Modulation of Pteroylpolyglutamate Concentration and Length in Response to Altered Folate Nutrition in a Comprehensive Range of Rat Tissues

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Abstract
For a range of rat tissue extracts, the concentrations of total folates and of short-chain pteroylpolyglutamates were assayed by Lactobacillus casel with and without conjugase treatment, respectively, and the concentration and chain length of H4Pte-Glnn and 5,10-CH2-H4PteGlnn together were assayed after binding to thymidylate synthase and tritiated fluorodeoxyuridylate. For rats fed a nonpurified diet and consuming 26 µg of folic acid daily, the respective concentrations of these total folates, short-chain folates and thymidylate synthase bindable folates were, in nmol/g, 10.2, 2.5 and 3.5 in liver, 3.9, 1.8 and 2.0 in kidney, 4.2, 1.2 and 1.0 in bone marrow, 2.3, 0.6 and 0.2 in adrenal, 2.1, 0.3 and 0.5 in spleen, 2.1, 0.9 and 0.8 in jejunal smooth muscle, 1.2, 0.9 and 0.2 in jejunal mucosa, 1.0, 0.3 and 0.6 in testis, 0.7, 0.1 and 0.2 in heart, 0.3, 0.1 and 0.1 in skeletal muscle, 0.5, 0.1 and 0.3 in brain and 0.7, 0.002 and 0 in erythrocytes. The predominant pteroylpolyglutamate chain length was 6 residues in all tissues except kidney, jejunal mucosa, skeletal muscle and brain, in which the value was 5 residues. A folate-deficient diet (30 ng/d) fed for 3 wk resulted in a depression in the total folate concentration of all tissues (except brain); the depression was generally greater for short-chain than for long-chain folates and was accompanied by a length-ening of the pteroylpolyglutamate chain. Opposite results followed folate excess of 4 to 5.4 mg/d. The fractional change in the folate concentration of the individual tissues, following perturbation of dietary folate, did not vary greatly among tissues. These results are interpreted as evidence that folylpolyglutamate synthetase operates in most tissues to increase chain length in periods of folate deficiency and that there is no particular tissue whose pool of folates constitutes a metabolically inactive store.