BIOTRANSFORMATION IN MONKEY BRAIN - COUPLING OF SULFATION TO GLUTATHIONE CONJUGATION

Phenol sulfotransferase (PST, EC 2.8.2.1) and glutathione-S-transferas e (GST, EC 2.5.1.18), the phase II biotransformation enzymes inactivat e many exo- and endogenous compounds. The effect of PST substrates (ca techolamines, simple phenols, selected phenolic drugs) and PST product s (phenolic sulfates) on GST activity was investigated to identify pos sible interactions between sulfation and glutathione conjugation in th e brain. Two soluble forms of PST and two forms of GST were isolated f rom monkey (Rhesus macacus) brain cortex. Catecholamines, hypertensive and hypotensive drugs which are sulfated by monkey brain PSTs slightl y inhibit the activity of brain GSTs. The greatest inhibitory effect w as observed with neurotoxic compounds such as 6-OHDA and manganese. Th e commonly used analgesic drugs inhibit both GST forms. These enzymes are also inhibited by phenacetin, the precursor of paracetamol, and pr ototype salicylates such as sodium salicylate and acetylsalicylic acid . The effect of simple phenols and their sulfated metabolites on GST a ctivity varies. The obtained results point to a possible interaction b etween sulfation and glutathione conjugation in vivo since many physio logically, therapeutically and toxicologically active compounds which are sulfated by brain phenol sulfotransferases may be bound by brain g lutathione-S-transferases. These compounds may lose their activity (on being bound to GST) and expose the brain to the toxic electrophiles ( by decreasing GST activity).