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

Abstract

Phenol sulfotransferase was isolated in 100,00% supernatant fractions prepared from postmortem samples of human brain. Since phenol sulfotransferase (PST) has been shown to conjugate the amine neurotransmitters 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 p~, dopamine (DA) was the best substrate examined and was followed in decreasing order of activity by 3-methoxytyramine (3-MT), tyramine, norepinephrine, 3-methoxy-4hydroxyphenylethyleneglycol, octopamine. 5-hydroxytryptamine, and dihydroxyphenylethyleneglycol. At a substrate concentration of 100 p~ 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 FM. Using PST isolated in 1 0 0 , 0 0~ supernatant fractions from human brain, the K , value for DA was found to be 5.0 p~, while the K , value for the sulfate-donor 3'-phosphoadenosine-S'-phosphosulfate was 0.25 p~. The ratio of 3-0-to 4-0-DA-sulfate formed in vitro by human brain PST was found to be about 4: 1. In addition, both the 3-0-and 4-0-esters were found not to be deaminated by human brain mitochondria1 MAO. The relative role of PST with respect to M A 0 and catechol-0-methyltransferase in the degradation of the biogenic amine neurotransmitters in human brain is discussed. K e y words: Sulfotransferase-Dopamine-Catecholamines-Amine metabolism.

Electron Paramagnetic Resonance Study on Free Radical Scavenging and/or Generating Activity of Dopamine-4-O-sulfate.

“…In the circulation, 99% of dopamine was transformed into a sulfoconjugated form 31) by phenosulfotransferase which is localized in the gut, 32) liver, 33) kidney, 34) brain, 35) and platelets. 36) And dopamine sulfate is partially hydrolyzed by human arylsulfatase A, B and C in vitro, then converted to dopamine.…”

Association of SULT1A1 Phenotype and Genotype with Prostate Cancer Risk in African-Americans and Caucasians

“…It is found in most epithelial tissues and is the most abundant hepatic sulfotransferase, with levels in that tissue 10 times greater than all of the other isoforms (20,21). SULT1A1 catalyzes the sulfation of a host of structurally diverse compounds, such as small phenols, steroids, iodothyronines, environmental estrogen-like compounds, and heterocyclic and aromatic amines (22,33).…”

Urinary MHPG sulfate as a marker of central norepinephrine metabolism: a commentary

“…Indeed only phenolsulfotransferase (PST) has been detected in brains of mammals--including man--whereas both phenolsulfotransferase and glucuronyltransferase activities have been found in peripheral tissues (Fddes and Meek, 1974;Rein et al, 1981Rein et al, , 1984Renskers et al, 1980;Wong, 1976). MHPG exists in urine as both conjugates--the sulfate and the glucuronide whereas MHPG sulfate is the major--or the only---conjugate in brain (Table 1, Table 3).…”

“…In human brain and rat brain, PST is found primarily in the cytosolic fraction and to a lesser extent in synaptosomes (Renskers et al, 1980: Rivett et al, 1984van Kempen, 1975). Lesioning studies with kainic acid (Rivett et al, 1984) or 6-OH-DA (Buu, 1985) have suggested that, in rat striatum, PST may be located within specific neurons other than the dopaminergic terminals.…”