Deamidation of glutamine by increased plasma gamma-glutamyltransferase is a source of rapid ammonia formation in blood and plasma specimens

Owing to increased enzymatic hydrolysis of glutamine, additional ammonia is formed in blood and plasma specimens with increased gamma-glutamyltransferase activity (gamma-GT, EC 2.3.2.2.). The close correlation between gamma-GT and glutaminase (EC 3.5.1.2) activities (r = 0.97) in plasma, the inhibition with 6-diazo-5-oxo-L-norleucin or borate plus serine, and the activation with maleate clearly show that gamma-GT itself is the glutamine-deamidating enzyme in plasma. Under pathological conditions, increased gamma-GT activity can increase the rate of ammonia formation in plasma more than 30-fold the mean values of healthy subjects. Increased in vitro formation of ammonia caused by increased gamma-GT activity is an important source of false-positive findings in ammonia determination. Because of the high prevalence of pathological gamma-GT activities in clinical populations, blood specimens for ammonia analysis should be preserved by addition of borate plus serine.