PMID- 10199779
OWN - NLM
STAT- MEDLINE
DCOM- 19990421
LR  - 20061115
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 4
DP  - 1999 Apr
TI  - Characterization of human iodothyronine sulfotransferases.
PG  - 1357-64
AB  - Sulfation is an important pathway of thyroid hormone metabolism that facilitates 
      the degradation of the hormone by the type I iodothyronine deiodinase, but little
      is known about which human sulfotransferase isoenzymes are involved. We have
      investigated the sulfation of the prohormone T4, the active hormone T3, and the
      metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2) by human liver and kidney
      cytosol as well as by recombinant human SULT1A1 and SULT1A3, previously known as 
      phenol-preferring and monoamine-preferring phenol sulfotransferase, respectively.
      In all cases, the substrate preference was 3,3'-T2 >> rT3 > T3 > T4. The apparent
      Km values of 3,3'-T2 and T3 [at 50 micromol/L
      3'-phosphoadenosine-5'-phosphosulfate (PAPS)] were 1.02 and 54.9 micromol/L for
      liver cytosol, 0.64 and 27.8 micromol/L for kidney cytosol, 0.14 and 29.1
      micromol/L for SULT1A1, and 33 and 112 micromol/L for SULT1A3, respectively. The 
      apparent Km of PAPS (at 0.1 micromol/L 3,3'-T2) was 6.0 micromol/L for liver
      cytosol, 9.0 micromol/L for kidney cytosol, 0.65 micromol/L for SULT1A1, and 2.7 
      micromol/L for SULT1A3. The sulfation of 3,3'-T2 was inhibited by the other
      iodothyronines in a concentration-dependent manner. The inhibition profiles of
      the 3,3'-T2 sulfotransferase activities of liver and kidney cytosol obtained by
      addition of 10 micromol/L of the various analogs were better correlated with the 
      inhibition profile of SULT1A1 than with that of SULT1A3. These results indicate
      similar substrate specificities for iodothyronine sulfation by native human liver
      and kidney sulfotransferases and recombinant SULT1A1 and SULT1A3. Of the latter, 
      SULT1A1 clearly shows the highest affinity for both iodothyronines and PAPS, but 
      it remains to be established whether it is the prominent isoenzyme for sulfation 
      of thyroid hormone in human liver and kidney.
FAU - Kester, M H
AU  - Kester MH
AD  - Department of Internal Medicine III, Erasmus University Medical School, and
      Sophia Children Hospital, Rotterdam, The Netherlands.
FAU - Kaptein, E
AU  - Kaptein E
FAU - Roest, T J
AU  - Roest TJ
FAU - van Dijk, C H
AU  - van Dijk CH
FAU - Tibboel, D
AU  - Tibboel D
FAU - Meinl, W
AU  - Meinl W
FAU - Glatt, H
AU  - Glatt H
FAU - Coughtrie, M W
AU  - Coughtrie MW
FAU - Visser, T J
AU  - Visser TJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Isoenzymes)
RN  - EC 2.8.2.- (Sulfotransferases)
RN  - EC 2.8.2.- (iodothyronine sulfotransferase)
SB  - AIM
SB  - IM
MH  - Adult
MH  - Humans
MH  - Isoenzymes/genetics/metabolism
MH  - Kinetics
MH  - Substrate Specificity
MH  - Sulfotransferases/genetics/*metabolism
EDAT- 1999/04/13 00:00
MHDA- 1999/04/13 00:01
CRDT- 1999/04/13 00:00
PHST- 1999/04/13 00:00 [pubmed]
PHST- 1999/04/13 00:01 [medline]
PHST- 1999/04/13 00:00 [entrez]
AID - 10.1210/jcem.84.4.5590 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Apr;84(4):1357-64. doi: 10.1210/jcem.84.4.5590.