Relationship of the deposition of folic and folinic acids to choline oxidase of isolated mitochondria.

In several recent publications (14) it has been reported that dietary aminopterin produces a marked decrease in rat liver choline oxidase activity as measured by the whole homogenate technique. A simple folic acid deficiency, however, has been shown to produce only slight changes in the activity of this enzyme (5). It was probable that a simple folic acid deficiency did not deplete the tissues of folic (and folinic) acid to a great enough extent to produce much change in the activity of the whole homogenate. If only minute amounts of a folic acid cofactor were needed by the enzyme, a whole liver homogenate, even from deficient animals, might contain enough of the cofactor to maintain the normal activity of the enzyme. The choline oxidase system of rat liver has been shown to be located in the mitochondrial fraction of liver (6-S). Therefore, the authors felt that, if the mitochondria were isolated, washed, and thus freed of extraneous folic acid, folinic acid, or cofactor containing either of these in bound form, the effects of a simple folic acid deficiency could be demonstrated more clearly. In the present investigation not only the effect of a simple folic acid deficiency on the choline oxidase of isolated mitochondria has been studied, but also a comparison has been made with the effects on the mitochondrial activity of the enzyme produced by feeding aminopterin to rats. In order to complement the enzyme results, and to study the correlation of the eneyme activity with folic acid and folinic acid’ concentration in the tissues, all of the samples used for the enzyme determinations were assayed microbiologically for both folic acid and folinic acid. In the course of these