Human Brain Phenol Sulfotransferase: Biochemical Properties and Regional Localization

Abstract

Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of catecholamines and phenol and catechol drugs. The human blood platelet contains a thermolabile (TL) form of PST that catalyzes the sulfate conjugation of dopamine and other monoamines and a thermostable (TS) form that catalyzes the sulfate conjugation of micromolar concentrations of phenol and p-nitrophenol. Experiments were performed to determine whether the brain contains forms of PST analogous to the TL and TS forms found in the human platelet and to determine whether there are regional variations in human brain PST activity. The human brain contains at least 2 forms of PST, forms that are similar to the platelet TS and TL forms of the enzyme with respect to substrate specificity, apparent Km, thermal stability and sensitivity to inhibitors. Optimal conditions were determined for the measurement of these 2 activities in brain homogenates. The stability of PST activities in the human brain after death was determined in 5 samples of cerebral cortex that were obtained during clinically indicated neurosurgical procedures. An average of 76 .+-. 8% and 80 .+-. 9% (mean .+-. SEM [standard error of the mean]) of the basal TL and TS PST activities, respectively, remained in these 5 samples of cerebral cortex after 8 h of storage under simulated post-mortem conditions. Six human brains were then obtained < 8 h after death from patients who had no neurological disease prior to death. The mean activities of the TL and TS forms of PST were measured in 17 different regions of the 6 brains. If the pituitary was excluded from consideration, TL and TS PST activities both varied about 5-fold among these regions and both activities were highest in cerebral cortex. The average TS activity in the anterior pituitary, a tissue of non-neural origin embryoloigically, was 6.5-fold greater than the highest average TS PST activity found in cerebral cortex.