According to StatPearls, synthetic folic acid — as an artificial dietary supplement — needs to be converted into the active form tetrahydrofolate (THF) by dihydrofolate reductase.

In the cells, folic acid is reduced to THF, a biologically active form, in a two-step process that requires two molecules of NADPH and the enzyme dihydrofolate reductase (DHFR).

But naturally occurring folates — as natural constituents of the diet or derived from intestinal flora — are derivatives of tetrahydrofolate, (the active form), so the human body doesn’t need to convert them using dihydrofolate reductase.

If this is the case, why do humans have the enzyme dihydrofolate reductase?

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    $\begingroup$ Welcome to SE Biology. We find it useful if posters can support their suppositions (in this case "from what I understand") by sources, either text books or online articles. Then we can check if they have perhaps misinterpreted them. Second, we expect posters to show a little research. Have you checked what readily available web sources such as Wikipedia say about DHFR? Also notice that @user438383 has kindly corrected your spelling. However you can do that yourself by writing out your question in a word processor and switching the language preference to English. $\endgroup$
    – David
    Apr 10, 2022 at 10:11
  • $\begingroup$ I have now cited a source and clarified your question, which initially I had difficulty in understanding. Let me know if I have changed your meaning in any way. $\endgroup$
    – David
    Apr 10, 2022 at 10:32
  • $\begingroup$ Thank you @David, that's exactly what I meant. English is not my native language. $\endgroup$
    – toxicodz
    Apr 10, 2022 at 10:38

1 Answer 1


The poster’s assumption that the sole role of dihydrofolate reductase (DHFR) is to convert folic acid to tetrahydrofolate is incorrect. The enzyme is important in at least two metabolic pathways in mammals — the degradation of phenylalanine and the synthesis of thymidine.

Phenylalanine degradation

The degradation of phenylalanine to tyrosine requires tetrahydrobiopterin:

degradation of Phe to Tyr

Tetrahydrobiopterin is synthesized de novo in mammals, the last stage being the reduction of dihydrobiopterin catalysed by dihydrofolate reductase:

Tetrahydrobiopterin synthesis

[Sources: Berg et al. Biochemistry 5e (2002) Ch.28]

Thymidylate synthesis

Thymidine triphosphate (dTPP) is an essential DNA precursor, and is derived from thymidylate (dTMP). This latter is formed by the methylation of dUMP using N5,N10-methylenetetrahydrofolate, which itself is converted to dihydrofolate. This must be reduced to tetrahydrofolate in a reaction catalysed by dihydrofolate reductase in order to regenerate the methylenetetrahydrofolate:

dTMP synthesis cycle

[Source: Berg et al. Biochemistry 5e (2002) Ch.25]


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