EFFECT OF CHRONIC CHOLINE DEFICIENCY IN RATS ON LIVER FOLATE CONTENT AND DISTRIBUTION

We have previously reported that folate and choline metabolism are interrelated. Total folate concentration was significantly diminished (31 %) when rats were fed a choline-deficient diet for 2 weeks. Distribution among species of folates (differing in pteridine ring structure and/or in the number of glutamic acid residues) was not altered by this short-term dietary deficiency. In the present study we analyzed folate content and distribution in livers after 12 months on a choline-deficient diet. We found that this long-term deficiency did not significantly alter the total folate concentration in liver, however there was a significant difference between the control and deficient groups in the distribution of folate species. Whereas the major folates in the livers of control rats consisted of penta- and hexaglutamyl derivatives, those from the livers of the choline-deficient group were of longer chain lengths including hepta- and octaglutamyl derivatives. It is believed that chain elongation of the glutamate residues reflects, among other things, increased residence time of the folate molecule in the liver. A plausible interpretation of the previous and the present studies is that choline deprivation interferes with the assimilation of newly acquired folate by the hepatic tissue. Initially, during choline deprivation hepatic folate losses due to normal turnover were not promptly replenished, hence, we observed a decrease in folate level. However, when the period of choline deficiency was extended, impairment in the assimilation of folate was probably compensated for by minimizing folate losses by decreasing folate turnover rates. Hence, we observed an elongation of the glutamate ends of folate molecules.