儿茶酚-O-甲基转移酶
| catechol-O-methyltransferase | |||||||
|---|---|---|---|---|---|---|---|
| |||||||
| 识别码 | |||||||
| EC編號 | 2.1.1.6 | ||||||
| CAS号 | 9012-25-3 | ||||||
| 数据库 | |||||||
| IntEnz | IntEnz浏览 | ||||||
| BRENDA | BRENDA入口 | ||||||
| ExPASy | NiceZyme浏览 | ||||||
| KEGG | KEGG入口 | ||||||
| MetaCyc | 代谢路径 | ||||||
| PRIAM | 概述 | ||||||
| PDB | RCSB PDB PDBj PDBe PDBsum | ||||||
| 基因本体 | AmiGO / EGO | ||||||
| |||||||
兒茶酚-O-甲基轉移酶（COMT; EC 2.1.1.6）是分解兒茶酚胺（如多巴胺、腎上腺素和去甲腎上腺素）的幾種酶之一。在人體，兒茶酚-O-甲基轉移酶由COMT基因編碼[2]。鑒於在一些疾病中兒茶酚胺的調節受損，數種藥物以COMT為標靶，調整其活性來控制兒茶酚胺的濃度[3]。
COMT在1957年由生物化學家 朱利叶斯·阿克塞尔罗德發現[4]。
功能
[编辑]兒茶酚-O-甲基轉移酶參與了儿茶酚胺神经递质（多巴胺、肾上腺素以及去甲肾上腺素）的去活性化，它在兒茶酚胺上加入由 S-腺苷甲硫氨酸（SAM）給予的甲基。具有鄰苯二酚結構的物質都是COMT的基質，如兒茶酚雌激素以及含有鄰苯二酚的黃酮類化合物。 L-多巴，兒茶酚胺的前驅物，是COMT重要的基質。COMT抑制劑如恩他卡朋，使L-多巴不被COMT分解為3-O-甲基多巴（3-OMD），剩下芳香族L-氨基酸脫羧酶（DACC）途徑，同時增加其半衰期[5][6]。延長L-多巴藥物時效。
由COMT催化的反應包含:
- 多巴胺 → 3-Methoxytyramine
- DOPAC → HVA（高香草酸）
- 去甲肾上腺素 → 去甲變腎上腺素
- 肾上腺素 → 變腎上腺素
- Dihydroxyphenylethylene glycol (DOPEG） → Methoxyhydroxyphenylglycol（MOPEG）
- 3,4-Dihydroxymandelic acid (DOMA) → Vanillylmandelic acid（VMA）
在腦部，依賴COMT的多巴胺降解於低多巴胺轉運體（DAT）表現的區域特別重要，如前額葉皮質[7][8]。
命名
[编辑]COMT是編碼這個酶的基因的名字。名字中的O意指氧，不是ortho。
COMT抑制劑
[编辑]COMT抑制劑包括托卡朋以及恩他卡朋，常被用於治療帕金森氏症[9]。
參見
[编辑]額外圖片
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參考資料
[编辑]- ^ Figure 11-4 in: Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. 2007. ISBN 0-443-06911-5.
- ^ Grossman MH, Emanuel BS, Budarf ML. Chromosomal mapping of the human catechol-O-methyltransferase gene to 22q11.1-q11.2. Genomics. April 1992, 12 (4): 822–5. PMID 1572656. doi:10.1016/0888-7543(92)90316-K.
- ^ Tai CH, Wu RM. Catechol-O-methyltransferase and Parkinson's disease. Acta Med. Okayama. February 2002, 56 (1): 1–6. PMID 11873938.
- ^ Axelrod J. O-Methylation of Epinephrine and Other Catechols in vitro and in vivo. Science. August 1957, 126 (3270): 400–1. PMID 13467217. doi:10.1126/science.126.3270.400.
- ^ H. M. Ruottinen & U. K. Rinne. COMT inhibition in the treatment of Parkinson's disease. Journal of neurology. 1998 November, 245 (11 Suppl 3): P25–P34. PMID 9808337.
