Development and inducibility of the hepatic and renal hippurate-synthesizing system in sparse-fur (spf) mutant mice with ornithine transcarbamylase deficiency.
The development of the hepatic and renal hippurate-synthesizing system, as represented by the overall reaction of the benzoyl CoA: glycine N-acyltransferase (EC 2.3.1.13) was studied in 0, 4, 8, 13, 17, 21-day and 8-week old sparse-fur (spf) mutant mice with X-linked ornithine transcarbamylase (OTC) deficiency. The enzyme system in mutant males (spf/Y) showed a retarded development in both liver and kidney cortex, which was statistically significant between 13 and 21 days of age, as compared to normal males (+/Y). Hippurate synthesis in preparations from adult (8-week old) spf/Y mice was not significantly different than the normal. Daily intraperitoneal injections of sodium benzoate in increasing concentrations (125-375 mg/kg), given between 17 and 21 days, did not cause any induction in spf/Y or +/Y mice. However, intraperitoneal sodium phenobarbital (80 mg/kg) increased the specific and total activities of the hepatic enzyme system in normal +/Y mice significantly. spf/Y tolerated a dose of 40 mg/kg only, which resulted in no significant increase of hepatic enzyme activity. The results indicate that barbiturates may induce the hippurate-synthesizing system, whereas benzoate treatment has no effect on changing its developmental profile.
Qureshi
I A
IA
Pediatric Research Center, Hôpital Sainte-Justine Université de Montréal, Quebec, Canada.
Lebel
S
S
Letarte
J
J
D000217:Acyltransferases / Q000096:biosynthesis; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D019817:Benzoic Acid; D004790:Enzyme Induction / Q000187:drug effects; D006626:Hippurates / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008817:Mice, Mutant Strains; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D010634:Phenobarbital / Q000494:pharmacology
D001565:Benzoates; D006626:Hippurates; D019817:Benzoic Acid; D000217:Acyltransferases; C020680:glycine acyltransferase; D010634:Phenobarbital