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Enzyme Kinetics of PAPS-Sulfotransferase

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Enzyme Kinetics in Drug Metabolism

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2342))

Abstract

The cytosolic sulfotransferase (SULT) enzymes are found in human liver, kidney, intestine, and other tissues. These enzymes catalyze the transfer of the –SO3 group from 3′-phospho-adenosyl-5′-phosphosulfate (PAPS) to a nucleophilic hydroxyl or amine group in a drug substrate. SULTs are stable as dimers, with a highly conserved dimerization domain near the C-terminus of the protein. Crystal structures have revealed flexible loop regions in the native proteins, one of which, located near the dimerization domain, is thought to form a gate that changes position once PAPS is bound to the PAPS-binding site and modulates substrate access and enzyme properties. There is also evidence that oxidation and reduction of certain cysteine residues reversibly regulate the binding of the substrate and PAPS or PAP to the enzyme thus modulating sulfonation. Because SULT enzymes have two substrates, the drug and PAPS, it is common to report apparent kinetic constants with either the drug or the PAPS varied while the other is kept at a constant concentration. The kinetics of product formation can follow classic Michaelis-Menten kinetics, typically over a narrow range of substrate concentrations. Over a wide range of substrate concentrations, it is common to observe partial or complete substrate inhibition with SULT enzymes. This chapter describes the function, tissue distribution, structural features, and properties of the human SULT enzymes and presents examples of enzyme kinetics with different substrates.

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Author information

Authors and Affiliations

  1. Department of Medicinal Chemistry, University of Florida, Gainesville, FL, USA

    Margaret O. James

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  1. Margaret O. James
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Correspondence to Margaret O. James .

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Editors and Affiliations

  1. Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA

    Swati Nagar

  2. Translational Medicine, Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA

    Upendra A. Argikar

  3. Independent, Harleysville, PA, USA

    Donald Tweedie

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James, M.O. (2021). Enzyme Kinetics of PAPS-Sulfotransferase. In: Nagar, S., Argikar, U.A., Tweedie, D. (eds) Enzyme Kinetics in Drug Metabolism. Methods in Molecular Biology, vol 2342. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1554-6_11

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  • DOI: https://doi.org/10.1007/978-1-0716-1554-6_11

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1553-9

  • Online ISBN: 978-1-0716-1554-6

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