Unique properties of a renal sulfotransferase, St1d1, in dopamine metabolism.
Although catecholamine sulfation is higher in the kidney than in the liver of mice, no detectable amounts of previously reported sulfotransferases (STs) such as St1a, St1b, St1c, and St1e were expressed in mouse kidney cytosols. A new sulfotransferase (St1d1) cDNA was isolated from kidney cDNA library of BALB/c strain by reverse transcription-polymerase chain reaction (RTPCR) using information from expressed sequence tags (EST) database. The cDNA sequence resembled that of cDNA reported previously (AA238910) (Sakakibara et al., 1998) but differed in two amino acids, (206)Q/K and (216)Y/F, in the deduced amino acid sequence. The St1d1 expressed had unique substrate specificities for catecholamine derivatives, which preferred their deaminated metabolites rather than their parent amines. St1d1 showed the highest activity toward 3,4-dihydroxyphenylacetic acid (230.2 +/- 2.69 nmol/mg/min) among the examined substrate. St1d1 protein was abundant in kidney, followed by liver, lung, and uterus. Furthermore, an addition of anti-St1d1 serum in the cytosolic reaction mixture resulted in complete inhibition of the sulfotransferase activity suggesting a major role of St1d1 on catecholamine sulfations. No human ST1D ortholog was detected at both mRNA and protein levels, although ST1A5 selectively catalyzing parent amine sulfation was detected in human kidney. These results indicate the functional basis of sulfation and the clear species difference on renal catecholamine metabolisms in mice and humans.
Shimada
Miki
M
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki Aoba, Aoba-ku, Sendai 980-8578, Japan. shimada@mail.pharm.tohoku.ac.jp
Terazawa
Reiko
R
Kamiyama
Yoshiteru
Y
Honma
Wataru
W
Nagata
Kiyoshi
K
Yamazoe
Yasushi
Y
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015238:Sulfotransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
C431463:SULT1D1 sulfotransferase; D015238:Sulfotransferases; D004298:Dopamine