Formamidine group transfer in extracts of human pancreas, liver, and kidney

Abstract

Extracts of human pancreas, liver, and kidney catalyze transfer of the formamidine (-C(NH)NH 2 ) group from certain donor compounds to hydroxylamine. Amidinotransferase activity of human liver is approximately equal to that of kidney; human pancreas has 5 times the activity of liver and kidney. No significant amidinotransferase activity was observed in extracts from livers of rat, rabbit, or dog; monkey liver has half the activity of human liver. Formamidine donors include, in descending order of activity: arginine, guanidinoacetate, 4-guanidinobutyrate, and 3-guanidinopropionate. l -2-Amino-4-guanidinobutyrate and l -2-amino-3-guanidinopropionate have no donor activity. The most effective inhibitors of each of these transamidinations are, in descending order, ornithine, glycine, and norvaline. It is suggested that most, if not all, of the foregoing reactions are catalyzed by l -arginine: glycine amidinotransferase (EC 2.6.2.1) and that, unlike the case of certain lower mammals, the liver of primates can catalyze the first step in creatine biosynthesis. Several methods of assaying for amidinotransferase in the presence of high levels of arginase (EC 3.5.3.1) are illustrated. To explain the observed enzyme inhibitions, two tentative models of the enzymic site of human pancreatic amidinotransferase are considered: one involving partially overlapping acceptor-specific sites, the other involving acceptor sites which are spacially separated but subject to distortion by adsorbed acceptors.