{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPHGDH is the rate‐limiting enzyme that diverts the glycolytic intermediate 3‐phosphoglycerate into the serine biosynthesis pathway, a process critical for generating serine, glycine, nucleotides, and key tricarboxylic acid cycle intermediates. In several human cancers—including breast, melanoma, pancreatic, lung, and renal carcinomas—elevated PHGDH expression and gene amplification have been shown to drive increased metabolic flux toward serine production, thereby supporting rapid cell proliferation, survival under low‐serine conditions, and metabolic reprogramming (for example, by fueling redox balance and anaplerosis). These studies also reveal that enhanced PHGDH activity underpins aggressive tumor phenotypes, cancer stem‐like properties, and even drug resistance, as demonstrated by its involvement in Sorafenib resistance in hepatocellular carcinoma and its requirement for mTORC1‐mediated growth signaling in metastatic lesions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its metabolic function, PHGDH is subject to multiple layers of regulation that modulate its enzymatic activity and, consequently, tumor behavior. Post‐translational modifications such as ubiquitination and monoubiquitination—as mediated by factors like Parkin and specific E3 ligase complexes—can either target PHGDH for proteasomal degradation or enhance its activity to promote metastatic progression. Other regulatory mechanisms include control by noncoding RNAs and histone modifiers (for instance, through modulation by KDM4B), as well as inhibitory strategies using small molecules like oridonin that bind novel allosteric sites. Together, these modifications affect not only serine and nucleotide metabolism but also redox homeostasis and pro‐survival signaling pathways, suggesting that PHGDH is an attractive target for combination therapies in cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in oncogenesis, altered PHGDH function is implicated in diverse developmental and non‐malignant conditions. Inherited loss‐of‐function mutations in PHGDH cause severe serine‐deficiency disorders such as Neu–Laxova syndrome, characterized by multiple congenital anomalies and perinatal lethality, while defects in serine metabolism have also been associated with neurologic and retinal degenerative conditions. Furthermore, PHGDH regulation is important in normal physiology—for example, in endometrial differentiation and in skeletal muscle where PHGDH activity supports protein synthesis and mTORC1 signaling. Alterations in local tissue metabolism, as observed in fibrotic diseases and even in varicocele‐associated infertility, further underscore the broad functional impact of PHGDH in maintaining cellular and tissue homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Richard Possemato, Kevin M Marks, Yoav D Shaul, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "High level PHGDH expression in breast is predominantly associated with keratin 5-positive cell lineage independently of malignancy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molonc.2015.05.003"}], "href": "https://doi.org/10.1016/j.molonc.2015.05.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26026368"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26026368"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shinkyo Yoon, Jong Gwang Kim, An Na Seo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical Implication of Serine Metabolism-Associated Enzymes in Colon Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000439571"}], "href": "https://doi.org/10.1159/000439571"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26439504"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26439504"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Boxi Zhang, Adi Zheng, Per Hydbring, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHGDH Defines a Metabolic Subtype in Lung Adenocarcinomas with Poor Prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2017.05.067"}], "href": "https://doi.org/10.1016/j.celrep.2017.05.067"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28614715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28614715"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hirofumi Yoshino, Nijiro Nohata, Kazutaka Miyamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHGDH as a Key Enzyme for Serine Biosynthesis in HIF2α-Targeting Therapy for Renal Cell Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-17-1589"}], "href": "https://doi.org/10.1158/0008-5472.CAN-17-1589"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28951458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28951458"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zhiwang Song, Chan Feng, Yonglin Lu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Phosphoglycerate dehydrogenase inhibition induces p-mTOR-independent autophagy and promotes multilineage differentiation in embryonal carcinoma stem-like cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-0997-8"}], "href": "https://doi.org/10.1038/s41419-018-0997-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30250195"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30250195"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Mark R Sullivan, Katherine R Mattaini, Emily A Dennstedt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased Serine Synthesis Provides an Advantage for Tumors Arising in Tissues Where Serine Levels Are Limiting."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2019.02.015"}], "href": "https://doi.org/10.1016/j.cmet.2019.02.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30905671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30905671"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Lai Wei, Derek Lee, Cheuk-Ting Law, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Serine synthesis through PHGDH coordinates nucleotide levels by maintaining central carbon metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-07868-6"}], "href": "https://doi.org/10.1038/s41467-018-07868-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30575741"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30575741"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Hirofumi Yoshino, Hideki Enokida, Yoichi Osako, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of PHGDH expression in bladder cancer: potential targeting therapy with gemcitabine/cisplatin and the contribution of promoter DNA hypomethylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12697"}], "href": "https://doi.org/10.1002/1878-0261.12697"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32386122"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32386122"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Min Ji Jeon, Mi-Hyeon You, Ji Min Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High Phosphoglycerate Dehydrogenase Expression Induces Stemness and Aggressiveness in Thyroid Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thyroid (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/thy.2020.0105"}], "href": "https://doi.org/10.1089/thy.2020.0105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32438862"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32438862"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Gianmarco Rinaldi, Erica Pranzini, Joke Van Elsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In Vivo Evidence for Serine Biosynthesis-Defined Sensitivity of Lung Metastasis, but Not of Primary Breast Tumors, to mTORC1 Inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2020.11.027"}], "href": "https://doi.org/10.1016/j.molcel.2020.11.