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Folate biosynthesis

State Icon Reaction EC-Number Confidence maximal confidence score from EnzymeDetector
7,8-dihydroneopterin + O2 <=> dihydroxanthopterin + formate + glycolaldehyde + H+ 1.13.11.81 7,8-dihydroneopterin oxygenase

4a-hydroxytetrahydrobiopterin <=> dihydrobiopterin + H2O 4.2.1.96 4a-hydroxytetrahydrobiopterin dehydratase

4-(beta-D-ribofuranosyl)aminobenzene-5''-phosphate + 6-hydroxymethyl-7,8-dihydropterin_diphosphate <=> 7,8-dihydropterin-6-ylmethyl-4-(beta-D-ribofuranosyl)aminobenzene_5''-phosphate + diphosphate 2.5.1.105 7,8-dihydropterin-6-yl-methyl-4-(beta-D-ribofuranosyl)aminobenzene 5'-phosphate synthase

7,8-dihydroneopterin <=> 7,8-dihydro-L-monapterin 5.1.99.7 dihydroneopterin triphosphate 2'-epimerase
5.1.99.8 7,8-dihydroneopterin epimerase


tetrahydrobiopterin + NADP+ <=> 6-pyruvoyltetrahydropterin + NADPH + H+ 1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)

4-hydroxybenzoate + 5-phospho-alpha-D-ribose_1-diphosphate + H+ <=> 4-(beta-D-ribofuranosyl)hydroxybenzene_5''-phosphate + CO2 + diphosphate 2.4.2.54 beta-ribofuranosylphenol 5'-phosphate synthase

7,8-dihydrofolate + NAD+ <=> folate + NADH + H+ 1.5.1.3 dihydrofolate reductase

7,8-Dihydroneopterin_3''-triphosphate + H2O <=> 2,5-Diamino-6-(5''-triphosphoryl-3'',4''-trihydroxy-2''-oxopentyl)-amino-4-oxopyrimidine 3.5.4.16 GTP cyclohydrolase I

5,6,7,8-tetrahydromethanopterin + NADP+ <=> 7,8-dihydromethanopterin + NADPH + H+ 1.5.1.47 dihydromethanopterin reductase [NAD(P)+]

6-hydroxymethyl-7,8-dihydropterin_diphosphate + 4-Aminobenzoic_acid <=> 7,8-dihydropteroate + diphosphate 2.5.1.15 dihydropteroate synthase

tetrahydrobiopterin + NAD+ <=> (6R)-L-erythro-6,7-dihydrobiopterin + NADH + H+ 1.5.1.34 6,7-dihydropteridine reductase

tetrahydrofolate + H2O <=> tetrahydrofolate + L-glutamate 3.4.19.9 folate gamma-glutamyl hydrolase

Formamidopyrimidine_nucleoside_triphosphate + H2O <=> 2,5-diaminopyrimidine_nucleoside_triphosphate + formate 3.5.4.16 GTP cyclohydrolase I

pre-queuine_1 + NADP+ <=> 7-cyano-7-carbaguanine + NADPH + H+ 1.7.1.13 preQ1 synthase

cyclic_pyranopterin_phosphate + 2 Thiocarboxy-[sulfur-carrier_protein] <=> molybdopterin + 2 Sulfur-carrier_protein 2.8.1.12 molybdopterin synthase

L-tryptophan + tetrahydrobiopterin + O2 <=> 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin 1.14.16.1 phenylalanine 4-monooxygenase
1.14.16.4 tryptophan 5-monooxygenase


7-carboxy-7-carbaguanine + NH3 + ATP <=> H+ + 7-cyano-7-carbaguanine + ADP + phosphate + H2O 6.3.4.20 7-cyano-7-deazaguanine synthase

5,6,7,8-tetrahydromethanopterin + acceptor <=> 7,8-dihydromethanopterin + reduced_acceptor 1.5.99.15 dihydromethanopterin reductase (acceptor)

dihydrobiopterin + NADP+ <=> sepiapterin + NADPH + H+ 1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
1.1.1.184 carbonyl reductase (NADPH)
1.1.1.53 3alpha(or 20beta)-hydroxysteroid dehydrogenase



molybdenum_cofactor + GTP + H+ <=> molybdopterin_guanine_dinucleotide + diphosphate 2.7.7.77 molybdenum cofactor guanylyltransferase

