{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ISYNA1 encodes myo‐inositol‐1‐phosphate synthase, the rate‐limiting enzyme that converts glucose 6‐phosphate into myo‐inositol‐1‐phosphate, thereby initiating de novo myo‐inositol biosynthesis. This pathway is critical for generating myo‐inositol, the precursor for essential inositol lipids and signaling molecules involved in membrane biogenesis, osmoregulation, and stress responses. In mammalian tissues such as the testis, high ISYNA1 expression supports elevated inositol levels that may contribute to cellular osmotic balance and differentiation processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In mammalian cells, ISYNA1 expression is finely tuned by transcriptional regulators such as E2F1 and ETR101, with its promoter responsive to cell cycle– and stress‐related signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, negative regulation by inositol pyrophosphate kinase (IP6K1) further modulates inositol synthesis by downregulating ISYNA1 transcription, thereby linking cellular metabolism with epigenetic and metabolic control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of human disease, altered ISYNA1 expression has been implicated in cancer. For example, reduced ISYNA1 levels act as a tumor suppressor in pancreatic cancer, influencing cell cycle regulators such as p21 and invasion mediators like ZEB-1; similar dysregulation in bladder cancer correlates with increased proliferation and poorer prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In infectious organisms, such as the malaria parasite Plasmodium falciparum, the orthologous enzyme is essential not only for bulk phosphatidylinositol synthesis but also specifically for glycosylphosphatidylinositol (GPI) anchor formation, underscoring its vital role in parasite survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the field of metabolic engineering, enhanced activity of ISYNA1 (or its homologs) has been exploited to boost the production of valuable chemicals. Upregulation of this enzyme serves as a rate‐limiting step in pathways designed to produce D‑glucaric acid in yeast."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In plants, increased expression of ISYNA1 orthologs contributes to improved tolerance against various abiotic stresses—including salt, drought, and heavy metal exposure—by elevating the inositol pool necessary for cellular protection and antioxidant responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, in citrus, genetic variations in myo‐inositol‐1‐phosphate synthase have been associated with altered substrate binding and catalytic efficiency, which may affect cell wall metabolism and susceptibility to pathogen infection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight that ISYNA1 plays a multifaceted role in cell metabolism, signal transduction, stress adaptation, and disease modulation. Its regulation by diverse transcription factors and kinases, as well as its involvement in both normal physiology and pathological conditions, underscores the enzyme’s importance as a potential biomarker and therapeutic target across species.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Theodore R Chauvin, Michael D Griswold "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the expression and regulation of genes necessary for myo-inositol biosynthesis and transport in the seminiferous epithelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.103.022731"}], "href": "https://doi.org/10.1095/biolreprod.103.022731"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14613899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14613899"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ratnam S Seelan, Latha K Parthasarathy, Ranga N Parthasarathy "}, {"type": "b", "children": [{"type": "t", "text": "E2F1 regulation of the human myo-inositol 1-phosphate synthase (ISYNA1) gene promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Biochem Biophys (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.abb.2004.08.002"}], "href": "https://doi.org/10.1016/j.abb.2004.08.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15464731"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15464731"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tomoyuki Takaya, Kaori Kasatani, Syunsuke Noguchi, et al. 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