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33340488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33340488"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Hanyu Xu, Xiaoyu Qing, Qian Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dimerization of PHGDH via the catalytic unit is essential for its enzymatic function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2021.100572"}], "href": "https://doi.org/10.1016/j.jbc.2021.100572"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33753166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33753166"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Kevin Eade, Marin L Gantner, Joseph A Hostyk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serine biosynthesis defect due to haploinsufficiency of PHGDH causes retinal disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Metab (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42255-021-00361-3"}], "href": "https://doi.org/10.1038/s42255-021-00361-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33758422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33758422"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Yuping Tan, Xia Zhou, Yanqiu Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biophysical and biochemical properties of PHGDH revealed by studies on PHGDH inhibitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-021-04022-2"}], "href": "https://doi.org/10.1007/s00018-021-04022-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34971423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34971423"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Kui Wang, Li Luo, Shuyue Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-023-36708-5"}], "href": "https://doi.org/10.1038/s41467-023-36708-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36823188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36823188"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Xin-Yu Wang, Hong-Ming Li, Ran Xia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KDM4B down-regulation facilitated breast cancer cell stemness via PHGDH upregulation in H3K36me3-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-023-04777-1"}], "href": "https://doi.org/10.1007/s11010-023-04777-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37249813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37249813"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Liliang Shen, Junfeng Zhang, Zongtai Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHGDH Inhibits Ferroptosis and Promotes Malignant Progression by Upregulating SLC7A11 in Bladder Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.74546"}], "href": "https://doi.org/10.7150/ijbs.74546"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36147463"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36147463"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Sanghamitra Dey, Rodney L Burton, Gregory A Grant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural analysis of substrate and effector binding in Mycobacterium tuberculosis D-3-phosphoglycerate dehydrogenase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi800212b"}], "href": "https://doi.org/10.1021/bi800212b"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18627175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18627175"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Tohru Ohnuma, Nobuto Shibata, Hitoshi Maeshima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association analysis of glycine- and serine-related genes in a Japanese population of patients with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prog Neuropsychopharmacol Biol Psychiatry (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pnpbp.2009.02.004"}], "href": "https://doi.org/10.1016/j.pnpbp.2009.02.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19223009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19223009"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Hongling Du, Danielle Vitiello, Jennifer L Sarno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "3-Phosphoglycerate dehydrogenase expression is regulated by HOXA10 in murine endometrium and human endometrial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reproduction (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/REP-08-0376"}], "href": "https://doi.org/10.1530/REP-08-0376"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19778996"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19778996"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Ranad Shaheen, Zuhair Rahbeeni, Amal Alhashem, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2014.04.015"}], "href": "https://doi.org/10.1016/j.ajhg.2014.04.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24836451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24836451"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Rocio Acuna-Hidalgo, Denny Schanze, Ariana Kariminejad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2014.07.012"}], "href": "https://doi.org/10.1016/j.ajhg.2014.07.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25152457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25152457"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Recep Nigdelioglu, Robert B Hamanaka, Angelo Y Meliton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transforming Growth Factor (TGF)-β Promotes de Novo Serine Synthesis for Collagen Production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.756247"}], "href": "https://doi.org/10.1074/jbc.M116.756247"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27836973"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27836973"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Thiago R Cavole, Eduardo Perrone, Felipe S C Lucena de Castro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical, molecular, and pathological findings in a Neu-Laxova syndrome stillborn: A Brazilian case report."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.61559"}], "href": "https://doi.org/10.1002/ajmg.a.61559"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32196970"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32196970"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Wen-Bin Guo, Zhen-Hui Huang, Cheng Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down regulating PHGDH affects the lactate production of sertoli cells in varicocele."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reprod Biol Endocrinol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12958-020-00625-9"}], "href": "https://doi.org/10.1186/s12958-020-00625-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32664979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32664979"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Woo-Cheol Sim, Wonseok Lee, Hyungtai Sim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of PHGDH expression and hepatic serine level contribute to the development of fatty liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metabolism (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.metabol.2019.154000"}], "href": "https://doi.org/10.1016/j.metabol.2019.154000"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31678070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31678070"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Sakari Mäntyselkä, Kalle Kolari, Philipp Baumert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serine synthesis pathway enzyme PHGDH is critical for muscle cell biomass, anabolic metabolism, and mTORC1 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00151.2023"}], "href": "https://doi.org/10.1152/ajpendo.00151.2023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37991454"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37991454"}]}]}]}