Triiodothyronine: A substrate for the thermostable and thermolabile forms of human phenol sulfotransferase

The enzyme(s) responsible for the sulfate conjugation of L-T³ in man has not been characterized. T³ sulfotransferase (T³-ST) activity was characterized in normal human liver tissue obtained during clinically indicated surgical resection. Subcellular distribution studies showed that the T³-ST activity was localized to the cytoplasmic fraction. This finding raised the possibility that T³-ST activity might be similar to the 2 previously identified forms of cytoplasmic phenol sulfotransferase (PST) found in human tissue. A thermostable (TS) form of PST catalyzes the sulfate conjugation of micromolar concentrations of p-nitrophenol, and a thermolabile (TL) form catalyzes the sulfate conjugation of dopamine and other monoamines. Thermal stability and enzyme inhibitor experiments showed that T³-ST activity in pooled liver homogenates was very similar to the TS form of PST. The apparent similarity of T³-ST to TS PST was studied further by measuring T³-ST, TS PST, and TL PST activities in 20 individual liver samples. T³- ST activities correlated significantly with TS PST activities (r = 0.939; P < 0.001) measured with p-nitrophenol, but not with TL PST activities (r = -0.118; P > 0.6) measured with dopamine. However, sulfation of T³ by the TL form of the enzyme might have been masked by the 18-fold higher specific activity of TS than TL PST in human liver homogenates. When the two forms of PST were separated by ion exchange chromatography, T³ was found to be a substrate for both the TS and TL forms of PST. “True” Km values for T³ were similar for TS and TL PST (81 and 127 μM, respectively).