Metabolism of Pteroylglutamic Acid and Liver Levels of Nucleic Acids

Abstract

Young rats were offered diets differing in quality and quantity of protein. Feeding of low-protein or protein-free diets or of diets containing nutritionally inferior proteins led to a decreased liver content of folic acid (FA) and citrovorum factor (CF), the level of CF being more depressed than that of FA. Intraperitoneal injection of pteroylglutamic acid 24 hours before examination caused a smaller rise of both FA and CF in deficient rats than in well-fed controls. Supplementation of a low-protein diet with vitamin B12 was without effect upon FA and CF. It is concluded that protein deficiency impairs the ability of the liver to store FA and to convert it into its biologically active form, CF. Liver concentrations of RNA per unit body weight decreased, whereas DNA increased as a result of decreasing the dietary protein. Supplementation with vitamin B12 had no influence upon RNA and DNA levels. Diets containing proteins of low biological value increased liver DNA; supplementation of these diets with the lacking amino acids diminished DNA concentration. Comparison of livers from rats deprived of protein for one and three weeks, respectively, revealed that the latter contained less FA and CF but more nucleic acids per unit body weight. Refeeding a full diet following a period of protein depletion increased liver FA, CF and RNA, the level of DNA remaining unchanged. Administration of aminopterin during the repletion period increased FA and RNA, but not CF and DNA. Incorporation of succinylsulfathiazol into the diet of normal rats significantly depressed the liver concentration of FA. The addition of aminopterin induced a significant decrease of CF. Sulfa treatment had no effect on liver nucleic acids, whereas aminopterin raised the level of RNA per unit of body weight. These results are consistent with the view of the existence in the rat liver of an alternative pathway of nucleic acid synthesis, independent of either FA or CF.