Quantitative evaluation of the expression and activity of five major sulfotransferases (SULTs) in human tissues: the SULT "pie".
Expression levels of the major human sulfotransferases (SULTs) involved in xenobiotic detoxification in a range of human tissues (i.e., SULT "pies") are not available in a form allowing comparison between tissues and individuals. Here we have determined, by quantitative immunoblotting, expression levels for the five principal human SULTs-SULT1A1, SULT1A3/4, SULT1B1, SULT1E1, and SULT2A1-and determined the kinetic properties toward probe substrates, where available, for these enzymes in cytosol samples from a bank of adult human liver, small intestine, kidney, and lung. We produced new isoform-selective antibodies against SULT1B1 and SULT2A1, which were used alongside antibodies against SULT1A3 and SULT1A1 previously produced in our laboratory or available commercially (SULT1E1). Expression levels were derived using purified recombinant enzymes to construct standard curves for each individual isoform and immunoblot. Substantial intertissue and interindividual differences in expression were observed. SULT1A1 was the major enzyme (>50% of total, range 420-4900 ng/mg cytosol protein) in the liver, followed by SULT2A1, SULT1B1, and SULT1E1. SULT1A3 was completely absent from this tissue. In contrast, the small intestine contained the largest overall amount of SULT of any of the tissues, with SULT1B1 the major enzyme (36%), closely followed by SULT1A3 (31%), and SULT1A1, SULT1E1, and SULT2A1 more minor forms (19, 8, and 6% of total, respectively). The kidney and lung contained low levels of SULT. We provide a unique data set that will add value to the study of the role and contribution of sulfation to drug and xenobiotic metabolism in humans.
Riches
Zoe
Z
Division of Medical Sciences, Centre for Oncology and Molecular Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
Stanley
Emma L
EL
Bloomer
Jackie C
JC
Coughtrie
Michael W H
MW
D000328:Adult; D000368:Aged; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007421:Intestine, Small / Q000737:chemistry / Q000201:enzymology; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000737:chemistry / Q000201:enzymology; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008168:Lung / Q000737:chemistry / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D015238:Sulfotransferases / Q000032:analysis* / Q000096:biosynthesis* / Q000235:genetics; D014018:Tissue Distribution / Q000502:physiology; D055815:Young Adult
D007527:Isoenzymes; D015238:Sulfotransferases
Biochem Pharmacol. 2007 Jul 15;74(2):352-8
17506995
Drug Metab Dispos. 2006 May;34(5):880-6
16467132
Biochem Biophys Res Commun. 2000 Oct 14;277(1):236-45
11027669
Mol Pharmacol. 1998 Dec;54(6):942-8
9855620
Drug Metab Dispos. 2003 Jun;31(6):697-700
12756199
Toxicol Appl Pharmacol. 2003 Mar 15;187(3):186-97
12662902
J Histochem Cytochem. 2003 Dec;51(12):1655-64
14623933
Biochim Biophys Acta. 2005 Jun 20;1724(1-2):119-26
15878639
Pharmacogenomics J. 2002;2(5):297-308
12439736
J Clin Endocrinol Metab. 1999 Jul;84(7):2577-80
10404840
Br J Pharmacol. 2003 Aug;139(8):1373-82
12922923
Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4
388439
Pharmacogenomics J. 2002;2(1):48-56
11990382
Drug Metab Rev. 2004 Oct;36(3-4):703-22
15554243
Biochem Biophys Res Commun. 1994 Jan 28;198(2):707-11
8297382
Chem Biol Interact. 1994 Jun;92(1-3):351-62
8033269
Mol Pharmacol. 1998 Feb;53(2):274-82
9463486
Nat Struct Biol. 1997 Nov;4(11):904-8
9360604
J Clin Endocrinol Metab. 2001 Jun;86(6):2734-42
11397879
Endocrinology. 1994 Feb;134(2):982-9
8299591
Biochem Pharmacol. 1999 Aug 15;58(4):605-16
10413297
Nature. 1970 Aug 15;227(5259):680-5
5432063
J Clin Endocrinol Metab. 1999 Apr;84(4):1357-64
10199779
Mol Cell Endocrinol. 2005 Aug 30;240(1-2):32-42
16024168
Hum Mol Genet. 2007 Mar 1;16(5):463-70
17189289
Pharmacogenetics. 2004 Mar;14(3):199-211
15167709
Carcinogenesis. 1998 Nov;19(11):2007-11
9855017
J Steroid Biochem Mol Biol. 2001 Jun;77(4-5):261-9
11457664
Br J Clin Pharmacol. 1986 Nov;22(5):587-93
3790406
Pharmacogenomics J. 2004;4(1):54-65
14676822
J Pharmacol Exp Ther. 2006 Mar;316(3):1310-7
16339912
J Biol Chem. 2003 May 16;278(20):17838-44
12637555
Mol Hum Reprod. 1999 Nov;5(11):995-1002
10541560
Chem Biol Interact. 2000 Dec 1;129(1-2):141-70
11154739
Clin Exp Pharmacol Physiol Suppl. 1999 Apr;26:S41-53
10386253
Biochem J. 2007 Jun 1;404(2):207-15
17335415
J Pharmacol Exp Ther. 1994 Jul;270(1):414-23
8035341
Biochim Biophys Acta. 1973 Dec 19;327(2):365-74
4778939
Xenobiotica. 2003 Nov;33(11):1139-48
14660177
Toxicol Sci. 2006 Mar;90(1):5-22
16322073
Biochem Pharmacol. 2003 Dec 1;66(11):2089-97
14609733
Endocrinology. 2000 May;141(5):1897-900
10803601
J Biol Chem. 1998 May 1;273(18):10888-92
9556564
J Steroid Biochem Mol Biol. 1996 Dec;59(5-6):467-78
9010352
Endocr Rev. 2002 Oct;23(5):703-32
12372849
Pharmacogenomics J. 2007 Apr;7(2):133-43
16801938
J Steroid Biochem Mol Biol. 2007 Nov-Dec;107(3-5):202-10
17662596
J Biol Chem. 1951 Nov;193(1):265-75
14907713