowing for better development and a normal life. Approximately one in five newborns have positive screening findings, making prompt evaluation and treatment essential.
DEUTSCHES ARZTEBLATT INTERNATIONAL
(2022)
Article
Multidisciplinary Sciences
Anna-Lisa Sorg, Leon Bergfeld, Marietta Jank, Victor Corman, Ilia Semmler, Anna Goertz, Andreas Beyerlein, Eva Verjans, Norbert Wagner, Horst Von Bernuth, Fabian Lander, Katharina Weil, Markus Hufnagel, Ute Spiekerkoetter, Cho-Ming Chao, Lutz Naehrlich, Ania Carolina Muntau, Ulf Schulze-Sturm, Gesine Hansen, Martin Wetzke, Anna-Maria Jung, Tim Niehues, Susanne Fricke-Otto, Ulrich Von Both, Johannes Huebner, Uta Behrends, Johannes G. Liese, Christian Schwerk, Christian Drosten, Ruediger Von Kries, Horst Schroten
Summary: The study investigates the seroprevalence of SARS-CoV-2 infections in children in Germany. The results show an increasing trend of seropositivity over time, especially in children with migrant background. Children under three are more susceptible to infection, but the infection rate levels off later. Serologic testing provides a more valid estimate of infections compared to recalled infections.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Rens Peeters, Jorge Cuenca-Escalona, Esther A. Zaal, Anna T. Hoekstra, Anouk C. G. Balvert, Marcos Vidal-Manrique, Niek Blomberg, Sjoerd J. van Deventer, Rinke Stienstra, Julia Jellusova, Martin Giera, Luciana Hannibal, Ute Spiekerkoetter, Martin Ter Beest, Celia R. Berkers, Annemiek B. van Spriel
Summary: This study identifies CD37 as a crucial membrane protein that inhibits fatty acid metabolism in aggressive B-cell lymphoma. Deletion of CD37 leads to increased fatty acid oxidation and depletion of palmitate from serum. CD37 interacts with the fatty acid transporter FATP1 to inhibit the uptake of palmitate. Inhibition of CD37 results in the uptake and processing of exogenous palmitate into energy and essential building blocks for proliferation. Patients with CD37-negative lymphomas exhibit large lipid deposits and intracellular lipid droplets. Inhibition of carnitine palmitoyl transferase 1 A compromises viability and proliferation of CD37-deficient lymphomas.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Lennart Moritz, Katharina Klotz, Sarah Catharina Gruenert, Luciana Hannibal, Ute Spiekerkoetter
Summary: Phenylketonuria (PKU) is a common inborn error of metabolism caused by mutations in phenylalanine hydroxylase (PAH). PKU patients have elevated levels of phenylalanine and may experience intellectual disability. This study found distinct differences in metabolite profiles between PKU patients and healthy controls, as well as altered concentrations of metabolites in treated patients. The PKU submetabolome identified in this study reflects the effects of dietary adherence, compensatory metabolic pathways, and metabolic disturbances that cannot be corrected with diet. Potential therapeutic targets may be discovered to approximate the submetabolome of PKU patients to that of healthy controls and prevent long-term organ damage.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Endocrinology & Metabolism
Ulrike Muetze, Lucy Henze, Julian Schroeter, Florian Gleich, Martin Lindner, Sarah C. Gruenert, Ute Spiekerkoetter, Rene Santer, Eva Thimm, Regina Ensenauer, Johannes Weigel, Skadi Beblo, Maria Arelin, Julia B. Hennermann, Iris Marquardt, Peter Freisinger, Johannes Kraemer, Andrea Dieckmann, Natalie Weinhold, Katharina A. Schiergens, Esther M. Maier, Georg F. Hoffmann, Sven F. Garbade, Stefan Koelker
Summary: Newborn screening is useful in identifying individuals with rare diseases like isovaleric aciduria. In this study, metabolic decompensation in isovaleric aciduria was associated with higher levels of isovalerylcarnitine (C5) and urinary isovalerylglycine. The first screening sample and confirmatory testing can be reliable early predictors of the disease's clinical course.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Review
Endocrinology & Metabolism
Ute Spiekerkoetter, David Bick, Richard Scott, Henrietta Hopkins, Tanja Krones, Edith Sky Gross, James R. Bonham
Summary: Population newborn screening (NBS) for phenylketonuria started in the US in 1963, and advances in mass spectrometry led to the recognition of multiple disorders with a single test. With the development of genomic testing, the range of conditions recognized after birth has expanded significantly. Different organizations and research projects propose various genomic screening strategies, taking into account factors such as clear benefits and other types of benefits. Ethical considerations should be made regarding asymptomatic, mild, or late-onset presentations where pre-symptomatic treatment may not be necessary.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Editorial Material
Endocrinology & Metabolism
Ute Spiekerkoetter
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Nutrition & Dietetics
Siti Nurjanah, Albert Gerding, Marcel A. Vieira-Lara, Bernard Evers, Miriam Langelaar-Makkinje, Ute Spiekerkoetter, Barbara M. Bakker, Sara Tucci
Summary: Defects in mitochondrial fatty acid beta-oxidation impair energy homeostasis. Very-long-chain acyl-CoA dehydrogenase deficiency is the most common mitochondrial FAO disorder, causing hypoglycemia. Triheptanoin, a dietary treatment, can be metabolized into precursors for gluconeogenesis. Studying the role of gluconeogenesis in long-chain mitochondrial FAO defects, it was found that heptanoate effectively increased glucose production.
Article
Genetics & Heredity
Sarah C. Gruenert, Athanasia Ziagaki, Andre Heinen, Anke Schumann, Sara Tucci, Ute Spiekerkoetter, Miriam Schmidts
Summary: Riboflavin transporter 1 (RFVT1) deficiency is an ultrarare metabolic disorder caused by pathogenic variants in SLC52A1. Only five cases have been reported so far, with newborns and infants showing symptoms while adults are usually asymptomatic. We report two new cases with heterozygous SLC52A1 variants, expanding the clinical spectrum of RFVT1 deficiency and showing that symptomatic presentation in adulthood is possible.