The metabolism of gluconic acid.

In a previous study the appearance of deuterioglucose in the urine of the phlorhizinized rat was shown to follow the injection of meso-inositol which had been tagged with deuterium in the carbon-bound positions (1). This result was taken as proof of the glucogenic nature of inositol in the rat and has led the authors to the investigation of another possible glucose precursor, gluconic acid, by a similar approach. Early studies of the fate of gluconic acid in the intact animal have related chiefly to its oxidation. Thus it has been demonstrated that a large portion of gluconic acid administered is utilized even by the diabetic organism (2-5) and it has been claimed that saccharic acid is one of the oxidation products (3), a claim which has been refuted (6). Several investigators have found that the administration of gluconic acid is followed by the appearance of some unaltered gluconic acid in the urine (5, 6). Apart from the extensive literature relating to 6-phosphogluconic acid, its formation from glucose-6-phosphate, and its further oxidation and decarboxylation, there are numerous reports of enzyme systems derived from various biological sources capable of oxidizing glucose to gluconic acid, without the demonstrated intervention of a phosphorylated intermediate (7-9). Of particular interest to the present discussion is the glucose dehydrogenase of Harrison (10) isolated from mammalian liver, capable of performing the specific oxidation of glucose to gluconic acid in vitro in good yield aerobically in the presence of diphosphopyridine nucleotide (DPN) and methylene blue. The presence of such an enzyme leaves open the possibility that free gluconic acid is formed in the intact liver as a normal oxidative fate of glucose. In the present experiments doubly labeled gluconic acid has been prepared by the mixing of two samples of sodium gluconate, the one labeled with CY4, the other with deuterium. The former was prepared from the starch of bean leaves which had been exposed to CY402, the latter from the.urinary glucose of a diabetic rat receiving DzO. Such doubly labeled material has been injected into normal and phlorhizinized rats and the distribution of isotopes in expired COZ, liver glycogen, urinary gluconate, giucose, and other body constituents has been studied.