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Regulation of homocysteine metabolism and methylation in human and mouse tissues
Author(s) -
Chen Natalie C.,
Yang Fan,
Capecci Louis M.,
Gu Ziyu,
Schafer Andrew I.,
Durante William,
Yang XiaoFeng,
Wang Hong
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-143651
Subject(s) - methyltransferase , cystathionine beta synthase , methylation , homocysteine , methionine synthase , hyperhomocysteinemia , biochemistry , biology , dna methylation , microbiology and biotechnology , enzyme , methionine , gene expression , gene , amino acid , cysteine
Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine (Hcy) metabolism involves multiple enzymes; however, tissue Hcy metabolism and its relevance to methylation remain unknown. Here, we established gene expression profiles of 8 Hcy metabolic and 12 methylation enzymes in 20 human and 19 mouse tissues through bioinformatic analysis using expression sequence tag clone counts in tissue cDNA libraries. We analyzed correlations between gene expression, Hcy, S ‐adenosylhomocysteine (SAH), and S ‐adenosylmethionine (SAM) levels, and SAM/SAH ratios in mouse tissues. Hcy metabolic and methylation enzymes were classified into two types. The expression of Type 1 enzymes positively correlated with tissue Hcy and SAH levels. These include cystathionine β‐synthase, cystathionine‐γ‐lyase, paraxonase 1, 5,10‐methylenetetrahydrofolate reductase, betaine:homocysteine methyltransferase, methionine adenosyl‐transferase, phosphatidylethanolamine N ‐methyltransferases and glycine N ‐methyltransferase. Type 2 enzyme expressions correlate with neither tissue Hcy nor SAH levels. These include SAH hydrolase, methionyl‐tRNA synthase, 5‐methyltetrahydrofolate:Hcy methyltransferase, S ‐adenosylmethionine decarboxylase, DNA methyltransferase 1/3a, isoprenylcysteine carboxyl methyltransferases, and histone‐lysine N ‐methyltransferase. SAH is the only Hcy metabolite significantly correlated with Hcy levels and methylation enzyme expression. We established equations expressing combined effects of methylation enzymes on tissue SAH, SAM, and SAM/SAH ratios. Our study is the first to provide panoramic tissue gene expression profiles and mathematical models of tissue methylation regulation.—Chen, N. C., Yang, F., Capecci, L. M., Gu, Z., Schafer, A. I., Durante, W., Yang, X.‐F., Wang, H. Regulation of homocysteine metabolism and methylation in human and mouse tissues. FASEB J . 24, 2804–2817 (2010). www.fasebj.org