Studies on the operation of the tricarboxylic acid cycle in scurvy.

Dickmann and Cloutier (1) observed that aconitase is stabilized and activated by ferrous iron and reducing agents such as ascorbic acid or cysteine. This led Takeda and Hara (2) to study the urinary excretion of citric acid and ketone bodies in scorbutic and oc,oc’-dipyridyl-injected guinea pigs after the animals were fed butyrate. These animals excreted increased amounts of citric acid and ketone bodies, possibly attributable to a decline of the ferrous iron concentration with subsequent decrease in aconitase activity. Banerjee et al. (3) observed increased tissue contents of citric, malic, and lactic acids in scorbutic guinea pigs and indicated a possible derangement in their metabolism through the tricarboxylic acid cycle. They observed, however, that the above defects were corrected when guinea pigs received daily injections of a small dose of insulin along with the scorbutogenie diet. Whereas the Japanese workers (2) considered that the decreased aconitase activity was a direct result of the lack of ascorbic acid which maintains the prosthetic Fe++ of the enzyme in the reduced state, Banerjee et al. (3) pointed out that the defect in citric acid metabolism in scurvy might be due as well to insulin insufficiency associated with scurvy (4). The present investigation was undertaken to study the urinary excretions of ketone bodies, citric acid, and malic acid in normal, scorbutic, insulintreated scorbutic, and Fe++ and cysteine-treated scorbutic guinea pigs after the feeding of butyrate.