Metabolic functions of biotin. IV. The rôle of carbamyl-l-glutamic acid in the synthesis of citrulline by normal and biotin-deficient rats.

A characteristic consequence of a biotin deficiency in animals is a decreased ability to fix C402 into various tissue components including the amino acid arginine (1). Carbon dioxide is incorporated into arginine as a result of the conversion of ornithine to citrulline in the Krebs-Henseleit urea cycle (2). The methods developed by Cohen and Hayano (3, 4) for the synthesis of citrulline from ornithine, glutamate, COz, and ammonia by washed residue of rat liver homogenate have been applied to preparations from biotin-deficient rats (5). A greatly decreased rate of citrulline synthesis was observed in these preparations as compared to those obtained from rats fed an adequate diet. The specificity of this effect of biotin deficiency is attested to by the finding that essentially normal rates of citrulline synthesis were obtained in liver preparations from rats deficient in riboflavin or vitamin Bs and that injection of biotin into rats fed the egg white diet results in normal rates of citrulline synthesis 24 hours later (5). Since Cohen and Grisolia (6, 7) have shown that carbamyl-L-glutamate rather than glutamate is the actual catalytic intermediate in citrulline synthesis from ornithine, it seemed of importance to learn whether the effect of biotin nutriture on citrulline synthesis is manifested at a step prior to or subsequent to the reactions in which carbamyl glutamate participates.