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
	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
	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[編輯]

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[編輯]

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[編輯]

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[編輯]

額外圖片[編輯]

參考資料[編輯]

^ 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[編輯]

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[編輯]

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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]