Article
Genetics & Heredity
Yue Yu, Ruixue Shuai, Lili Liang, Wenjuan Qiu, Linghua Shen, Shengnan Wu, Haiyan Wei, Yongxing Chen, Chiju Yang, Peng Xu, Xigui Chen, Hui Zou, Jizhen Feng, Tingting Niu, Haili Hu, Jun Ye, Huiwen Zhang, Deyun Lu, Zhuwen Gong, Xia Zhan, Wenjun Ji, Xuefan Gu, Lianshu Han
Summary: The study found that different mutations in the MMUT gene are associated with the response to vitamin B12 treatment and also have an impact on the outcomes of healthy/developmental delay.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Pediatrics
Neerja Gupta, Mounika Endrakanti, Meenakshi Bhat, Nivedita Rao, Ravneet Kaur, Madhulika Kabra
Summary: This study investigated the clinical and molecular spectrum of Methylmalonic acidemia (MMA). A retrospective study was conducted on 30 MMA patients to evaluate their phenotype, biochemical abnormalities, genotype, and outcomes. The study found that MMA cblC subtype was the most common type of MMA, and the outcomes of MMA were influenced by the type of molecular defect, age, and severity of presentation.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Review
Endocrinology & Metabolism
Leah E. Venturoni, Charles P. Venditti
Summary: This article reviews pre-clinical studies on alternative approaches to solid organ transplantation as a treatment for MMUT MMA.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Review
Endocrinology & Metabolism
PamelaSara E. Head, Jordan L. Meier, Charles P. Venditti
Summary: Methylmalonic acidemia (MMA) is a severe inborn error of metabolism with limited treatment options. Aberrant acylation has been identified as a characteristic feature of MMA, suggesting that targeting posttranslational modifications may be a new therapeutic approach.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Genetics & Heredity
Sitao Li, Congcong Shi, Yao Cai, Xia Gu, Hui Xiong, Xiaoyu Liu, Yinchun Zhang, Xin Xiao, Fei Ma, Hu Hao
Summary: This study analyzed the differential proteome of serum between isolated MMA patients and healthy controls, and identified 94 differentially expressed proteins (DEPs). The DEPs were mainly associated with immune-related function, membrane protein-related function, lysosome, and cholesterol metabolism pathways. The findings of this study contribute to understanding MMA and may be useful for developing alternative therapies.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Olga M. Sokolovskaya, Tanja Plessl, Henry Bailey, Sabrina Mackinnon, Matthias R. Baumgartner, Wyatt W. Yue, D. Sean Froese, Michiko E. Taga
Summary: This study examined the impact of various cobamide cofactors on the function of MMUT and found differences in how they support the enzyme, as well as variations in the catalytic rescue of disease-associated MMUT variants. The findings challenge the sole focus on cobalamin in human physiology, suggesting that diverse cobamides can play a role in supporting human enzyme function.
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)
Article
Genetics & Heredity
Rokeya Begum, Abu Ashfaqur Sajib, A. B. M. Khademul Islam, Suprovath Kumar Sarker, Mohammad Sazzadul Islam, Narayan Saha, Kaiissar Mannoor, Firdausi Qadri, Sharif Akhteruzzaman
Summary: Methylmalonic acidemia (MMA) is a rare disorder caused by mutations in the MUT gene. This study identified two new MUT gene mutations and suggested that one of them may have disease-causing effects. Furthermore, distinct metabolic features were found to differentiate between MMA patients and healthy controls.
Review
Agriculture, Dairy & Animal Science
C. L. Girard, M. Duplessis
Summary: The rumen microbiota can synthesize sufficient B vitamins to prevent clinical deficiency symptoms in dairy cows. However, subclinical deficiency can lead to reduced metabolic efficiency and lower milk production.
Article
Biochemical Research Methods
Wang Ma, Xin Li, Feng Zhang, Zi-Yi Zhang, Wen-Qian Yang, Peng-Wei Huang, Yang Gu, Xiao-Man Sun
Summary: In this study, propionate wastewater (PW), a widespread industrial and domestic wastewater, was used as a substrate for Schizochytrium sp. to produce docosahexaenoic acid (DHA)-rich lipid. The overexpression of methylmalonyl-CoA mutase (MCM) in Schizochytrium sp. enhanced the metabolism of propionate, allowing the engineered strain to effectively utilize PW. Experiments showed that the engineered strain can completely replace clean water with PW containing 5 g L-1 propionate, and in fed-batch fermentation, it achieved higher biomass and lipid yield compared to the wild type. The overexpression of MCM promoted DHA and lipid accumulation by inducing ATP synthesis and enhancing the antioxidant capacity of cells. PW can thus be considered as an effective and economical substrate and water source for DHA production by Schizochytrium sp.
