Ornithuric acid

Hippuric acid is a normal product of metabolism. It is produced in the kidney by the enzymic union of benzoic acid and glycine (Schmiede-berg and Bunge, 1877). In birds benzoic acid is rendered innocuous by combination with ornithine (aS-diamino-valeric acid) to form the dibenzoyl-derivative, so-called ornithuric acid (Jaffe). 

Ornithine or a, h-diamimrvalerianic Acid.—In 1877 JafTe obtained from the urine of birds, which he had fed with benzoic acid, dibenzoyl ornithine or ornithuric acid, and from this substance he prepared ornithine chloride. He regarded it as a diaminovalerianic acid, the first known representative of the series of diamino acids, but only in 1898 was the position of the two amino groups definitely determined by Ellinger, who obtained putrescine from it by putrefaction the identity of putrescine with tetramethylenediamine had been previously shown by... 

The dibenzoyl compound only differed from Jaffes ornithuric acid by being optically inactive. 

The domestic fowl has an unusual mechanism for handling benzoic acid. This acid is conjugated with ornithine, instead of glycine, and ornithuric acids are excreted after administration of many aromatic acids. Until recently, it was not known whether or not the fowl could synthesize conjugates of glucuronic acid, but this information has now been supplied by Sperber.108 He has shown that, in the hen, intramuscular injection of... 

This reaction was first reported by Schotten in 1884 and subsequently extended by Baumann in 1886. It is the acylation of alcohols and amines from acyl halide or anhydride in an aqueous alkaline solution (e.g., 1 M NaOH), and is generally known as the Schotten-Baumann reaction or Schotten-Baumann acylation. Occasionally, it is also referred to as the Schotten-Baumann method,or Schotten-Baumann esterification. Likewise, the formation of benzoyl ester under these conditions is called the Schotten-Baumann benzoylation." It is assumed that the reaction would perform well if carried out in a biphasic system of water and an immiscible organic solvent (e.g., CH2CI2), which has an important application in the acylation of amino acids.For example, p-nitrohippuric acid and dibenzoylornithine (ornithuric acid) all can be prepared under these conditions. 

McGilvery and Cohen later extended their studies to the formation of ornithuric acids from a- and 6-benzoyl-L-ornithine and p-aminobenzoic acid. They succeeded in obtaining enzymatic activity in an acetone powder of the sedimentable macroparticles of chicken liver homogenate, and found the conditions for the synthesis of the ornithuric acids, and the indications of the mechanisms involved, the same as in the synthesis of p-aminohippuric acid. 

It has not yet been reported whether Co A, which is necessary for the synthesis of hippuric acid, is also necessary for the synthesis of such analogs as p-aminohippuric and ornithuric acids. Probably Co A is required because their synthesis resembles that of hippuric acid in all other respects. 

Synthesis. Schulse and Winterstein (706, 708) prepared 1 g. of arginine nitrate by allowing a solution of cyanamide and ornithine to evaporate over sulfuric acid for three weeks while Sorensen et al. (747, 750) synthesized arginine nitrate by the reaction of cyanamide and a-benzoylamino-S-amino-n-valeric acid. Ornithine is readily synthesized from cyclopentanone by the methods described by Fox et al. (328) and Albertson and Archer (47) and ornithuric acid ( , -dibenzoylamino-n-valeric acid) is easily prepared by the benzoylation of ornithine. The other steps in the described syntheses of arginine are less satisfactory since they involve either tiie selective reaction of cyanamide with the 8-amino group of ornithine or the selective hydrolysis of the 8-benzoyl group of ornithuric acid. 

The only difference between the species is in the nature of the biliary metabolites. Thus aniline is excreted in the bile of the rat, dog, hen, rabbit, and guinea pig mainly as 2- and 4-aminophen3dglucuronide, while in the cat, the bile contains only 2-amiiiophenol. This is not unexpected, because the eat has a poor ability to form glucuranides (see Section III, A). Similarly, the hen is known to conjugate benzoic acid with ornithine instead of glycine (see Williams, 1959) and in this species, benzoic acid appears in the bile as ornithuric acid, while in the other species, apart from the dog, its... 

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