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- W2802108667 abstract "Dysregulated metabolism has long been noticed in patients of psoriasis, especially enhanced amino acid metabolic activity. We found that in epidermis of psoriasis patients down-regulated serine paralleled with activated one-carbon metabolism. One-carbon metabolism is an important metabolic pathway involving not only sulfur amino acids like taurine, homocysteine and methionine et al, but also methylation metabolism. Acetyl-11-keto-β-boswellic acid (AKBA) is the most bioactive ingredient of the ancient folk medicine boswellic acids. It has been approved potentials in various inflammatory diseases including psoriasis and tumors. Here we show that AKBA can directly interact with methionine adenosyltransferase 2A (MAT2A) and inhibit the enzyme activity in both biochemical and cellular level. Consequently, s-adenosylmethionine (SAM), the product of the enzymatic reaction, is decreased. AKBA reprograms one-carbon metabolism by interfering function of MAT2A. The output of one-carbon metabolism like lipid metabolism is also decreased with AKBA treatment, which unfuels the cellular proliferation in the progression of psoriasis. Furthermore, altered level of SAM affects methylation metabolism by decreasing histone methylation marker H3K27me3 to regulate gene expression. Taken together, this work reveals that AKBA inhibit MAT2A to reprogram one-carbon metabolism and shows potential in treating psoriasis." @default.
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- W2802108667 date "2018-05-01" @default.
- W2802108667 modified "2023-09-30" @default.
- W2802108667 title "1082 Identification of a natural inhibitor of one-carbon metabolism in keratinocytes" @default.
- W2802108667 doi "https://doi.org/10.1016/j.jid.2018.03.1095" @default.
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