硫嘌呤甲基轉移酶

硫嘌呤甲基轉移酶
硫嘌呤甲基轉移酶
	蛋白質資料庫渲染的2bzg結構
有效結構
PDB	直系同源檢索：PDBe, RCSB
PDB查詢代碼列表
	2BZG, 2H11
標識
代號	TPMT; []
擴展標識	遺傳學：187680 鼠基因：98812 同源基因：313 ChEMBL: 2500 GeneCards: TPMT Gene
EC編號	2.1.1.67
基因本體論描述
分子功能	· thiopurine S-methyltransferase activity; · methyltransferase activity; · transferase activity;
細胞成分	· cytoplasm; · cytosol;
生物過程	· nucleobase-containing compound metabolic process; · xenobiotic metabolic process; · methylation; · small molecule metabolic process;
	Sources: Amigo / QuickGO
RNA表達模式
	更多表達數據
直系同源體
物種	人類
Entrez	7172
Ensembl	ENSG00000137364
UniProt	P51580
mRNA序列	NM_000367.2
蛋白序列	NP_000358.1
基因位置	Chr 6:; 18.13 – 18.16 Mb
PubMed查詢	[1]
	閱; 論; 編;

硫嘌呤甲基轉移酶（英語：Thiopurine methyltransferase或Thiopurine S-methyltransferase，EC 2.1.1.67），又稱巰基嘌呤甲基轉移酶或巰嘌呤甲基轉移酶，簡稱TPMT，是一種催化硫嘌呤類化合物甲基化的酶。硫嘌呤類藥物常用於癌症化學療法及免疫抑制療法，因而TPMT的活性會影響使用這類藥物時不同患者對藥物的敏感性和毒性反應。^[1]^[2]

TPMT在18q染色體上有一個偽基因。^[1]^[3]

藥理學

TPMT是硫嘌呤類藥物（如硫唑嘌呤、巰嘌呤和硫鳥嘌呤）的代謝中最主要的酶之一，起到的作用是在這類化合物的硫原子上增加一個甲基；這個過程中提供甲基的是S-腺苷甲硫氨酸，後者同時被轉化成S-腺苷-L-高半胱氨酸。^[4] TPMT基因的缺陷會讓人體無法將這類藥物滅活，未代謝的藥物因此在體內大量累積，從而引起嚴重甚至致命的骨髓抑制，表現為貧血、血小板減少症（導致出血）和白細胞減少症（導致感染）等。^[2]^[5]

臨床意義

研究顯示，臨床上大約5%的硫嘌呤類藥物療法由於毒性原因而終止。^[6] 一般來說，在使用硫嘌呤類藥物前及治療過程中會多次測量病人的TPMT酶活性，以防止TPMT不活躍者（佔總人口約10%）及TPMT無活性者（佔總人口約0.3%）在使用這類藥物後產生的嚴重骨髓毒性。^[4] 近年來也開始採用基因測試，相對於前者優點在於測試不需要反覆進行。^[7]

不同人種的TPMT基因突變分佈情況有着極大的不同。^[8]

