{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPyruvate carboxylase (PC) is a biotin‐dependent mitochondrial enzyme that catalyzes the ATP‐driven conversion of pyruvate to oxaloacetate—a reaction central to anaplerosis, gluconeogenesis, lipogenesis, and the maintenance of the tricarboxylic acid (TCA) cycle. Structural investigations have detailed its complex multi‐domain organization (including the biotin carboxylase, carboxyltransferase, tetramerization, and biotin–carboxyl carrier protein domains), providing insights into its catalytic mechanism and the importance of oligomerization for full enzymatic activity. Tissue–specific regulation—illustrated by alternative promoter usage in pancreatic β–cells, its abundant presence in skeletal muscle, and its emerging role in supporting ATP‐linked respiration in brown adipocytes—underscores PC’s critical role in normal cellular metabolism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer biology, enhanced PC activity has been repeatedly implicated as a key metabolic adaptation to support rapid cell proliferation and metastasis. Up‐regulation of PC in non–small–cell lung cancer, breast cancer metastases, IDH1 mutant gliomas, and invasive breast cancer promotes anaplerosis that fosters lipid and nucleotide biosynthesis, sustains redox homeostasis, and facilitates survival under nutrient stress. In addition, PC overexpression in colorectal, ovarian, gastric, and prostate tumors—as well as in certain brain tumors such as astrocytomas and glioblastomas—has been linked to tumor progression via modulation of the extracellular matrix (for example, by supporting collagen production in tumor–associated fibroblasts) and by adapting to unique microenvironmental conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in the PC gene result in a spectrum of inherited metabolic disorders—ranging from neonatal lethal lactic acidosis to more chronic, milder presentations marked by developmental delay—highlighting its essential role in metabolic homeostasis. Molecular characterizations have unraveled a diverse mutation landscape (including missense, deletion, and splice–site alterations) with complex genotype–phenotype correlations. Beyond its metabolic functions, PC also contributes to innate immune responses by modulating NF–κB signaling during viral infections and may influence neuronal excitability associated with tumor–related seizures. Moreover, its roles in the liver, brain, and adipose tissue emphasize how perturbations in PC activity can affect whole–body energy and substrate fluxes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "25"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Katherine Sellers, Matthew P Fox, Michael Bousamra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI72873"}], "href": "https://doi.org/10.1172/JCI72873"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25607840"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25607840"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Stefan Christen, Doriane Lorendeau, Roberta Schmieder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Breast Cancer-Derived Lung Metastases Show Increased Pyruvate Carboxylase-Dependent Anaplerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2016.09.042"}], "href": "https://doi.org/10.1016/j.celrep.2016.09.042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27732858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27732858"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Song Xiang, Liang Tong "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.1393"}], "href": "https://doi.org/10.1038/nsmb.1393"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18297087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18297087"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "M J MacDonald, M J Longacre, E-C Langberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-009-1319-6"}], "href": "https://doi.org/10.1007/s00125-009-1319-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19296078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19296078"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dirk Roosterman, Graeme Stuart Cottrell "}, {"type": "b", "children": [{"type": "t", "text": "Rethinking the Citric Acid Cycle: Connecting Pyruvate Carboxylase and Citrate Synthase to the Flow of Energy and Material."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22020604"}], "href": "https://doi.org/10.3390/ijms22020604"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33435350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33435350"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ansaya Thonpho, Pinnara Rojvirat, Sarawut Jitrapakdee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the distal promoter of the human pyruvate carboxylase gene in pancreatic beta cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0055139"}], "href": "https://doi.org/10.1371/journal.pone.0055139"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23383084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23383084"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ariane D Minet, Michael Gaster "}, {"type": "b", "children": [{"type": "t", "text": "Pyruvate carboxylase is expressed in human skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2010.08.102"}], "href": "https://doi.org/10.1016/j.bbrc.2010.08.102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20807508"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20807508"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Udom Lao-On, Timothy S Cliff, Stephen Dalton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyruvate carboxylase supports basal ATP-linked respiration in human pluripotent stem cell-derived brown adipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2021.06.096"}], "href": "https://doi.org/10.1016/j.bbrc.2021.06.096"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34245978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34245978"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Aparna Shinde, Tomasz Wilmanski, Hao Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyruvate carboxylase supports the pulmonary tropism of metastatic breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13058-018-1008-9"}], "href": "https://doi.org/10.1186/s13058-018-1008-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30005601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30005601"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jose L Izquierdo-Garcia, Larry M Cai, Myriam M Chaumeil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glioma cells with the IDH1 mutation modulate metabolic fractional flux through pyruvate carboxylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0108289"}], "href": "https://doi.org/10.1371/journal.pone.0108289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25243911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25243911"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Phatchariya Phannasil, Israr-Ul H Ansari, Mahmoud El Azzouny, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mass spectrometry analysis shows the biosynthetic pathways supported by pyruvate carboxylase in highly invasive breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Basis Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2016.11.021"}], "href": "https://doi.org/10.1016/j.bbadis.2016.11.