Free amino acid levels in serum and small intestine during the post-natal development of normal and sparse-fur mutant mice.

Ornithine transcarbamylase (OTC) is a mitochondrial enzyme which catalyzes the conversion of ornithine into citrulline. In sparse-fur (spf) mutant mice, in which both hepatic and small intestinal OTC are deficient, only small amounts of citrulline are released into the blood. To evaluate the fate of ornithine as well as the levels of substrates and products of these metabolic pathways in normal and OTC-deficient mice, we measured the concentration of free amino acids in small intestinal mucosa and serum during post-natal development. In control animals, ornithine, alanine and citrulline concentrations in intestinal mucosa increased as a function of age, while glutamine, leucine, valine and methionine levels decreased around the weaning period. In contrast, the serum concentration of these amino acids remained fairly constant. Major changes were observed in spf mice: the ornithine level remained low in intestinal tissue, citrulline concentration was significantly decreased in both intestinal tissue and blood, circulating levels of arginine and essential amino acids were drastically reduced in sucklings while plasma glutamine increased after weaning. These data confirm the validity of spf mice as a model for the study of nutritional requirements in OTC-deficient animals.