Abstract
The sulfotransferase (SULT) enzymes catalyze the formation of sulfate esters or sulfamates from substrates that contain hydroxy or amine groups, utilizing 3′-phosphoadenosyl-5′-phosphosulfate (PAPS) as the donor of the sulfonic group. The rate of product formation depends on the concentrations of PAPS and substrate as well as the sulfotransferase enzyme; thus, if PAPS is held constant while varying substrate concentration (or vice versa), the kinetic constants derived are apparent constants. When studied over a narrow range of substrate concentrations, classic Michaelis–Menten kinetics can be observed with many SULT enzymes and most substrates. Some SULT enzymes exhibit positive or negative cooperativity during conversion of substrate to product, and the kinetics fit the Hill plot. A characteristic feature of most sulfotransferase-catalyzed reactions is that, when studied over a wide range of substrate concentrations, the rate of product formation initially increases as substrate concentration increases, then decreases at high substrate concentrations, i.e., they exhibit substrate inhibition or partial substrate inhibition. This chapter gives an introduction to sulfotransferases, including a historical note, the nomenclature, a description of the function of SULTs with different types of substrates, presentation of examples of enzyme kinetics with SULTs, and a discussion of what is known about mechanisms of substrate inhibition in the sulfotransferases.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Williams RT (1959) Detoxication mechanisms The metabolism and detoxication of drugs, toxic substances and other organic compounds. Chapman and Hall, Ltd., London
Robbins PW, Lipmann F (1957) Isolation and identification of active sulfate. J Biol Chem 229(2):837–851
Falany CN (1997) Enzymology of human cytosolic sulfotransferases. FASEB J 11(4):206–216
Strott CA (2002) Sulfonation and molecular action. Endocr Rev 23(5):703–732
Miki Y, Nakata T, Suzuki T, Darnel AD, Moriya T, Kaneko C, Hidaka K, Shiotsu Y, Kusaka H, Sasano H (2002) Systemic distribution of steroid sulfatase and estrogen sulfotransferase in human adult and fetal tissues. J Clin Endocrinol Metab 87(12):5760–5768
Teubner W, Meinl W, Florian S, Kretzschmar M, Glatt H (2007) Identification and localization of soluble sulfotransferases in the human gastrointestinal tract. Biochem J 404(2):207–215. doi:10.1042/BJ20061431, BJ20061431 [pii]
Riches Z, Stanley EL, Bloomer JC, Coughtrie MW (2009) Quantitative evaluation of the expression and activity of five major sulfotransferases (SULTs) in human tissues: the SULT “pie”. Drug Metab Dispos 37(11):2255–2261. doi:10.1124/dmd.109.028399, dmd.109.028399 [pii]
Blanchard RL, Freimuth RR, Buck J, Weinshilboum RM, Coughtrie MW (2004) A proposed nomenclature system for the cytosolic sulfotransferase (SULT) superfamily. Pharmacogenetics 14(3):199–211
Alnouti Y, Klaassen CD (2006) Tissue distribution and ontogeny of sulfotransferase enzymes in mice. Toxicol Sci 93(2):242–255. doi:10.1093/toxsci/kfl050, kfl050 [pii]
Wang LQ, James MO (2006) Inhibition of sulfotransferases by xenobiotics. Curr Drug Metab 7(1):83–104
Negishi M, Pedersen LG, Petrotchenko E, Shevtsov S, Gorokhov A, Kakuta Y, Pedersen LC (2001) Structure and function of sulfotransferases. Arch Biochem Biophys 390(2):149–157. doi:10.1006/abbi.2001.2368, S0003-9861(01)92368-9 [pii]
