Reduced ornithine transcarbamylase activity does not impair ureagenesis in Otc(spf-ash) mice.

Abstract

Mouse models for urea cycle disorders have been available for the past 30 y; however, until now, no measurements of urea production in vivo have been conducted. Urea entry rate was determined in Otc(spf-ash) and littermate controls employing a primed-continuous infusion of 15N15N urea. A saline infusion control, a complete mixture of amino acids (AA), or a glycine-alanine (GA) mixture was infused at 86 (AA1 and GA1) and 172 mg N.kg(-1).h(-1) (AA2 and GA2) to impose a defined nitrogen load on the urea cycle. Urea entry rate and plasma urea concentration increased (P < 0.001) as a consequence of the increase in the infusion rate of the complete mixture of amino acids, but the 2 genotypes did not differ (P = 0.96 and P = 0.44, respectively). The infusion of the GA mixture, however, decreased (P < 0.001) the plasma urea concentration and urea entry rate in Otc(spf-ash) mice compared with controls. At the highest level (GA2), urea entry rate was further depressed (P < 0.001), Otc(spf-ash) mice became hyperammonemic (1701 +/- 150 micromol/L), and hyperammonemic symptoms were evident. An acute hepatic enlargement (P < 0.001) was also evident in Otc(spf-ash) mice infused with GA2. These results show that despite vestigial OTC activity, Otc(spf-ash) mice were able to maintain ureagenesis at the same rate of control animals when a complete mixture of amino acids was infused. This implies that Otc(spf-ash) mice are able to dispose of ammonia, without apparent adverse effects, when a balance mixture of amino acids is provided, despite reduced enzyme activity.

• Authors: Juan C Marini, Brendan Lee, Peter J Garlick
• Journal: The Journal of nutrition (J Nutr) Vol. 136 Issue 4 Pg. 1017-20 (Apr 2006) ISSN: 0022-3166 [Print] United States
• PMID: 16549467 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Amino Acids
• Dipeptides
• Ammonia
• Urea
• N-glycylalanine
• Ornithine Carbamoyltransferase

Topics

• Amino Acids (administration & dosage)
• Ammonia (blood, metabolism)
• Animals
• Dipeptides (administration & dosage)
• Food Deprivation
• Genotype
• Mice
• Mice, Mutant Strains
• Mutation
• Ornithine Carbamoyltransferase (genetics, metabolism)
• Ornithine Carbamoyltransferase Deficiency Disease
• Regression Analysis
• Urea (blood, metabolism)
• Weight Loss