兒茶酚-O-甲基轉移酶

catechol-O-methyltransferase
命名
系統命名
縮寫
識別碼
EC編號	2.1.1.6
CAS號	9012-25-3
資料庫
IntEnz	IntEnz瀏覽
BRENDA（英語：BRENDA）	BRENDA入口
ExPASy（英語：ExPASy）	NiceZyme瀏覽
KEGG	KEGG入口
MetaCyc（英語：MetaCyc）	代謝路徑
PRIAM（英語：PRIAM_enzyme-specific_profiles）	概述
PDB	RCSB PDB PDBj PDBe PDBsum
基因本體	AmiGO / EGO
搜索
PMC	相關文獻
PubMed	相關文獻

兒茶酚-O-甲基轉移酶
Catechol-O-methyltransferase
兒茶酚-O-甲基轉移酶; Catechol-O-methyltransferase
	COMT和3,5-dinitrocatechol(深藍)以及S-腺苷甲硫氨酸(黃)結合。來自PDB 3BWM.
有效結構
PDB	直系同源檢索：PDBe, RCSB
PDB查詢代碼列表
	3A7E, 3BWM, 3BWY, 4PYI, 4PYJ, 4PYK, 4XUC, 4XUD, 4XUE
標識
代號	COMT; HEL-S-98n
擴展標識	遺傳學：116790 鼠基因：88470 同源基因：30982 ChEMBL: 2023 GeneCards: COMT Gene
EC編號	2.1.1.6
基因本體論描述
分子功能	· magnesium ion binding; · protein binding; · O-methyltransferase activity; · catechol O-methyltransferase activity;
細胞成分	· mitochondrion; · cytosol; · plasma membrane; · membrane; · integral component of membrane; · axon; · dendritic spine; · cell body; · postsynaptic membrane; · extracellular exosome;
生物過程	· 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表達模式
	更多表達數據
直系同源體
物種	人類
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查詢	[1]
	閱; 論; 編;

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葉斯·阿克塞爾羅德發現^[4]。

功能

兒茶酚-O-甲基轉移酶參與了兒茶酚胺神經遞質（多巴胺、腎上腺素以及去甲腎上腺素）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-胺基酸脫羧酶（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（英語：DOPAC） → HVA（高香草酸）
去甲腎上腺素 → 去甲變腎上腺素
腎上腺素 → 變腎上腺素
Dihydroxyphenylethylene glycol (DOPEG） → Methoxyhydroxyphenylglycol（英語：Methoxyhydroxyphenylglycol）（MOPEG）
3,4-Dihydroxymandelic acid (DOMA) → Vanillylmandelic acid（英語：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

COMT是編碼這個酶的基因的名字。名字中的O意指氧，不是ortho（英語：arene substitution patterns）。

COMT抑制劑

COMT抑制劑包括托卡朋（英語：tolcapone）以及恩他卡朋，常被用於治療帕金森氏症^[9]。

參見

額外圖片

參考資料

^ 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. 請檢查|date=中的日期值 (幫助)
^ 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.

深入閱讀

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

醫學主題詞表（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. 請檢查|date=中的日期值 (幫助)

[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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閱論編酶
活性	活性位點結合位點催化三聯體負氧離子洞酶催化混雜（英語：Enzyme promiscuity）催化最適酶（英語：Catalytically perfect enzyme）輔因子輔酶酶促反應
調節	別構調節協同性（英語：Cooperativity）酶抑制劑酶激活劑
分類	EC編號蛋白質超家族蛋白質家族酶列表
動力學	酶動力學伊迪-霍夫斯蒂圖（英語：Eadie–Hofstee diagram）哈尼斯-伍爾夫圖（英語：Hanes–Woolf plot）雙倒數圖米氏動力學
類型	EC1 氧化還原酶（列表（英語：List of EC numbers (EC 1)）） EC2 轉移酶（列表（英語：List of EC numbers (EC 2)）） EC3 水解酶（列表（英語：List of EC numbers (EC 3)）） EC4 裂合酶（列表（英語：List of EC numbers (EC 4)）） EC5 異構酶（列表（英語：List of EC numbers (EC 5)）） EC6 連接酶（列表（英語：List of EC numbers (EC 6)）） EC7 移位酶（英語：Translocase）（列表（英語：List of EC numbers (EC 7)））