No, I guess they're saying, in those two articles that I cited in my previous posting, that tetrahydrobiopterin (BH4) can be reduced by either/both methylenetetrahydrofolate reductase and dihydrofolate reductase. I can't bring myself to read through them really carefully right now. There's lots of research showing that methylfolate or folate can influence the cellular redox state and the ratio of oxidized to reduced glutathione, and that could influence BH4 regeneration more indirectly than the actions of those folate-derived-cofactor-dependent enzymes may.
I'm not saying there isn't an effect of reduced folates on BH4 regeneration, but it's not clear to me that those effects would occur because BH4 would be more efficiently regenerated, merely because of the presence of an excess of reduced folates or merely by virtue of the capacity, in vitro, of DHF and methylenetetrahydrofolate reductases to reduce BH4. Vitamin C, for example, *can* reduce BH4, too, but vitamin C isn't likely, in my opinion, to produce effects that resemble those of methylfolate. The effects of methylfolate on endothelial nitric oxide synthase are really strong, and I'll try to find, at some point, this one article that shows those effects. Endothelial nitric oxide synthase (and not just tyrosine and tryptophan hydroxylases) also requires BH4 as a cofactor, and the BH4 regeneration/substitution concept has been suggested, by researchers, as a mechanism that would account for the vasodilatory effects of reduced folates. But I think that many of the effects of reduced folates can be explained in terms of the effects of folate-derived cofactors acting as substrates or allosteric activators/inhibitors of folate-cofactor-dependent enzymes.
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