Rohn KJ, Cook IT, Leyh TS, Kadlubar SA, Falany CN (2012) Potent inhibition of human sulfotransferase 1A1 by 17alpha-ethinylestradiol: role of 3′-phosphoadenosine 5′-phosphosulfate binding and structural rearrangements in regulating inhibition and activity. Drug Metab Dispos 40(8):1588–1595. doi:10.1124/dmd.112.045583, dmd.112.045583 [pii]
Gulcan HO, Duffel MW (2011) Substrate inhibition in human hydroxysteroid sulfotransferase SULT2A1: studies on the formation of catalytically non-productive enzyme complexes. Arch Biochem Biophys 507(2):232–240. doi:10.1016/j.abb.2010.12.027, S0003-9861(10)00524-2 [pii]
Chapman E, Best MD, Hanson SR, Wong CH (2004) Sulfotransferases: structure, mechanism, biological activity, inhibition, and synthetic utility. Angew Chem Int Ed Engl 43(27):3526–3548. doi:10.1002/anie.200300631
Duffel MW, Marshal AD, McPhie P, Sharma V, Jakoby WB (2001) Enzymatic aspects of the phenol (aryl) sulfotransferases. Drug Metab Rev 33(3–4):369–395. doi:10.1081/DMR-120001394
Gamage NU, Tsvetanov S, Duggleby RG, McManus ME, Martin JL (2005) The structure of human SULT1A1 crystallized with estradiol. An insight into active site plasticity and substrate inhibition with multi-ring substrates. J Biol Chem 280(50):41482–41486. doi:10.1074/jbc.M508289200, M508289200[pii]
Cook I, Wang T, Falany CN, Leyh TS (2012) A nucleotide-gated molecular pore selects sulfotransferase substrates. Biochemistry 51(28):5674–5683. doi:10.1021/bi300631g
Wu B (2011) Substrate inhibition kinetics in drug metabolism reactions. Drug Metab Rev 43(4):440–456. doi:10.3109/03602532.2011.615320
Zhang H, Varlamova O, Vargas FM, Falany CN, Leyh TS (1998) Sulfuryl transfer: the catalytic mechanism of human estrogen sulfotransferase. J Biol Chem 273(18):10888–10892
Klaassen CD, Boles JW (1997) Sulfation and sulfotransferases 5: the importance of 3′-phosphoadenosine 5′-phosphosulfate (PAPS) in the regulation of sulfation. FASEB J 11(6):404–418
De Santi C, Pietrabissa A, Spisni R, Mosca F, Pacifici GM (2000) Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum. Xenobiotica 30(6):609–617. doi:10.1080/004982500406435
Hirshey SJ, Falany CN (1990) Purification and characterization of rat liver minoxidil sulphotransferase. Biochem J 270(3):721–728
Vaidyanathan JB, Walle T (2002) Glucuronidation and sulfation of the tea flavonoid (-)-epicatechin by the human and rat enzymes. Drug Metab Dispos 30(8):897–903
Sacco JC, James MO (2005) Sulfonation of environmental chemicals and their metabolites in the polar bear (Ursus maritimus). Drug Metab Dispos 33(9):1341–1348. doi:10.1124/dmd.105.004648, dmd.105. 004648 [pii]
Tyapochkin E, Kumar VP, Cook PF, Chen G (2011) Reaction product affinity regulates activation of human sulfotransferase 1A1 PAP sulfation. Arch Biochem Biophys 506(2):137–141. doi:10.1016/j.abb.2010.11.018, S0003-9861(10)00491-1 [pii]
Sundaram RS, Szumlanski C, Otterness D, van Loon JA, Weinshilboum RM (1989) Human intestinal phenol sulfotransferase: assay conditions, activity levels and partial purification of the thermolabile form. Drug Metab Dispos 17(3):255–264
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
James, M.O. (2014). Enzyme Kinetics of Conjugating Enzymes: PAPS Sulfotransferase. In: Nagar, S., Argikar, U., Tweedie, D. (eds) Enzyme Kinetics in Drug Metabolism. Methods in Molecular Biology, vol 1113. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-758-7_10
Download citation
DOI: https://doi.org/10.1007/978-1-62703-758-7_10
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-757-0
Online ISBN: 978-1-62703-758-7
eBook Packages: Springer Protocols