硫嘌呤甲基转移酶

硫嘌呤甲基转移酶
硫嘌呤甲基转移酶
	蛋白质资料库渲染的2bzg结构
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	2BZG, 2H11
标识
代号	TPMT; []
扩展标识	遗传学：187680 鼠基因：98812 同源基因：313 ChEMBL: 2500 GeneCards: TPMT Gene
EC编号	2.1.1.67
基因本体论描述
分子功能	· thiopurine S-methyltransferase activity; · methyltransferase activity; · transferase activity;
细胞成分	· cytoplasm; · cytosol;
生物过程	· nucleobase-containing compound metabolic process; · xenobiotic metabolic process; · methylation; · small molecule metabolic process;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体
物种	人类
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查询	[1]
	查; 论; 编;

硫嘌呤甲基转移酶（英语：Thiopurine methyltransferase或Thiopurine S-methyltransferase，EC 2.1.1.67），又称巯基嘌呤甲基转移酶或巯嘌呤甲基转移酶，简称TPMT，是一种催化硫嘌呤类化合物甲基化的酶。硫嘌呤类药物常用于癌症化学疗法及免疫抑制疗法，因而TPMT的活性会影响使用这类药物时不同患者对药物的敏感性和毒性反应。^[1]^[2]

TPMT在18q染色体上有一个伪基因。^[1]^[3]

药理学

TPMT是硫嘌呤类药物（如硫唑嘌呤、巯嘌呤和硫鸟嘌呤）的代谢中最主要的酶之一，起到的作用是在这类化合物的硫原子上增加一个甲基；这个过程中提供甲基的是S-腺苷甲硫氨酸，后者同时被转化成S-腺苷-L-高半胱氨酸。^[4] TPMT基因的缺陷会让人体无法将这类药物灭活，未代谢的药物因此在体内大量累积，从而引起严重甚至致命的骨髓抑制，表现为贫血、血小板减少症（导致出血）和白细胞减少症（导致感染）等。^[2]^[5]

临床意义

研究显示，临床上大约5%的硫嘌呤类药物疗法由于毒性原因而终止。^[6] 一般来说，在使用硫嘌呤类药物前及治疗过程中会多次测量病人的TPMT酶活性，以防止TPMT不活跃者（占总人口约10%）及TPMT无活性者（占总人口约0.3%）在使用这类药物后产生的严重骨髓毒性。^[4] 近年来也开始采用基因测试，相对于前者优点在于测试不需要反复进行。^[7]

不同人种的TPMT基因突变分布情况有着极大的不同。^[8]

参考资料

^ ^1.0 ^1.1 Entrez Gene: TPMT thiopurine S-methyltransferase. 美国国家生物技术信息中心. [2012-07-02]. （原始内容存档于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. （原始内容存档于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]. （原始内容存档于2021-04-14）.

[entrez-1] 1.0 ^1.1 Entrez Gene: TPMT thiopurine S-methyltransferase. 美国国家生物技术信息中心. [2012-07-02]. （原始内容存档于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. （原始内容存档于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]. （原始内容存档于2021-04-14）.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]