Formaldehyde regulates <i>S</i>-adenosylmethionine biosynthesis and one-carbon metabolism.
basic_science · Level V
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- Record sourced from PubMed, PMID 37917677.
- Also identified by DOI 10.1126/science.abp9201 and PMC identifier 11500418.
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Abstract
One-carbon metabolism is an essential branch of cellular metabolism that intersects with epigenetic regulation. In this work, we show how formaldehyde (FA), a one-carbon unit derived from both endogenous sources and environmental exposure, regulates one-carbon metabolism by inhibiting the biosynthesis of <i>S</i>-adenosylmethionine (SAM), the major methyl donor in cells. FA reacts with privileged, hyperreactive cysteine sites in the proteome, including Cys120 in S-adenosylmethionine synthase isoform type-1 (MAT1A). FA exposure inhibited MAT1A activity and decreased SAM production with MAT-isoform specificity. A genetic mouse model of chronic FA overload showed a decrease n SAM and in methylation on selected histones and genes. Epigenetic and transcriptional regulation of <i>Mat1a</i> and related genes function as compensatory mechanisms for FA-dependent SAM depletion, revealing a biochemical feedback cycle between FA and SAM one-carbon units.
Medical subject headings
- Carbon
- Epigenesis, Genetic
- S-Adenosylmethionine
- Formaldehyde
- Methionine Adenosyltransferase
- Cysteine