硫嘌呤甲基转移酶
| 硫嘌呤甲基转移酶 | |||||||||||||
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 蛋白质资料库渲染的2bzg结构 | |||||||||||||
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| 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 | ||||||||||||
| RNA表达模式 | |||||||||||||
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| 更多表达数据 | |||||||||||||
| 直系同源体 | |||||||||||||
| 物种 | 人类 | 小鼠 | |||||||||||
| Entrez | 7172 | 22017 | |||||||||||
| Ensembl | ENSG00000137364 | ENSMUSG00000021376 | |||||||||||
| UniProt | P51580 | O55060 | |||||||||||
| mRNA序列 | NM_000367.2 | NM_016785.2 | |||||||||||
| 蛋白序列 | NP_000358.1 | NP_058065.2 | |||||||||||
| 基因位置 |
Chr 6: 18.13 – 18.16 Mb |
Chr 13: 47.12 – 47.14 Mb | |||||||||||
| PubMed查询 | [1] | [2] | |||||||||||
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]
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]
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）.
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