Enzymatic Studies on Pyridoxine Metabolism

II) The Influence of Fat and Fatty Acid Administration upon Pyridoxine Metabolism

Abstract

Kotake et al. observed that when tryptophan was given to rats fed on a high fat diet or administered with a large dose of various fatty acids, there was a remarkable increase in urinary xanthurenic acid excretion. Charconnet-Harding et al. also reported the increased excretion of some tryptophan metabolites including xanthurenic acid in the urine of rats fed on a vitamin B₂ deficient diet. It was agreed in several workers that the abnormal increase of xanthurenic acid excretion in urine was due to vitamin B₆ deficiency. Thus, a close relationship between the roles of vitamins B₂ and B₆ in tryptophan metabolism could be easily inferred. However, no definite explanation could be given to this metabolism.
According to recent reports of Ichihara et al., in mammalian tissues pyridoxal phosphate is formed from pyridoxine via pyridoxine phosphate and pyridoxine phosphate oxidase is a flavoprotein.
In the present works it was examined on the effect of a high fat diet and fatty acid administration on the activity of pyridoxine phosphate oxidase and other enzymes concerned with pyridoxal phosphate formation in rat liver in an effort to clarify the mechanism of the effect of fatty acids. The liver pyridoxal phosphate content and pyridoxine phosphate oxidase activity of rats fed on a high fat diet were determined weekly. They were found to decrease gradually. The change in pyridoxine phosphate oxidase activity seemed to precede that of the pyridoxal phosphate content. This suggests that pyridoxal phosphate formation decreased as a consequence of decreased pyridoxine phosphate oxidase activity. Those depressions both of liver pyridoxal phosphate content and the pyridoxine phosphate oxidase activity were prevented with FMN administration.
Next, the liver pyridoxal phosphate content and pyridoxine phosphate oxidase activity of rats administered oral with various fatty acids were measured and also decreased.
After oral administration of sodium butyrate, the variation of liver pyridoxal phosphate content and pyridoxine phosphate oxidase activity with time investigated, both indicated parallel variation and later returned to normal levels. As in the case of fat feeding, the effect of fatty acids administration was prevented with simultaneous injection of riboflavin.
Also tne activity of xanthine oxidase, a flavine enzyme, was found to be depressed under similar conditions, futhermore addition of FAD in vitro restored the depressed xanthine oxidase activity. Those findings emphasize the fact that fatty acid administration causes a relative vitamin B₂ deficiency.