BIOTECHNOLOGY JOURNAL
(2023)
Article
Endocrinology & Metabolism
Emmanuel Scalais, Christine Geron, Charlotte Pierron, Sandra Cardillo, Vincent Schlesser, Frederic Mataigne, Patricia Borde, Luc Regal
Summary: Hydroxocobalamin dose-intensification (OHCBL-DI) improved biochemical and clinical outcome in patients with early-onset cblC deficiency. Pathogenic variants in MMACHC disrupt the synthesis of methyl-cobalamin and 5'-deoxyadenosyl-cobalamin, which are important cofactors for methionine synthase and methyl-malonyl-CoA mutase enzymes. By bypassing MMACHC and utilizing methionine synthase reductase and adenosyltransferase, OHCBL-DI improves cognitive and retinal function.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Chemistry, Physical
Arghya Pratim Ghosh, Megan J. Toda, Pawel M. Kozlowski
Summary: The study examines the mechanism of how the environment affects the triggering of Co-C-5 bond cleavage in enzymes by calculating the bond dissociation energy. It is found that the presence or absence of substrate does not substantially impact the energy barrier for Co-C-5 bond cleavage, and indicates the crucial role of Tyrosine 105 in facilitating the cleavage of the Co-C-5 bond.
Article
Medicine, General & Internal
Berna Seker Yilmaz, Deniz Kor, Fatma Derya Bulut, Sebile Kilavuz, Serdar Ceylaner, Halise Neslihan Onenli Mungan
Summary: This study summarized the clinical and molecular findings based on long-term follow up of 37 Turkish patients with isolated MMA, identifying two novel mutations including one splice-site mutation in the MUT gene and one frame shift mutation in the MMAA gene. The most common clinical complications observed were growth retardation, renal involvement, mental motor retardation, and developmental delay.
TURKISH JOURNAL OF MEDICAL SCIENCES
(2021)
Article
Medicine, Research & Experimental
Randy J. Chandler, Giovanni Di Pasquale, Eun-Young Choi, David Chang, Stephanie N. Smith, Jennifer L. Sloan, Victoria Hoffmann, Lina Li, John A. Chiorini, Charles P. Venditti
Summary: In this study, the therapeutic efficacy of AAV44.9 vector in treating propionic acidemia (PA) was evaluated using a new mouse model. The results showed that a single injection of AAV44.9 vector at birth improved survival, reduced plasma methylcitrate, and resulted in high levels of transgene expression in the liver and heart. These findings suggest the potential of AAV44.9 vector for the treatment of metabolic disorders.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Review
Food Science & Technology
Marie Joncquel Chevalier-Curt, Guillaume Grzych, Celine Trad, Julien Lannoy, Sylvie Deheul, Riyad Hanafi, Claire Douillard, Joseph Vamecq
Summary: Nitrous oxide (N2O) abuse can result in pathological changes, affecting DNA/RNA/protein methylation and impairing enzyme function related to myelinogenesis and myelopathy. N2O abuse leads to impairment of vitamin-B12-dependent pathways and impacts multiple metabolic pathways, leading to various potential research/laboratory markers.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Genetics & Heredity
Diana Gallego, Fatima Leal, Alejandra Gamez, Margarita Castro, Rosa Navarrete, Obdulia Sanchez-Lijarcio, Isidro Vitoria, Maria Bueno-Delgado, Amaya Belanger-Quintana, Ana Morais, Consuelo Pedron-Giner, Inmaculada Garcia, Jaume Campistol, Rafael Artuch, Carlos Alcaide, Veronica Cornejo, David Gil, Raquel Yahyaoui, Lourdes R. Desviat, Magdalena Ugarte, Aurora Martinez, Belen Perez
Article
Medical Laboratory Technology
Alejandro Fulgencio-Covian, Esmeralda Alonso-Barroso, Adam J. Guenzel, Ana Rivera-Barahona, Magdalena Ugarte, Belen Perez, Michael A. Barry, Celia Perez-Cerda, Eva Richard, Lourdes R. Desviat
TRANSLATIONAL RESEARCH
(2020)
Article
Genetics & Heredity
