Human liver steroid sulphotransferase sulphates bile acids.
The sulphation of bile acids is an important pathway for the detoxification and elimination of bile acids during cholestatic liver disease. A dehydroepiandrosterone (DHEA) sulphotransferase has been purified from male and female human liver cytosol using DEAE-Sepharose CL-6B and adenosine 3',5'-diphosphate-agarose affinity chromatography [Falany, Vazquez & Kalb (1989) Biochem. J. 260, 641-646]. Results in the present paper show that the DHEA sulphotransferase, purified to homogeneity, is also reactive towards bile acids, including lithocholic acid and 6-hydroxylated bile acids, as well as 3-hydroxylated short-chain bile acids. The highest activity towards bile acids was observed with lithocholic acid (54.3 +/- 3.6 nmol/min per mg of protein); of the substrates tested, the lowest activity was detected with hyodeoxycholic acid (4.2 +/- 0.01 nmol/min per mg of protein). The apparent Km values for the enzyme are 1.5 +/- 0.31 microM for lithocholic acid and 4.2 +/- 0.73 microM for taurolithocholic acid. Lithocholic acid also competitively inhibits DHEA sulphation by the purified sulphotransferase (Ki 1.4 microM). No evidence was found for the formation of bile acid sulphates by sulphotransferases different from the DHEA sulphotransferase during purification work. The above results suggest that a single steroid sulphotransferase with broad specificity encompassing neutral steroids and bile acids exists in human liver.
Radominska
A
A
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock 72205.
Comer
K A
KA
Zimniak
P
P
Falany
J
J
Iscan
M
M
Falany
C N
CN
D000293:Adolescent; D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000378:metabolism*; D001667:Binding, Competitive; D002648:Child; D005260:Female; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000302:isolation & purification / Q000378:metabolism*; D013464:Sulfuric Acids / Q000378:metabolism; D013466:Sulfurtransferases / Q000302:isolation & purification / Q000378:metabolism*
D001647:Bile Acids and Salts; D013464:Sulfuric Acids; D013466:Sulfurtransferases; D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase; C044251:steroid sulfotransferase