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| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/METK1_HUMAN METK1_HUMAN] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. | | [https://www.uniprot.org/uniprot/METK1_HUMAN METK1_HUMAN] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. |
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| == Publication Abstract from PubMed ==
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| 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 S-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 Mat1a and related genes function as compensatory mechanisms for FA-dependent SAM depletion, revealing a biochemical feedback cycle between FA and SAM one-carbon units.
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| Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism.,Pham VN, Bruemmer KJ, Toh JDW, Ge EJ, Tenney L, Ward CC, Dingler FA, Millington CL, Garcia-Prieto CA, Pulos-Holmes MC, Ingolia NT, Pontel LB, Esteller M, Patel KJ, Nomura DK, Chang CJ Science. 2023 Nov 3;382(6670):eabp9201. doi: 10.1126/science.abp9201. Epub 2023 , Nov 3. PMID:37917677<ref>PMID:37917677</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| == References == | | == References == |
| <references/> | | <references/> |
