Folate-homocysteine interrelations: Potential new markers of folate status

We report a transient drop in plasma Hey and Cys following a single oral dose of PteGlu. The thiol change was concomitant with both the peak plasma 5CH(3)H(4)PteGlu1 level (by HPLC) and the maximum plasma Lactobacillus casei activity which reflects absorption of unmodified PteGlu. The significant reciprocal association of Hey with radioassay RBC folate (r = -0.28, 99% CI -0.48, -0.05, P = 0.0016), serum folate (r = -0.37, 99% CI -0.56, -16, P = 0.0001), and vitamin B-12 (r = -0.42, 99% CI -0.59, -21, P = 0.0001) is shown and reflects the long-term nutritional effect of B vitamins on this important, potentially atherogenic thiol. These are now well-established associations. We extend the potential for investigation of folate metabolism in health and disease by evaluating a range of new folate indices which are based on erythrocyte coenzymes. These have been looked at independently and in association with established parameters. Erythrocyte methylfolates (mono- to hexaglutamate-5CH(3)H(4)PteGlu(1-6)), formylfolates (tri-to pentaglutamate-5CHOH(4)PteGlu(3-5)),formiminotetrahydrofolate (formiminoH(4)PteGlu(1)), unsubstituted tetrahydrofolate (H(4)PteGlu(1)), andpara-aminobenzoylglutamate (P-ABG) have been measured by HPLC with fluorescence detection. A positive linear association exists between (i) H(4)PteGlu(1) and radioassay RBC folate (r = 0.50, 99% CI 0.07, 0.77, P = 0.0036), and (ii) H(4)PteGlu(1) and tetraglutamates of both formyland methylfolate (r = 0.52, 99% CI 0.10, 0.78, P = 0.0022, and r = 0.56, 99% CI 0.15, 0.80, P = 0.0009, respectively). Since, in addition, a reciprocal linear association exists between Hey and tetraglutamyl formylfolate (r = -0.41, 99% CI -0.73, 0.05, P = 0.0206), erythrocyte tetraglutamates may be a good reflection of the bodies' active coenzyme pools. Pentaglutamyl formylfolate, the longest oligo-gamma-glutamyl chain form of this coenzyme may be a good indicator of folate depletion. The abundance of this coenzyme both increases with increasing Hcy (r = 0.55, 99% CI 0.13, 0.80, P = 0.0014) and increases as H(4)PteGlu(1), the principle folate congener, decreases (r = -0.59, 99% CI -0.82, -0.20, P = 0.0004). Furthermore, the apparent equilibrium between substrate (5CH(3)H(4)PteGlu(1)) and product (H(4)PteGlu(1)) of methionine synthase is significantly associated with the abundance of 5CHOH(4)PteGlu(5) (r = -0.53, 99% CI -0.79, -0.11, P = 0.0018). This suggests that low methionine synthase activity for whatever reason (metabolic or dietary) may lead to an increase in the relative abundance of 5CHOH(4)PteGlu(5). Like 5CHOH(4)PteGlu(5), evidence is given that 5CH(3)H(4)PteGlu(6), the longest oligo-gamma-glutamyl chain form of this particular coenzyme pool, may also be a good indicator of folate depletion. This is shown by a change in the relative proportion of erythrocyte methylfolate polyglutamates following supplementation with 400 mu g/day PteGlu. Short-chain polyglutamates of methylfolate (5CH(3)H(4)PteGlu(1)-->5CH(3)H(4)PteGlu(4)) increase in proportion to the total methylfolate pool, while long-chain polyglutamates of methylfolate (5CH(3)H(4)PteGlu(5) and particularly 5CH(3)H(4)PteGlu(6)) decrease in their relative abundance. (C) 1999Academic Press.