Sulfation of Dopamine and Other Biogenic Amines by Human Brain Phenol Sulfotransferase

Abstract: Phenol sulfotransferase was isolated in 100,000g supernatant fractions prepared from postmortem samples of human brain. Since phenol sulfotransferase (PST) has been shown to conjugate the amine neurotransmit‐ters in vivo, the abilities of eight different biogenic amines and structurally related compounds to act as substrates for PST were studied. These experiments demonstrate that at a concentration of 20 μM, dopamine (DA) was the best substrate examined and was followed in decreasing order of activity by 3‐methoxytyramine (3‐MT), tyramine, norepinephrine, 3‐methoxy‐4‐hydroxyphenylethyleneglycol, octopamine, 5‐hydroxytryptamine and dihydroxyphenylethyleneglycol. At a substrate concentration of 100 /UM the relative order of activity was altered, so that tyramine became the most rapidly conjugated substrate while the activity of DA and 3‐MT relative to the other substrates tested was diminished. This change in substrate affinity with differing substrate concentrations can be explained, at least for DA, by the occurrence of apparent substrate inhibition at concentrations above 25 to 30 μM. Using PST isolated in 100,000g supernatant fractions from human brain, the K_m value for DA was found to be 5.0 μM, while the K_m value for the sulfate‐donor 3′‐phosphoadenosine‐5′‐phosphosulfate was 0.25 μM. The ratio of 3‐O‐ to 4‐O‐DA‐sulfate formed in vitro by human brain PST was found to be about 4: 1. In addition, both the 3‐O‐ and 4‐O‐esters were found not to be deaminated by human brain mitochondrial MAO. The relative role of PST with respect to MAO and catechol‐O‐methyltransferase in the degradation of the biogenic amine neurotransmitters in human brain is discussed.