Thyronamines are substrates for human liver sulfotransferases.
Sulfotransferases (SULTs) catalyze the sulfation of many endogenous compounds that include monoamine neurotransmitters, such as dopamine (DA), and thyroid hormones (iodothyronines). Decarboxylation of iodothyronines results in formation of thyronamines. In the mouse, thyronamines act rapidly in a nongenomic fashion to initiate hypothermia and decrease cardiac output and heart rate. These effects are attenuated after 1-4 h, and metabolism of thyronamines via sulfation may be a mechanism for termination of thyronamine action. We carried out this study to test thyronamine (T0AM), 3-iodothyronamine (T1AM), 3,5-diiodothyronamine (T2AM), and 3,5,3'-triiodothyronamine (T3AM) as substrates for human liver and cDNA-expressed SULT activities. We characterized several biochemical properties of SULTs using the thyronamines that acted as substrates for SULT activities in a human liver high-speed supernatant pool (n=3). T1AM led to the highest SULT activity. Activities with T0AM and T3AM were 10-fold lower, and there was no detectable activity with T2AM. Thyronamines were then tested as substrates with eight cDNA-expressed SULTs (1A1, 1A2, 1A3, 1C2, 1E1, 2A1, 2B1a, and 2B1b). Expressed SULT1A3 had the greatest activity with T0AM, T1AM, and T3AM, whereas SULT1A1 showed similar activity only with T3AM. Expressed SULT1E1 had low activity with each substrate. T1AM, the most active thyronamine pharmacologically, was associated with the greatest SULT activity of the thyronamines tested in the liver pool and in both the expressed SULT1A3 and SULT1E1 preparations. Our results support the conclusion that sulfation contributes to the metabolism of thyronamines in human liver and that SULT activities may regulate the physiological effects of endogenous thyronamines.
Pietsch
C A
CA
Veterans Affairs Medical Center, 4101 Woolworth Avenue, Omaha, Nebraska 68105, and University of California, San Francisco 94143, USA.
Scanlan
T S
TS
Anderson
R J
RJ
D000818:Animals; D001921:Brain / Q000201:enzymology; D019556:COS Cells; D002522:Chlorocebus aethiops; D005260:Female; D006325:Heart Atria / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D008954:Models, Biological; D009994:Osmolar Concentration; D015238:Sulfotransferases / Q000378:metabolism*; D013970:Thyronines / Q000378:metabolism; D014162:Transfection
D013970:Thyronines; C004547:thyronamine; D015238:Sulfotransferases