- ^ Goetz CG. Influence of COMT inhibition on levodopa pharmacology and therapy.. Neurology. 1998, 50 (5 Suppl 5): S26–30. PMID 9591519.
- ^ Matsumoto M, Weickert CS, Akil M, Lipska BK, Hyde TM, Herman MM, Kleinman JE, Weinberger DR. Catechol O-methyltransferase mRNA expression in human and rat brain: evidence for a role in cortical neuronal function. Neuroscience. 2003, 116 (1): 127–37. PMID 12535946. doi:10.1016/S0306-4522(02)00556-0.
- ^ Karoum F, Chrapusta SJ, Egan MF. 3-Methoxytyramine is the Major Metabolite of Released Dopamine in the Rat Frontal Cortex: Reassessment of the Effects of Antipsychotics on the Dynamics of Dopamine Release and Metabolism in the Frontal Cortex, Nucleus Accumbens, and Striatum by a Simple T. Journal of Neurochemistry. 2002, 63 (3): 972–9. PMID 7914228. doi:10.1046/j.1471-4159.1994.63030972.x.
- ^ Bonifácio MJ, Palma PN, Almeida L, Soares-da-Silva P. Catechol-O-methyltransferase and its inhibitors in Parkinson's disease. CNS Drug Rev. 2007, 13 (3): 352–79. PMID 17894650. doi:10.1111/j.1527-3458.2007.00020.x.
深入閱讀
[编辑]- Wichers M, Aguilera M, Kenis G, Krabbendam L, Myin-Germeys I, Jacobs N, Peeters F, Derom C, Vlietinck R, Mengelers R, Delespaul P, van Os J. The Catechol-O-Methyl Transferase Val158Met Polymorphism and Experience of Reward in the Flow of Daily Life. Neuropsychopharmacology. 2008, 33 ((2008) 33, 3030–3036): 3030–6. PMID 17687265. doi:10.1038/sj.npp.1301520.http://www.nature.com/npp/journal/v33/n13/full/1301520a.html
- Trendelenburg U. The interaction of transport mechanisms and intracellular enzymes in metabolizing systems. J. Neural Transm. Suppl. 1991, 32: 3–18. PMID 2089098. doi:10.1007/978-3-7091-9113-2_1.
- Tai CH, Wu RM. Catechol-O-methyltransferase and Parkinson's disease. Acta Med. Okayama. 2002, 56 (1): 1–6. PMID 11873938.
- Zhu BT. On the mechanism of homocysteine pathophysiology and pathogenesis: a unifying hypothesis. Histol. Histopathol. 2003, 17 (4): 1283–91. PMID 12371153.
- Oroszi G, Goldman D. Alcoholism: genes and mechanisms. Pharmacogenomics. 2005, 5 (8): 1037–48. PMID 15584875. doi:10.1517/14622416.5.8.1037.
- Fan JB, Zhang CS, Gu NF, Li XW, Sun WW, Wang HY, Feng GY, St Clair D, He L. Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biol. Psychiatry. 2005, 57 (2): 139–44. PMID 15652872. doi:10.1016/j.biopsych.2004.10.018.
- Tunbridge EM, Harrison PJ, Weinberger DR. Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biol. Psychiatry. 2006, 60 (2): 141–51. PMID 16476412. doi:10.1016/j.biopsych.2005.10.024.
- Diaz-Asper CM, Weinberger DR, Goldberg TE. Catechol-O-methyltransferase polymorphisms and some implications for cognitive therapeutics. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics. 2006, 3 (1): 97–105. PMC 3593358
. PMID 16490416. doi:10.1016/j.nurx.2005.12.010. - Craddock N, Owen MJ, O'Donovan MC. The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons. Mol. Psychiatry. 2006, 11 (5): 446–58. PMID 16505837. doi:10.1038/sj.mp.4001808.
- Frank MJ, Moustafa AA, Haughey HM, Curran T, Hutchison KE. Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning. Proc Natl Acad Sci USA. 2007, 104 (41): 16311–6. PMC 2042203 . PMID 17913879. doi:10.1073/pnas.0706111104.
外部連結
[编辑]
维基共享资源上的相关多媒体资源：儿茶酚-O-甲基转移酶
