ジメチルグリシン脱水素酵素、ジメチルグリシンデヒドロゲナーゼ
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/12/15 14:07:50」(JST)
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English Journal
- Crystal structure of the histone lysine specific demethylase LSD1 complexed with tetrahydrofolate.
- Luka Z1, Pakhomova S, Loukachevitch LV, Calcutt MW, Newcomer ME, Wagner C.Author information 1Department of Biochemistry, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, United States.AbstractAn important epigenetic modification is the methylation/demethylation of histone lysine residues. The first histone demethylase to be discovered was a lysine-specific demethylase 1, LSD1, a flavin containing enzyme which carries out the demethylation of di- and monomethyllysine 4 in histone H3. The removed methyl groups are oxidized to formaldehyde. This reaction is similar to those performed by dimethylglycine dehydrogenase and sarcosine dehydrogenase, in which protein-bound tetrahydrofolate was proposed to serve as an acceptor of the generated formaldehyde. We showed earlier that LSD1 binds tetrahydrofolate with high affinity which suggests its possible participation in the histone demethylation reaction. In the cell, LSD1 interacts with CoREST, a co-repressor which binds REST (repressor element-1 silencing transcription). In order to elucidate the role of folate in the demethylating reaction we solved the crystal structure of the LSD1-CoREST-tetrahydrofolate complex. In the complex the folate-binding site is located in the active center in close proximity to FAD. This position of the folate suggests that the bound tetrahydrofolate accepts the formaldehyde generated in the course of histone demethylation to form 5,10-methylene-tetrahydrofolate. We also show the formation of 5,10-methylene-tetrahydrofolate during the course of the enzymatic reaction in the presence of tetrahydrofolate by mass spectrometry. Production of this form of folate could act to prevent accumulation of potentially toxic formaldehyde in the cell. These studies suggest that folate may play a role in the epigenetic control of gene expression in addition to its traditional role in the transfer of one-carbon units in metabolism.
- Protein science : a publication of the Protein Society.Protein Sci.2014 Apr 8. doi: 10.1002/pro.2469. [Epub ahead of print]
- An important epigenetic modification is the methylation/demethylation of histone lysine residues. The first histone demethylase to be discovered was a lysine-specific demethylase 1, LSD1, a flavin containing enzyme which carries out the demethylation of di- and monomethyllysine 4 in histone H3. The
- PMID 24715612
- Hepatotoxic constituents and toxicological mechanism of Xanthium strumarium L. fruits.
- Xue LM1, Zhang QY2, Han P3, Jiang YP2, Yan RD4, Wang Y2, Rahman K5, Jia M2, Han T6, Qin LP7.Author information 1Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China; Health Laboratory, Shanghai Municipal Center for Disease Control and Prevention, 1380 North Zhongshan Road, Shanghai 200336, People's Republic of China.2Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.3Center for Disease Control and Prevention, Jinan Military Region, PLA, 36 East Wenhua Road, Jinan, Shandong 250012, People's Republic of China.4The Second Affiliated Hospital of Shandong Traditional Chinese Medicine University, 1 Jingba Road, Ji'nan 250001, People's Republic of China.5Faculty of Science, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK.6Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: than927@163.com.7Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: qinsmmu@126.com.AbstractETHNOPHARMACOLOGICAL RELEVANCE: In the recent years, the international community has attached increasing importance to possible toxicity associated with Traditional Chinese Medicine (TCM). And hepatotoxicity is one of the major concerns, a fundamental pathological process induced by toxicant. This paper is in an attempt to identify the hepatotoxic components in Xanthium strumarium L. fruits (XSF) and interpret the toxicological mechanism induced by XSF.
- Journal of ethnopharmacology.J Ethnopharmacol.2014 Mar 14;152(2):272-82. doi: 10.1016/j.jep.2013.12.024. Epub 2014 Jan 18.
- ETHNOPHARMACOLOGICAL RELEVANCE: In the recent years, the international community has attached increasing importance to possible toxicity associated with Traditional Chinese Medicine (TCM). And hepatotoxicity is one of the major concerns, a fundamental pathological process induced by toxicant. This p
- PMID 24447814
- Osmotic regulation of hepatic betaine metabolism.
- Hoffmann L1, Brauers G, Gehrmann T, Häussinger D, Mayatepek E, Schliess F, Schwahn BC.Author information 1Department of General Paediatrics, University Children's Hospital, Heinrich-Heine-University, Duesseldorf, Germany.AbstractBetaine critically contributes to the control of hepatocellular hydration and provides protection of the liver from different kinds of stress. To investigate how the hepatocellular hydration state affects gene expression of enzymes involved in the metabolism of betaine and related organic osmolytes, we used quantitative RT-PCR gene expression studies in rat hepatoma cells as well as metabolic and gene expression profiling in primary hepatocytes of both wild-type and 5,10-methylenetetrahydrofolate reductase (MTHFR)-deficient mice. Anisotonic incubation caused coordinated adaptive changes in the expression of various genes involved in betaine metabolism, in particular of betaine homocysteine methyltransferase, dimethylglycine dehydrogenase, and sarcosine dehydrogenase. The expression of betaine-degrading enzymes was downregulated by cell shrinking and strongly induced by an increase in cell volume under hypotonic conditions. Metabolite concentrations in the culture system changed accordingly. Expression changes were mediated through tyrosine kinases, cyclic nucleotide-dependent protein kinases, and JNK-dependent signaling. Assessment of hepatic gene expression using a customized microarray chip showed that hepatic betaine depletion in MTHFR(-/-) mice was associated with alterations that were comparable to those induced by cell swelling in hepatocytes. In conclusion, the adaptation of hepatocytes to changes in cell volume involves the coordinated regulation of betaine synthesis and degradation and concomitant changes in intracellular osmolyte concentrations. The existence of such a well-orchestrated response underlines the importance of cell volume homeostasis for liver function and of methylamine osmolytes such as betaine as hepatic osmolytes.
- American journal of physiology. Gastrointestinal and liver physiology.Am J Physiol Gastrointest Liver Physiol.2013 May 1;304(9):G835-46. doi: 10.1152/ajpgi.00332.2012. Epub 2013 Feb 28.
- Betaine critically contributes to the control of hepatocellular hydration and provides protection of the liver from different kinds of stress. To investigate how the hepatocellular hydration state affects gene expression of enzymes involved in the metabolism of betaine and related organic osmolytes,
- PMID 23449672
Japanese Journal
- Over-expression in Escherichia coli, functional characterization and refolding of rat dimethylglycine dehydrogenase
- BRIZIO C.
- Protein Expr. Purif. 37, 434-442, 2004
- NAID 30018576160
Related Links
- The official name of this gene is “dimethylglycine dehydrogenase.” DMGDH is the gene's official symbol. The DMGDH gene is also known by other names, listed below. Read more about gene names and symbols on the About ...
- A number sign (#) is used with this entry because dimethylglycine dehydrogenase deficiency is caused by homozygous mutation in the DMGDH ...
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| リンク元 | 「ジメチルグリシン脱水素酵素」「ジメチルグリシンデヒドロゲナーゼ」 |
| 関連記事 | 「dehydrogenase」「dehydrogenases」 |