| Structural highlights
Disease
METK1_HUMAN Defects in MAT1A are the cause of methionine adenosyltransferase deficiency (MATD) [MIM:250850; also called MAT I/III deficiency. MATD is an inborn error of metabolism resulting in isolated hypermethioninemia. Most patients have no clinical abnormalities, although some neurologic symptoms may be present in rare cases with severe loss of methionine adenosyltransferase activity.[1] [2] [3] [4]
Function
METK1_HUMAN Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
Publication Abstract from PubMed
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.
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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ubagai T, Lei KJ, Huang S, Mudd SH, Levy HL, Chou JY. Molecular mechanisms of an inborn error of methionine pathway. Methionine adenosyltransferase deficiency. J Clin Invest. 1995 Oct;96(4):1943-7. PMID:7560086 doi:http://dx.doi.org/10.1172/JCI118240
- ↑ Chamberlin ME, Ubagai T, Mudd SH, Wilson WG, Leonard JV, Chou JY. Demyelination of the brain is associated with methionine adenosyltransferase I/III deficiency. J Clin Invest. 1996 Aug 15;98(4):1021-7. PMID:8770875 doi:10.1172/JCI118862
- ↑ Chamberlin ME, Ubagai T, Mudd SH, Levy HL, Chou JY. Dominant inheritance of isolated hypermethioninemia is associated with a mutation in the human methionine adenosyltransferase 1A gene. Am J Hum Genet. 1997 Mar;60(3):540-6. PMID:9042912
- ↑ Chamberlin ME, Ubagai T, Mudd SH, Thomas J, Pao VY, Nguyen TK, Levy HL, Greene C, Freehauf C, Chou JY. Methionine adenosyltransferase I/III deficiency: novel mutations and clinical variations. Am J Hum Genet. 2000 Feb;66(2):347-55. PMID:10677294 doi:10.1086/302752
- ↑ 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. Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism. Science. 2023 Nov 3;382(6670):eabp9201. PMID:37917677 doi:10.1126/science.abp9201
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