6-(1''-Hydroxy-2''-oxopropyl)-tetrahydropterin + NADP+ <=> 6-pyruvoyltetrahydropterin + NADPH + H+ 1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
1.1.1.213 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)


2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + ATP <=> H+ + 6-hydroxymethyl-7,8-dihydropterin_diphosphate + AMP 2.7.6.3 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase

5,6,7,8-tetrahydromethanopterin + L-glutamate + ATP <=> H+ + tetrahydrosarcinapterin + ADP + phosphate 6.3.2.33 tetrahydrosarcinapterin synthase

7,8-dihydroneopterin_3''-triphosphate + H2O <=> 6-carboxy-5,6,7,8-tetrahydropterin + acetaldehyde + tripolyphosphate + H+ 4.1.2.50 6-carboxytetrahydropterin synthase

1''-hydroxy-2''-oxopropyltetrahydropterin + NADPH <=> tetrahydrobiopterin + NADP+ 1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
1.1.1.21 aldose reductase


7,8-dihydroneopterin_3''-triphosphate <=> 6-pyruvoyltetrahydropterin + tripolyphosphate + H+ 4.2.3.12 6-pyruvoyltetrahydropterin synthase

H+ + 6-carboxy-5,6,7,8-tetrahydropterin <=> 7-carboxy-7-carbaguanine + NH3 4.3.99.3 7-carboxy-7-deazaguanine synthase

7,8-dihydroneopterin_2,3''-cyclic_phosphate + H2O <=> H+ + 7,8-dihydroneopterin_2''-phosphate 3.1.4.56 7,8-dihydroneopterin 2',3'-cyclic phosphate phosphodiesterase

GTP + H2O <=> 7,8-dihydroneopterin_2,3''-cyclic_phosphate + formate + diphosphate + H+ 3.5.4.16 GTP cyclohydrolase I
3.5.4.39 GTP cyclohydrolase IV


(8S)-3,8-cyclo-7,8-dihydroguanosine_5''-triphosphate <=> cyclic_pyranopterin_phosphate + diphosphate 4.6.1.17 cyclic pyranopterin monophosphate synthase

ATP + tetrahydrofolate + L-glutamate <=> ADP + phosphate + 5,6,7,8-tetrahydropteroyl-Glu2 6.3.2.17 tetrahydrofolate synthase

molybdenum_cofactor + CTP + H+ <=> molybdopterin_cytosine_dinucleotide + diphosphate 2.7.7.76 molybdenum cofactor cytidylyltransferase
2.7.7.77 molybdenum cofactor guanylyltransferase


chorismate + L-glutamine <=> 4-amino-4-deoxychorismate + L-glutamate 2.6.1.85 aminodeoxychorismate synthase

tetrahydrobiopterin + NADP+ <=> (6R)-L-erythro-6,7-dihydrobiopterin + NADPH + H+ 1.5.1.3 dihydrofolate reductase
1.5.1.33 pteridine reductase
1.5.1.34 6,7-dihydropteridine reductase



H+ + molybdopterin + ATP <=> adenylyl-molybdopterin + diphosphate 2.7.7.75 molybdopterin adenylyltransferase

7,8-dihydroneopterin_3''-phosphate <=> 2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde_phosphate 4.1.2.59 dihydroneopterin phosphate aldolase

H2O + GTP <=> H+ + diphosphate + 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone_5'-phosphate + formate 3.5.4.25 GTP cyclohydrolase II

4-amino-4-deoxychorismate <=> H+ + 4-Aminobenzoic_acid + pyruvate 4.1.3.38 aminodeoxychorismate lyase

biopterin + NADPH + H+ <=> dihydrobiopterin + NADP+ 1.5.1.33 pteridine reductase

molybdenum_cofactor + L-cysteine + reduced_acceptor <=> MoOS(OH)Dtpp-mP + L-alanine + H2O + acceptor 2.8.1.9 molybdenum cofactor sulfurtransferase