Alicia Hillert, Yair Anikster, Amaya Belanger-Quintana, Alberto Burlina, Barbara K. Burton, Carla Carducci, Ana E. Chiesa, John Christodoulou, Maja Dordevic, Lourdes R. Desviat, Aviva Eliyahu, Roeland A. F. Evers, Lena Fajkusova, Francois Feillet, Pedro E. Bonfim-Freitas, Maria Gizewska, Polina Gundorova, Daniela Karall, Katya Kneller, Sergey Kutsev, Vincenzo Leuzzi, Harvey L. Levy, Uta Lichter-Konecki, Ania C. Muntau, Fares Namour, Mariusz Oltarzewski, Andrea Paras, Belen Perez, Emil Polak, Alexander Polyakov, Francesco Porta, Marianne Rohrbach, Sabine Scholl-Burgi, Norma Specola, Maja Stojiljkovic, Nan Shen, Luiz C. Santana-da Silva, Anastasia Skouma, Francjan van Spronsen, Vera Stoppioni, Beat Thony, Friedrich K. Trefz, Jerry Vockley, Youngguo Yu, Johannes Zschocke, Georg F. Hoffmann, Sven F. Garbade, Nenad Blau
AMERICAN JOURNAL OF HUMAN GENETICS
(2020)
Article
Biochemistry & Molecular Biology
A. Vilas, P. Yuste-Checa, D. Gallego, L. R. Desviat, M. Ugarte, C. Perez-Cerda, A. Gamez, B. Perez
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2020)
Article
Biochemistry & Molecular Biology
Esmeralda Alonso-Barroso, Belen Perez, Lourdes Ruiz Desviat, Eva Richard
Summary: Propionic acidemia (PA) is a common life-threatening organic acidemia caused by mutations in PCCA or PCCB genes. Cardiac alterations are a major cause of mortality in PA patients. Study using iPSC derived cardiomyocytes from a PA patient showed characteristics such as reduced oxygen consumption and endoplasmic reticulum stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Alejandro Fulgencio-Covian, Mar Alvarez, Barry A. Pepers, Aristides Lopez-Marquez, Magdalena Ugarte, Belen Perez, Willeke M. C. van Roon-Mom, Lourdes R. Desviat, Eva Richard
STEM CELL RESEARCH
(2020)
Review
Cardiac & Cardiovascular Systems
Kyung Chan Park, Steve Krywawych, Eva Richard, Lourdes R. Desviat, Pawel Swietach
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2020)
Review
Medicine, Research & Experimental
Suzan M. Hammond, Annemieke Aartsma-Rus, Sandra Alves, Sven E. Borgos, Ronald A. M. Buijsen, Rob W. J. Collin, Giuseppina Covello, Michela A. Denti, Lourdes R. Desviat, Lucia Echevarria, Camilla Foged, Gisela Gaina, Alejandro Garanto, Aurelie T. Goyenvalle, Magdalena Guzowska, Irina Holodnuka, David R. Jones, Sabine Krause, Taavi Lehto, Marisol Montolio, Willeke Van Roon-Mom, Virginia Arechavala-Gomeza
Summary: The field of nucleic acid-based therapeutics has seen rapid development in recent years, with the main challenge being delivery to target tissues. The adoption of delivery technologies, such as conjugates or nanoparticles, has been a game changer for many therapeutic indications.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Ainhoa Martinez-Pizarro, Fatima Leal, Lise Lolle Holm, Thomas K. Doktor, Ulrika S. S. Petersen, Maria Bueno, Beat Thony, Belen Perez, Brage S. Andresen, Lourdes R. Desviat
Summary: We report the identification of two new splicing variants of 6-pyruvoyl-tetrahydropterin synthase in a patient with tetrahydrobiopterin deficiency. These variants were found to cause the inclusion of abnormal pseudoexons, leading to hyperphenylalaninemia and monoamine neurotransmitter deficiency. Antisense oligonucleotides were designed to correct the aberrant pseudoexon inclusion, demonstrating the therapeutic potential of this approach.
NUCLEIC ACID THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Mar Alvarez, Pedro Ruiz-Sala, Belen Perez, Lourdes Ruiz Desviat, Eva Richard
Summary: Propionic acidemia (PA) disorder primarily affects the heart and leads to cardiac complications due to the accumulation of toxic metabolites. Cardiomyocytes generated from induced pluripotent stem cells (iPSCs) derived from a PA patient were used to study microRNAs (miRNAs) profiles and cellular pathways associated with PA cardiac phenotypes. The study identified upregulated cardiac-enriched miRNAs and alterations in various cellular pathways, providing insights into the molecular mechanisms of this rare disease and potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)