參考資料

^ ^1.0 ^1.1 Entrez Gene: TPMT thiopurine S-methyltransferase. 美國國家生物技術信息中心. [2012-07-02]. （原始內容存檔於2010-03-08）.
^ ^2.0 ^2.1 Yates, C. R.; Krynetski, E. Y.; Loennechen, T.; Fessing, M. Y.; Tai, H. L.; Pui, C. H.; Relling, M. V.; Evans, W. E. Molecular diagnosis of thiopurine S-methyltransferase deficiency: Genetic basis for azathioprine and mercaptopurine intolerance. Annals of internal medicine. 1997, 126 (8): 608–614. PMID 9103127.
^ Lee, D.; Szumlanski, C.; Houtman, J.; Honchel, R.; Rojas, K.; Overhauser, J.; Wieben, E. D.; Weinshilboum, R. M. Thiopurine methyltransferase pharmacogenetics. Cloning of human liver cDNA and a processed pseudogene on human chromosome 18q21.1. Drug metabolism and disposition: the biological fate of chemicals. 1995, 23 (3): 398–405. PMID 7628307.
^ ^4.0 ^4.1 Weinshilboum, R. M.; Sladek, S. L. Mercaptopurine pharmacogenetics: Monogenic inheritance of erythrocyte thiopurine methyltransferase activity. American journal of human genetics. 1980, 32 (5): 651–662. PMC 1686086 . PMID 7191632.
^ Fujita K, Sasaki Y. Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy. Curr. Drug Metab. August 2007, 8 (6): 554–62. PMID 17691917. doi:10.2174/138920007781368890. （原始內容存檔於2013-01-12）.
^ Reuther LO, Vainer B, Sonne J, Larsen NE. Thiopurine methyltransferase (TPMT) genotype distribution in azathioprine-tolerant and -intolerant patients with various disorders. The impact of TPMT genotyping in predicting toxicity. Eur. J. Clin. Pharmacol. January 2004, 59 (11): 797–801. PMID 14634700. doi:10.1007/s00228-003-0698-8.
^ Payne, K.; Newman, W.; Fargher, E.; Tricker, K.; Bruce, I. N.; Ollier, W. E. R. TPMT testing in rheumatology: Any better than routine monitoring?. Rheumatology. 2007, 46 (5): 727–729. PMID 17255139. doi:10.1093/rheumatology/kel427.
^ Genome Bioinformatics Group, Center for Biomolecular Science and Engineering. Human Gene TPMT (uc003ncm.1). UCSC Genome Browser. University of California Santa Cruz. [2008-07-25]. （原始內容存檔於2021-04-14）.

[entrez-1] 1.0 ^1.1 Entrez Gene: TPMT thiopurine S-methyltransferase. 美國國家生物技術信息中心. [2012-07-02]. （原始內容存檔於2010-03-08）.

[duo-2] 2.0 ^2.1 Yates, C. R.; Krynetski, E. Y.; Loennechen, T.; Fessing, M. Y.; Tai, H. L.; Pui, C. H.; Relling, M. V.; Evans, W. E. Molecular diagnosis of thiopurine S-methyltransferase deficiency: Genetic basis for azathioprine and mercaptopurine intolerance. Annals of internal medicine. 1997, 126 (8): 608–614. PMID 9103127.

[3] Lee, D.; Szumlanski, C.; Houtman, J.; Honchel, R.; Rojas, K.; Overhauser, J.; Wieben, E. D.; Weinshilboum, R. M. Thiopurine methyltransferase pharmacogenetics. Cloning of human liver cDNA and a processed pseudogene on human chromosome 18q21.1. Drug metabolism and disposition: the biological fate of chemicals. 1995, 23 (3): 398–405. PMID 7628307.

[xl-4] 4.0 ^4.1 Weinshilboum, R. M.; Sladek, S. L. Mercaptopurine pharmacogenetics: Monogenic inheritance of erythrocyte thiopurine methyltransferase activity. American journal of human genetics. 1980, 32 (5): 651–662. PMC 1686086 . PMID 7191632.

[pmid17691917-5] Fujita K, Sasaki Y. Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy. Curr. Drug Metab. August 2007, 8 (6): 554–62. PMID 17691917. doi:10.2174/138920007781368890. （原始內容存檔於2013-01-12）.

[6] Reuther LO, Vainer B, Sonne J, Larsen NE. Thiopurine methyltransferase (TPMT) genotype distribution in azathioprine-tolerant and -intolerant patients with various disorders. The impact of TPMT genotyping in predicting toxicity. Eur. J. Clin. Pharmacol. January 2004, 59 (11): 797–801. PMID 14634700. doi:10.1007/s00228-003-0698-8.

[7] Payne, K.; Newman, W.; Fargher, E.; Tricker, K.; Bruce, I. N.; Ollier, W. E. R. TPMT testing in rheumatology: Any better than routine monitoring?. Rheumatology. 2007, 46 (5): 727–729. PMID 17255139. doi:10.1093/rheumatology/kel427.

[urlHuman_Gene_TPMT_(uc003ncm.1)_Description_and_Page_Index-8] Genome Bioinformatics Group, Center for Biomolecular Science and Engineering. Human Gene TPMT (uc003ncm.1). UCSC Genome Browser. University of California Santa Cruz. [2008-07-25]. （原始內容存檔於2021-04-14）.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]