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Review
. 2025 Mar;50(3):242-254.
doi: 10.1016/j.tibs.2024.12.009. Epub 2025 Jan 15.

Mechanisms and rationales of SAM homeostasis

Zheng Xing  1 , Benjamin P Tu  2
Affiliations
Review

Mechanisms and rationales of SAM homeostasis

Zheng Xing et al. Trends Biochem Sci. 2025 Mar.

Abstract

S-Adenosylmethionine (SAM) is the primary methyl donor for numerous cellular methylation reactions. Its central role in methylation and involvement with many pathways link its availability to the regulation of cellular processes, the dysregulation of which can contribute to disease states, such as cancer or neurodegeneration. Emerging evidence indicates that intracellular SAM levels are maintained within an optimal range by a variety of homeostatic mechanisms. This suggests that the need to maintain SAM homeostasis represents a significant evolutionary pressure across all kingdoms of life. Here, we review how SAM controls cellular functions at the molecular level and discuss strategies to maintain SAM homeostasis. We propose that SAM exerts a broad and underappreciated influence in cellular regulation that remains to be fully elucidated.

Keywords: S-adenosylmethionine (SAM); epigenetics; methionine; methyl-sink; methylation; one-carbon metabolism.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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