US EPA

2251193 

Journal Article 

Metabolism of Inorganic Nitrite and Nitrate Esters. II. The Enzymatic Reduction of Nitroglycerin and Erythritol Tetranitrate by Glutathione 

Heppel, LA; Hilmoe, RJ 

1956 

Yes 

Journal of Biological Chemistry
ISSN: 0021-9258
EISSN: 1083-351X 

NIOSH/00133400 

183 

129-138 

The enzymatic reduction of nitroglycerin (55630) and erythritol-tetranitrate (7297258) by glutathione (70188) (GSH) was investigated. A spontaneous reaction between GSH and the test materials resulted in formation of inorganic nitrite and oxidized GSH. Inorganic nitrite was determined in silver-chloride filtrates and GSH was determined in sulfosalicylic-acid filtrates. Nitrite formation increased as pH became more alkaline. Reduced GSH could be replaced by cysteine (52904) or cysteinylglycine (19246185). A nitrite forming enzyme was purified from hog liver acetone powder by fractionation with ammonium-sulfate and alcohol, and selective elution from calcium-phosphate gel. The enzyme catalyzed the reaction between nitroglycerin and GSH and between erythritol-tetranitrate and GSH. Enzyme activity was measured in terms of amount of nitrite formed over time. The enzyme had a pH optimum of between 7 and 8 and was sensitive to cupric salts. The enzyme did not stimulate the reaction between cysteine and nitroglycerin, nitrite was formed and the rate and extend of the reaction could be correlated with GSH content of the extracts. The authors postulate that these results explain the decomposition of nitroglycerin and erythritol-tetranitrate in the presence of blood and other tissue preparations, while they remain stable in neutral aqueous solutions.