Effect of urease-induced hyperammonemia on metabolism of guanidino compounds.
We previously reported that guanidino compounds produced by the catabolism of arginine play an important role in the pathophysiology of acute hyperammonemia. In order to understand the metabolism of guanidino compounds during sustained hyperammonemia, we investigated the effect of intraperitoneal urease injection (800 IU/kg) on the levels of guanidino compounds in blood, liver, kidney, and brain of rats. Control rats received an equal volume of saline. Eight hours following injection, rats were sacrificed and blood and tissues were removed. Ammonia and urea were determined by enzymatic and colorimetric assays, respectively. Guanidino compounds were analyzed by high-performance liquid chromatography. Blood and tissue ammonia were significantly increased and urea decreased in urease-treated animals. Blood and kidney arginine levels were significantly decreased although hepatic arginine was increased following urease injection. Elevated hepatic arginine may be due to the rapid conversion of urea to ammonia by urease and the development of a futile urea cycle. Catabolites produced by the transamidination of arginine were significantly decreased in the blood, liver, kidney, and brain of urease-treated rats, whereas acetylation of hepatic arginine to alpha-N-acetylarginine was increased. Blood and tissue guanidinosuccinic acid levels were not elevated during urease induced hyperammonemia, supporting the hypothesis that urea is a precursor for the synthesis of guanidinosuccinic acid.
Meert
K L
KL
Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit 48201.
Deshmukh
D R
DR
Marescau
B
B
Ghole
V S
VS
De Deyn
P P
PP
Sarnaik
A P
AP
D000641:Ammonia / Q000097:blood*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D006146:Guanidines / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013386:Succinates / Q000378:metabolism; D014508:Urea / Q000378:metabolism; D014510:Urease / Q000494:pharmacology*
D006146:Guanidines; D013386:Succinates; C001318:guanidinosuccinic acid; D000641:Ammonia; D014508:Urea; D001120:Arginine; D014510:Urease