Expression patterns of ammonia-metabolizing enzymes in the liver, mesonephros, and gut of human embryos and their possible implications.

Human and ungulate embryos can catabolize amino acids for energy production, whereas rodent embryos cannot, raising the question whether studies of rodent model systems are suitable for extrapolation to the human situation. Therefore, we investigated the expression of the amino acid- and ammonia-metabolizing enzymes glutaminase, glutamate dehydrogenase, glutamine synthase, carbamoylphosphate synthase, and arginase immunohistochemically in a graded series of human embryos and fetuses. During human development the expression of these enzymes is first seen in the liver, then in the mesonephric kidney, and finally in the small intestine. Such a simultaneous expression of nitrogen-metabolizing enzymes was not seen in any other organ. The early appearance of the enzymes involved in amino acid and ammonia metabolism in the human liver, compared to, for example, the rat liver, suggests that catabolism of amino acids may provide an important supply of metabolic energy for the human embryo. The coexpression of glutaminase, glutamate dehydrogenase, and carbamoylphosphate synthase, but not of arginase, in the mesonephros and the small intestine suggests that these organs are involved in the biosynthesis of intermediates of the ornithine cycle, e.g., arginine or citrulline. From a comparison of the developmental appearance of ornithine cycle enzymes in different mammalian species we postulate that an early appearance of these enzymes is generally associated with a relatively slow prenatal growth rate and the use of amino acids as metabolic fuel.