儿茶酚-O-甲基转移酶

catechol-O-methyltransferase
命名
系统命名
缩写
识别码
EC编号	2.1.1.6
CAS号	9012-25-3
数据库
IntEnz	IntEnz浏览
BRENDA（英语：BRENDA）	BRENDA入口
ExPASy（英语：ExPASy）	NiceZyme浏览
KEGG	KEGG入口
MetaCyc（英语：MetaCyc）	代谢路径
PRIAM（英语：PRIAM_enzyme-specific_profiles）	概述
PDB	RCSB PDB PDBj PDBe PDBsum
基因本体	AmiGO / EGO
搜索
PMC	相关文献
PubMed	相关文献

儿茶酚-O-甲基转移酶
Catechol-O-methyltransferase
儿茶酚-O-甲基转移酶; Catechol-O-methyltransferase
	COMT和3,5-dinitrocatechol(深蓝)以及S-腺苷甲硫氨酸(黄)结合。来自PDB 3BWM.
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	3A7E, 3BWM, 3BWY, 4PYI, 4PYJ, 4PYK, 4XUC, 4XUD, 4XUE
标识
代号	COMT; HEL-S-98n
扩展标识	遗传学：116790 鼠基因：88470 同源基因：30982 ChEMBL: 2023 GeneCards: COMT Gene
EC编号	2.1.1.6
基因本体论描述
分子功能	· magnesium ion binding; · protein binding; · O-methyltransferase activity; · catechol O-methyltransferase activity;
细胞成分	· mitochondrion; · cytosol; · plasma membrane; · membrane; · integral component of membrane; · axon; · dendritic spine; · cell body; · postsynaptic membrane; · extracellular exosome;
生物过程	· xenobiotic metabolic process; · synaptic transmission; · female pregnancy; · learning; · short-term memory; · estrogen metabolic process; · response to organic cyclic compound; · cellular response to phosphate starvation; · methylation; · response to lipopolysaccharide; · developmental process; · negative regulation of renal sodium excretion; · neurotransmitter catabolic process; · neurotransmitter biosynthetic process; · dopamine catabolic process; · response to drug; · small molecule metabolic process; · negative regulation of dopamine metabolic process; · response to pain; · multicellular organismal reproductive process; · negative regulation of smooth muscle cell proliferation; · positive regulation of homocysteine metabolic process; · regulation of sensory perception of pain;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体
物种	人类
Entrez	1312
Ensembl	ENSG00000093010
UniProt	P21964
mRNA序列	NM_000754
蛋白序列	NP_000745
基因位置	Chr 22:; 19.94 – 19.97 Mb
PubMed查询	[1]
	查; 论; 编;

儿茶酚-O-甲基转移酶（COMT; EC 2.1.1.6）是分解儿茶酚胺（如多巴胺、肾上腺素和去甲肾上腺素）的几种酶之一。在人体，儿茶酚-O-甲基转移酶由COMT基因编码^[2]。鉴于在一些疾病中儿茶酚胺的调节受损，数种药物以COMT为标靶，调整其活性来控制儿茶酚胺的浓度^[3]。

COMT在1957年由生物化学家朱利叶斯·阿克塞尔罗德发现^[4]。

功能

儿茶酚-O-甲基转移酶参与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，它在儿茶酚胺上加入由 S-腺苷甲硫氨酸（SAM）给予的甲基。具有邻苯二酚结构的物质都是COMT的基质，如儿茶酚雌激素以及含有邻苯二酚的黄酮类化合物。 L-多巴，儿茶酚胺的前驱物，是COMT重要的基质。COMT抑制剂如恩他卡朋，使L-多巴不被COMT分解为3-O-甲基多巴（3-OMD），剩下芳香族L-氨基酸脱羧酶（DACC）途径，同时增加其半衰期^[5]^[6]。延长L-多巴药物时效。

由COMT催化的反应包含:

多巴胺 → 3-Methoxytyramine
DOPAC（英语：DOPAC） → HVA（高香草酸）
去甲肾上腺素 → 去甲变肾上腺素
肾上腺素 → 变肾上腺素
Dihydroxyphenylethylene glycol (DOPEG） → Methoxyhydroxyphenylglycol（英语：Methoxyhydroxyphenylglycol）（MOPEG）
3,4-Dihydroxymandelic acid (DOMA) → Vanillylmandelic acid（英语：Vanillylmandelic acid）（VMA）

在脑部，依赖COMT的多巴胺降解于低多巴胺转运体（DAT）表现的区域特别重要，如前额叶皮质^[7]^[8]。

命名

COMT是编码这个酶的基因的名字。名字中的O意指氧，不是ortho（英语：arene substitution patterns）。

COMT抑制剂

COMT抑制剂包括托卡朋（英语：tolcapone）以及恩他卡朋，常被用于治疗帕金森氏症^[9]。

参见

额外图片

参考资料

^ 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. 请检查|date=中的日期值 (帮助)
^ 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.

深入阅读

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.

外部链接

医学主题词表（MeSH）：Catechol+O-Methyltransferase

[Rang&Dale6th-11-4-1] 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.

[pmid1572656-2] 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.

[pmid11873938-3] Tai CH, Wu RM. Catechol-O-methyltransferase and Parkinson's disease. Acta Med. Okayama. February 2002, 56 (1): 1–6. PMID 11873938.

[pmid13467217-4] 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.

[PD-5] 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. 请检查|date=中的日期值 (帮助)

[pmidhttp://www.ncbi.nlm.nih.gov/pubmed/9591519-6] Goetz CG. Influence of COMT inhibition on levodopa pharmacology and therapy.. Neurology. 1998, 50 (5 Suppl 5): S26–30. PMID 9591519.

[pmid12535946-7] 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.

[8] 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.

[pmid17894650-9] 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.

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