Identification of 3,3'-diiodothyroacetic acid sulfate: a major metabolite of 3,3',5-triiodothyronine in propylthiouracil-treated rats.
The sulfate conjugate 3, [3'-125I] diiodothyroacetic acid (3,3'-TA2S) was discovered in plasma, and occasionally in bile, of 6-propyl-2-thiouracil-treated rats after administration of [125I]T3. The identification of this T3 metabolite was based on the following evidence: 1) the compound co-eluted in two different HPLC systems with synthetic 3,3'-TA2S; 2) its chromatographic behavior on Sephadex LH-20 was characteristic for a conjugated iodothyronine derivative; and 3) the metabolite was hydrolyzed by arylsulfatase and the liberated product comigrated with synthetic 3,3'-TA2 on HPLC. Marked accumulation of 3,3'-TA2S was observed only in rats with impaired type I deidodinase activity but not in controls. Furthermore, plasma and biliary 3,3'-TA2S levels varied with the experimental conditions such as anesthesia, i.e. both were increased in ketamine-anesthetized over pentobarbital-anesthetized animals. It was not possible to indicate the exact pathway through which 3,3'-TA2S is generated from T3; neither is it known how much of T3 is actually metabolized via 3,3'-TA2S. However, the significant plasma 3,3'-TA2S levels, even in unanesthetized animals, illustrate the physiological relevance of this T3 metabolite.
Department of Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands.
M
M
Rutgers
F A
FA
Heusdens
F
F
Bonthuis
S J
SJ
Rooda
T J
TJ
Visser
D000758:Anesthesia; D000818:Animals; D001192:Arylsulfatases / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid; D004104:Diiodothyronines / Q000097:blood / Q000378:metabolism*; D006868:Hydrolysis; D007649:Ketamine; D008297:Male; D010424:Pentobarbital; D051381:Rats; D011919:Rats, Inbred Strains; D013970:Thyronines / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
D004104:Diiodothyronines; D013970:Thyronines; D014284:Triiodothyronine; D007649:Ketamine; C065721:3,3'-diiodothyroacetic acid sulfate; D001192:Arylsulfatases; D010424:Pentobarbital