eprintid: 27157 rev_number: 8 eprint_status: archive userid: 2 dir: disk0/00/02/71/57 datestamp: 2026-02-04 23:30:20 lastmod: 2026-02-04 23:30:20 status_changed: 2026-02-04 23:30:20 type: article metadata_visibility: show creators_name: Zhao, Yuxuan creators_name: Liang, Jingyimei creators_name: Ma, Wanning creators_name: Xiao, Jianbo creators_name: Cao, Hui title: The SAM-m6A axis as an unexplored therapeutic hub for plant-derived regulation of disease metabolism ispublished: pub subjects: uneat_bm divisions: uneatlantico_produccion_cientifica full_text_status: public keywords: S-Adenosylmethionine N6-Methyladenosine Plant-derived bioactive compounds Tea Polyphenols Disease abstract: S-adenosylmethionine (SAM) is the main cellular methyl donor and a core product of one-carbon metabolism. Its balance with S-adenosylhomocysteine (SAH) defines methylation potential and shapes epigenetic and epitranscriptomic outputs. RNA N6-methyladenosine (m6A) directly depends on SAM and is controlled by a writer-reader-eraser system. This review summarizes how altered SAM supply, SAH accumulation, and shifts in the SAM/SAH ratio can reprogram m6A landscapes. These changes can occur in cancer, metabolic disease, inflammation, and neurodegeneration. We integrate metabolic control of SAM generation and consumption with regulation of METTL3/METTL14, WTAP and related cofactors, and the erasers FTO and ALKBH5. We also assess plant-derived bioactive compounds proposed to act on this coupling. Most phytochemicals do not behave as potent, selective m6A enzyme inhibitors. They more often act upstream by reshaping one-carbon metabolism, redox state, and protein expression. This profile contrasts with canonical synthetic inhibitors that block a single node with higher affinity and more predictable pharmacodynamics. Together, the evidence supports the SAM-m6A axis as a practical framework to connect nutrient state with RNA fate decisions. It also highlights key gaps for translation, including target engagement, dose-exposure alignment, and causal validation of m6A-dependent phenotypes. date: 2026-02 publication: Pharmacological Research volume: 225 pagerange: 108114 id_number: doi:10.1016/j.phrs.2026.108114 refereed: TRUE issn: 10436618 official_url: http://doi.org/10.1016/j.phrs.2026.108114 access: open language: en citation: Artículo Materias > Biomedicina Universidad Europea del Atlántico > Investigación > Artículos y libros Abierto Inglés S-adenosylmethionine (SAM) is the main cellular methyl donor and a core product of one-carbon metabolism. Its balance with S-adenosylhomocysteine (SAH) defines methylation potential and shapes epigenetic and epitranscriptomic outputs. RNA N6-methyladenosine (m6A) directly depends on SAM and is controlled by a writer-reader-eraser system. This review summarizes how altered SAM supply, SAH accumulation, and shifts in the SAM/SAH ratio can reprogram m6A landscapes. These changes can occur in cancer, metabolic disease, inflammation, and neurodegeneration. We integrate metabolic control of SAM generation and consumption with regulation of METTL3/METTL14, WTAP and related cofactors, and the erasers FTO and ALKBH5. We also assess plant-derived bioactive compounds proposed to act on this coupling. Most phytochemicals do not behave as potent, selective m6A enzyme inhibitors. They more often act upstream by reshaping one-carbon metabolism, redox state, and protein expression. This profile contrasts with canonical synthetic inhibitors that block a single node with higher affinity and more predictable pharmacodynamics. Together, the evidence supports the SAM-m6A axis as a practical framework to connect nutrient state with RNA fate decisions. It also highlights key gaps for translation, including target engagement, dose-exposure alignment, and causal validation of m6A-dependent phenotypes. metadata Zhao, Yuxuan; Liang, Jingyimei; Ma, Wanning; Xiao, Jianbo y Cao, Hui mail SIN ESPECIFICAR (2026) The SAM-m6A axis as an unexplored therapeutic hub for plant-derived regulation of disease metabolism. Pharmacological Research, 225. p. 108114. ISSN 10436618 document_url: http://repositorio.uneatlantico.es/id/eprint/27157/1/1-s2.0-S1043661826000290-main.pdf