NITRITE FORMATION BY ENZYMATIC REACTION OF MANNITOL HEXANITRATE WITH GLUTATHIONE

¹ Edward Mallinckrodt Department of Pharmacology, Washington University School of Medicine, St. Louis, Mo.

Rat liver mitochondria contain an enzyme system which catalyzes a reaction between mannitol hexanitrate, glyceryl trinitrate, or erythrityl tetranitrate and glutathione to yield inorganic nitrite ions.

Since the reaction with glutathione is most rapid with mannitol hexanitrate and slowest with glyceryl trinitrate, rapid removal by this reaction cannot be the explanation why glyceryl trinitrate is less potent than mannitol hexanitrate as an uncoupler of aerobic phosphorylation in liver mitochondria. Because glyceryl trinitrate is very potent as a vasodilator, the question whether uncoupling has any relation to relaxation of vascular smooth muscle remains unsettled.

With mannitol hexanitrate the enzymatic reaction virtually stops when one nitrite ion has been formed per molecule of substrate added. The same may be true for the other nitrate esters.