Characterization of human liver thermostable phenol sulfotransferase (SULT1A1) allozymes with 3,3',5-triiodothyronine as the substrate.
Sulfotransferase 1A1 (SULT1A1) (thermostable phenol sulfotransferase, TS PST1, P-PST) is important in the metabolism of thyroid hormones. SULT1A1 isolated from human platelets displays wide individual variations not only in the levels of activity, but also in thermal stability. The activity of the allelic variant or allozyme SULT1A1*1, which possesses an arginine at amino acid position 213 (Arg213) has been shown to be more thermostable than the activity of the SULT1A1*2 allozyme which possesses a histidine at this position (His213) when using p-nitrophenol as the substrate. We isolated a SULT1A1*1 cDNA from a human liver cDNA library and expressed both SULT1A1*1 and SULT1A1*2 in eukaryotic cells. The allozymes were assayed using iodothyronines as the substrates and their biochemical properties were compared. SULT1A1*1 activity was more thermostable and more sensitive to NaCl than was SULT1A1*2 activity when assayed with 3,5,3'-triiodothyronine (T(3)). Sensitivities to 2,6-dichloro-4-nitrophenol (DCNP) and apparent K(m) values for SULT1A1*1 and for SULT1A1*2 with iodothyronines were similar. Based on K(m) values, the preferences of these SULT1A1 allozymes for iodothyronine substrates were the same (3,3'-diiodothyronine (3,3'-T(2))>3', 5',3-triiodothyronine (rT(3))>T(3)>thyroxine (T(4))>>3,5-diiodothyronine (3,5-T(2))). SULT1A1*1 activity was significantly higher than the SULT1A1*2 activity with T(3) as the substrate. Potential differences in thyroid hormone sulfation between individuals with predominant SULT1A1*1 versus SULT1A1*2 allozymes are most likely due to differences in catalytic activity rather than substrate specificity.
Li
X
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Creighton University School of Medicine, Omaha, Nebraska 68105, USA.
Clemens
D L
DL
Cole
J R
JR
Anderson
R J
RJ
D000483:Alleles; D000595:Amino Acid Sequence; D015239:Arylsulfotransferase; D018076:DNA, Complementary / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015723:Gene Library; D006358:Hot Temperature; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D013696:Temperature; D014285:Triiodothyronine, Reverse
D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D014285:Triiodothyronine, Reverse; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human