Sulfation of catecholamines and serotonin by SULT1A3 allozymes.
Sulfation of catecholamines and serotonin by SULT1A3 allozymes.
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DOI：
10.1016/j.bcp.2018.03.005
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发表时间：
2018-05
影响因子：
5.8
通讯作者：
Liu MC
中科院分区：
文献类型：
--
作者：
Bairam AF;Rasool MI;Alherz FA;Abunnaja MS;El Daibani AA;Gohal SA;Kurogi K;Sakakibara Y;Suiko M;Liu MC
先前的研究已经证明磺基结合参与儿茶酚胺和血清素的代谢。本研究旨在阐明人类SULT1A3和SULT1A4基因的单核苷酸多态性（SNP）对SULT1A3同种酶硫酸化多巴胺、肾上腺素、去甲肾上腺素和血清素的酶学特性的影响。对不同 SULT1A3 和 SULT1A4 基因型进行全面搜索后，鉴定出 SULT1A3/SULT1A4 的 12 个非同义（错义）编码 SNP (cSNP)。通过定点诱变生成包装在 pGEX-2T 载体中的编码相应 SULT1A3 同种酶的 cDNA。 SULT1A3 同种酶被表达并纯化。纯化的 SULT1A3 同种酶对儿茶酚胺和血清素表现出不同的硫酸化活性。动力学分析表明 SULT1A3 同种酶的底物亲和力和催化效率存在差异。总的来说，这些发现提供了与具有不同 SULT1A3/SULT1A4 基因型的个体中多巴胺、肾上腺素、去甲肾上腺素和血清素通过磺基结合的差异代谢相关的有用信息。
Previous studies have demonstrated the involvement of sulfoconjugation in the metabolism of catecholamines and serotonin. The current study aimed to clarify the effects of single nucleotide polymorphisms (SNPs) of human SULT1A3 and SULT1A4 genes on the enzymatic characteristics of the sulfation of dopamine, epinephrine, norepinephrine and serotonin by SULT1A3 allozymes. Following a comprehensive search of different SULT1A3 and SULT1A4 genotypes, twelve non-synonymous (missense) coding SNPs (cSNPs) of SULT1A3/SULT1A4 were identified. cDNAs encoding the corresponding SULT1A3 allozymes, packaged in pGEX-2T vector were generated by site-directed mutagenesis. SULT1A3 allozymes were expressed, and purified. Purified SULT1A3 allozymes exhibited differential sulfating activity toward catecholamines and serotonin. Kinetic analyses demonstrated differences in both substrate affinity and catalytic efficiency of the SULT1A3 allozymes. Collectively, these findings provide useful information relevant to the differential metabolism of dopamine, epinephrine, norepinephrine and serotonin through sulfoconjugation in individuals having different SULT1A3/SULT1A4 genotypes.
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