The Partition of Urinary Nitrogen after the Oral Administration of Glutamic Acid, Pyrrolidonecarboxylic Acid, Proline, and Hydroxyproline to Rabbits

Studies of the metabolism in vivo of proline and hydroxyproline and of the related pyrrolidonecarboxylic acid are not numerous. Many earlier redearches in which attempts were made to demonstrate relationships between these compounds and glutamic acid and ornithine are not convincing because of the fact that the rat growth procedure used at that time has now been shown to be inadequate. More recent experiments on the growth of young white rats have led to the belief that none of these amino acids is an essential component of the diet’ (1). Proline (3,4) and hydroxyproline (4) are stated to give rise to essentially the same amounts of extra glucose of the urine when administered to phlorhizinized dogs. The metabolism of pyrrolidonecarboxylic acid, the lactam of glutamic acid, has been investigated more frequently and with conflicting results (s-10). All are agreed that relatively little extra urea is excreted and that much of the ingested acid may appear unchanged in the urine. Any utilizat’ion presumably results from a slow transformation of pyrrolidonecarboxylic acid to glutamic acid, and the deamination of the latter with the formation of urea. However, in much of the work, details are lacking and the methods are not entirely satisfactory. The reverse reaction, the biological conversion of glutamic acid to pyrrolidonecarboxylic acid, has been demonstrated recently (11). When isotopic d-glutamic acid was fed to a rat, d-pyrrolidonecarboxylic acid was isolated from the urine. Evidence of the biological interconversion of proline, hydroxyproline, ornithine, and glutamic acid has also been obtained in experiments with isot,opic proline and a scheme of possible reactions has been present’ed (12). In connection with an investigation of urea formation in the intact organism of the rabbit after administration of a considerable number of