Abstract
Riboflavin has been suggested to act with folate to lower homocysteine (Hcy). However, these interactions may differ among the several known forms of folate. Therefore, we examined the effects of riboflavin interactions with 5-methyltetrahydrofolate (5-MTHF) and tetrahydrofolate (THF) on changes in Hcy and folate derivative levels, under conditions with and without methionine addition. Rat hepatocytes were cultured for 48 hours in medium with or without 2.64 μM riboflavin addition, under the following conditions: 1) without the addition of either methionine or folate; 2) with addition of 2 μM folate derivatives [(A): 5-MTHF, (B): THF]; 3) with addition of both 5 mM methionine and 2 μM folate derivatives [(A): 5-MTHF, (B): THF]. The supernatants were collected at 0, 24, and 48 hours for Hcy and folate derivative measurements. The Hcy lowering effect of 5-MTHF, as well as inhibition of 5-MTHF reduction and THF elevation, appeared to be enhanced by riboflavin addition. THF addition did not lower the Hcy level, regardless of the presence of riboflavin and/or methionine, while THF and 5,10-methenyl THF levels were maintained. Further examination is needed to elucidate the interactive effects of riboflavin and folate derivatives on Hcy and folate metabolism.
Highlights
Folate plays an important role in the remethylation of homocysteine (Hcy), and the synthesis of thymidylate and purine which are precursors for DNA and RNA synthesis [1]
We examined the effects of riboflavin interactions with 5-MTHF and THF on changes in Hcy, 5MTHF, THF and 5,10-methenyl THF levels in rat hepatocytes, under conditions with and without methionine addition
The 5,10-methenyl THF level was increased at 24 hours followed by a decrease at 48 hours in the medium with only 5-MTHF added, while higher levels were maintained by riboflavin addition (p < 0.01) (Figure 3(A))
Summary
Folate plays an important role in the remethylation of homocysteine (Hcy), and the synthesis of thymidylate and purine which are precursors for DNA and RNA synthesis [1]. Dietary folate is generally reduced to tetrahydrofolate (THF) and metabolized to 5-methyltetrahydrofolate (5-MTHF) via 5, 10-methylenetetrahydrofolate reductase (MTHFR) which is a flavoprotein enzyme requiring a flavin adenine dinucleotide (FAD), a derivative of riboflavin, as its coenzyme. 5-MTHF is converted back into THF in parallel with the conversion of Hcy to methionine. A former study examining the effect of riboflavin status on the interaction between the MTHFR TT genotype and Hcy levels in healthy subjects suggested that those with the TT genotype are sensitive to riboflavin status [2]. The Hcy lowering effect of riboflavin [3] and an inverse association between plasma Hcy and plasma riboflavin levels [4] were reported in subjects with the MTHFR TT genotype. Riboflavin would be expected to enhance the Hcy-lowering effect of folate
Published Version (Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have