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27890529"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27890529"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Simon Schwörer, Natalya N Pavlova, Francesco V Cimino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fibroblast pyruvate carboxylase is required for collagen production in the tumour microenvironment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Metab (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42255-021-00480-x"}], "href": "https://doi.org/10.1038/s42255-021-00480-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34764457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34764457"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jarunya Ngamkham, Chanitra Thuwajit, Peti Thuwajit, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of Pyruvate Carboxylase Is Correlated With Colorectal Cancer Progression and Supports Growth of Invasive Colon Cancer HT-29 Cell Line."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21873/anticanres.14649"}], "href": "https://doi.org/10.21873/anticanres.14649"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33109566"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33109566"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Hongkai Shang, Jianfeng Zheng, Jinyi Tong "}, {"type": "b", "children": [{"type": "t", "text": "Integrated analysis of transcriptomic and metabolomic data demonstrates the significant role of pyruvate carboxylase in the progression of ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.104004"}], "href": "https://doi.org/10.18632/aging.104004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33177242"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33177242"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Eduard Gondáš, Alžbeta Kráľová Trančíková, Zuzana Majerčíková, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of pyruvate carboxylase in cultured human astrocytoma, glioblastoma and neuroblastoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gen Physiol Biophys (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/gpb_2021003"}], "href": "https://doi.org/10.4149/gpb_2021003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33880999"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33880999"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Jianqin Kang, Shanhong Tang, Guohong Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Expression and clinical significance of pyruvate carboxylase in gastric adenocarcinoma]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi (2013)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23294723"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23294723"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Chen Wang, Didi Zhao, Xing Shu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protective effects of all-trans retinoic acid against gastric premalignant lesions by repressing exosomal LncHOXA10-pyruvate carboxylase axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-021-03820-2"}], "href": "https://doi.org/10.1007/s00432-021-03820-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34632533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34632533"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Eduard Gondas, Mark Hives, Jan Kliment, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ubiquitous expression of pyruvate carboxylase among human prostate tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bratisl Lek Listy (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/BLL_2022_077"}], "href": "https://doi.org/10.4149/BLL_2022_077"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35907054"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35907054"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Dong Wang, Hong Yang, Kevin C De Braganca, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The molecular basis of pyruvate carboxylase deficiency: mosaicism correlates with prolonged survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2008.06.006"}], "href": "https://doi.org/10.1016/j.ymgme.2008.06.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18676167"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18676167"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Sophie Monnot, Valérie Serre, Bernadette Chadefaux-Vekemans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.20908"}], "href": "https://doi.org/10.1002/humu.20908"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19306334"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19306334"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Mary Anna Carbone, Derek A Applegarth, Brian H Robinson "}, {"type": "b", "children": [{"type": "t", "text": "Intron retention and frameshift mutations result in severe pyruvate carboxylase deficiency in two male siblings."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.10093"}], "href": "https://doi.org/10.1002/humu.10093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12112657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12112657"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Zhongying Cao, Yaqin Zhou, Shengli Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyruvate Carboxylase Activates the RIG-I-like Receptor-Mediated Antiviral Immune Response by Targeting the MAVS signalosome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep22002"}], "href": "https://doi.org/10.1038/srep22002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26906558"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26906558"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Manuel Schiff, Virginie Levrat, Cécile Acquaviva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A case of pyruvate carboxylase deficiency with atypical clinical and neuroradiological presentation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2005.10.007"}], "href": "https://doi.org/10.1016/j.ymgme.2005.10.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16325442"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16325442"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Emanuele G Coci, Vytautas Gapsys, Natasha Shur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyruvate carboxylase deficiency type A and type C: Characterization of five novel pathogenic variants in PC and analysis of the genotype-phenotype correlation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.23742"}], "href": "https://doi.org/10.1002/humu.23742"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30870574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30870574"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Mary Anna Carbone, Brian H Robinson "}, {"type": "b", "children": [{"type": "t", "text": "Expression and characterization of a human pyruvate carboxylase variant by retroviral gene transfer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20021397"}], "href": "https://doi.org/10.1042/BJ20021397"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12437512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12437512"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Fereshteh Maryami, Elham Rismani, Elham Davoudi-Dehaghani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In silico Analysis of Two Novel Variants in the Pyruvate Carboxylase (PC) Gene Associated with the Severe Form of PC Deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Iran Biomed J (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.61186/ibj.27.5.307"}], "href": "https://doi.org/10.61186/ibj.27.5.307"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37873728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37873728"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Anna Maria Buccoliero, Chiara Caporalini, Selene Moscardi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leat-associated seizures the possible role of EAAT2, pyruvate carboxylase and glutamine synthetase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsy Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.eplepsyres.2023.107258"}], "href": "https://doi.org/10.1016/j.eplepsyres.2023.107258"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38086219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38086219"}]}]}]}