VARIABLE GLYCERYL DINITRATE FORMATION AS A FUNCTION OF GLUTATHIONE-S-TRANSFERASE

Nitroglycerin (GTN) has been used as the drug of choice in the treatme nt of angina pectoris, It has been shown that some glutathione S-trans ferases (GSTs) catalyze the metabolic conversion from GTN to glyceryl dinitrates (GDNs). In this study, we examined the substrate specificit y of GSTs for GTN. Alpha and mu GSTs were isolated from porcine liver and intestinal mucosa by means of CM-cellulose and glutathione-affinit y column chromatography. Mu GSTs degraded GTN time-dependently and for med 1,3-GDN in preference to 1,2-GDN at a ratio (1,2-GDN/I,3-GDN) of 0 .61, whereas alpha GSTs formed twice as much I,2-GDN as I,3-GDN. These results showed that two GST families participate in the metabolic con version of GTN at different hydrolyzing portions of the nitrogroups.