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Impact of SULT1A3/SULT1A4 genetic polymorphisms on the sulfation of phenylephrine and salbutamol by human SULT1A3 allozymes

Bairam, Ahsan F.a,b; Rasool, Mohammed I.a,c; Alherz, Fatemah A.a; Abunnaja, Maryam S.a; El Daibani, Amal A.a; Gohal, Saud A.a; Alatwi, Eid S.a; Kurogi, Katsuhisaa,d; Liu, Ming-Cheha

Pharmacogenetics and Genomics: July 2019 - Volume 29 - Issue 5 - p 99–105
doi: 10.1097/FPC.0000000000000371
ORIGINAL ARTICLES
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Objectives 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.

Materials and methods 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.

Results 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.

Conclusion 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.

aDepartment of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, Ohio, USA

bDepartment of Pharmacology, College of Pharmacy, University of Kufa, Najaf

cDepartment of Pharmacology, College of Pharmacy, University of Karbala, Karbala, Iraq

dBiochemistry and Applied Biosciences, University of Miyazaki, Miyazaki, Japan

Correspondence to Ming-Cheh Liu, PhD, Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA Tel: +1 419 383 1918; fax: +1 419 383 1909; e-mail: ming.liu@utoledo.edu

Received June 13, 2018

Accepted December 24, 2018

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