Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, Ohio, USA.
Department of Pharmacology, College of Pharmacy, University of Kufa, Najaf.
Pharmacogenet Genomics. 2019 Jul;29(5):99-105. doi: 10.1097/FPC.0000000000000371.
Phenylephrine and salbutamol are drugs that are used widely to treat diseases/disorders, such as nasal congestion, hypotension, and asthma, in individuals of different age groups. Human cytosolic sulfotransferase (SULT) SULT1A3 has been shown to be critically involved in the metabolism of these therapeutic agents. This study was carried out to investigate the effects of single nucleotide polymorphisms of human SULT1A3 and SULT1A4 genes on the sulfation of phenylephrine and salbutamol by SULT1A3 allozymes.
Wild-type and SULT1A3 allozymes, prepared previously by site-directed mutagenesis in conjunction with bacterial expression and affinity purification, were analyzed for sulfating activity using an established assay procedure.
Purified SULT1A3 allozymes, in comparison with the wild-type enzyme, showed differential sulfating activities toward phenylephrine and salbutamol. Kinetic studies showed further significant variations in their substrate-binding affinity and catalytic activity toward phenylephrine and salbutamol.
The results obtained showed clearly the differential enzymatic characteristics of SULT1A3 allozymes in mediating the sulfation of phenylephrine and salbutamol. This information may contribute toward a better understanding of the pharmacokinetics of these two drugs in individuals with distinct SULT1A3 and/or SULT1A4 genotypes.
苯肾上腺素和沙丁胺醇是广泛用于治疗不同年龄组个体的疾病/病症的药物，如鼻塞、低血压和哮喘。人细胞溶质磺基转移酶（SULT）SULT1A3 已被证明在这些治疗药物的代谢中起着至关重要的作用。本研究旨在探讨人 SULT1A3 和 SULT1A4 基因的单核苷酸多态性对 SULT1A3 同种型磺化苯肾上腺素和沙丁胺醇的影响。
通过定点诱变与细菌表达和亲和纯化相结合预先制备的野生型和 SULT1A3 同种型，使用建立的测定程序分析磺化活性。
与野生型酶相比，纯化的 SULT1A3 同种型对苯肾上腺素和沙丁胺醇表现出不同的磺化活性。动力学研究进一步表明，它们对苯肾上腺素和沙丁胺醇的底物结合亲和力和催化活性存在显著差异。
所得结果清楚地表明 SULT1A3 同种型在介导苯肾上腺素和沙丁胺醇磺化方面的酶学特征不同。这些信息可能有助于更好地了解具有不同 SULT1A3 和/或 SULT1A4 基因型的个体中这两种药物的药代动力学。