7,8-dihydroneopterin <=> glycolaldehyde + 2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine 4.1.2.25 dihydroneopterin aldolase

L-tyrosine + tetrahydrobiopterin + O2 <=> L-Dopa + 4a-hydroxytetrahydrobiopterin 1.14.16.2 tyrosine 3-monooxygenase

tetrahydrofolate + L-glutamate + ATP <=> tetrahydrofolate + ADP + phosphate 6.3.2.17 tetrahydrofolate synthase

tetrahydrobiopterin + NADP+ <=> biopterin + NADPH + H+ 1.5.1.33 pteridine reductase

7,8-Dihydroneopterin_3''-triphosphate + 3 H2O <=> 7,8-dihydroneopterin + 3 phosphate 3.1.3.1 alkaline phosphatase

folate + NADPH <=> tetrahydrofolate + NADP+ 1.5.1.3 dihydrofolate reductase
1.5.1.33 pteridine reductase
1.5.1.34 6,7-dihydropteridine reductase



tetrahydro-L-threo-neopterin + NADP+ <=> H+ + 7,8-dihydro-L-monapterin + NADPH 1.5.1.34 6,7-dihydropteridine reductase
1.5.1.50 dihydromonapterin reductase


7,8-dihydroneopterin_2,3''-cyclic_phosphate + H2O <=> H+ + 7,8-dihydroneopterin_3''-phosphate 3.1.4.56 7,8-dihydroneopterin 2',3'-cyclic phosphate phosphodiesterase

S-adenosyl-L-methionine + GTP + reduced_acceptor <=> (8S)-3,8-cyclo-7,8-dihydroguanosine_5''-triphosphate + L-methionine + 5''-deoxyadenosine + acceptor + H+ 4.1.99.22 GTP 3',8-cyclase

tetrahydrobiopterin + NADP+ <=> (6R)-L-erythro-6,7-dihydrobiopterin + NADPH + H+ 1.5.1.3 dihydrofolate reductase
1.5.1.33 pteridine reductase
1.5.1.34 6,7-dihydropteridine reductase



(6R)-L-erythro-6,7-dihydrobiopterin <=> dihydrobiopterin not assigned

adenylyl-molybdopterin + molybdate + H+ <=> molybdenum_cofactor + AMP + H2O 2.10.1.1 molybdopterin molybdotransferase

7,8-dihydroneopterin_3''-triphosphate <=> 2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde_triphosphate 4.1.2.60 dihydroneopterin triphosphate aldolase

1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADPH + H+ <=> tetrahydrobiopterin + NADP+ 1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)

2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone_5'-phosphate <=> 7,8-dihydroneopterin_3''-phosphate + H2O 4.2.1.160 2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one isomerase/dehydratase

7,8-dihydroneopterin_3''-triphosphate + H2O <=> H+ + 7,8-dihydroneopterin_3''-phosphate + diphosphate 3.6.1.67 dihydroneopterin triphosphate diphosphatase

7,8-dihydroneopterin_3''-phosphate + H2O <=> 7,8-dihydroneopterin + phosphate 3.6.1

7,8-dihydroneopterin_3''-triphosphate <=> 7,8-dihydromonapterin_3'-triphosphate 5.1.99.7 dihydroneopterin triphosphate 2'-epimerase
5.1.99.8 7,8-dihydroneopterin epimerase


7,8-dihydrofolate + NADH + H+ <=> tetrahydrofolate + NAD+ 1.5.1.3 dihydrofolate reductase

pyrimidodiazepine + GSSG + H2O <=> 6-pyruvoyltetrahydropterin + glutathione 1.5.4.1 pyrimidodiazepine synthase

L-threo-tetrahydrobiopterin + 2 NADP+ <=> 6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+ 1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
1.1.1.325 sepiapterin reductase (L-threo-7,8-dihydrobiopterin forming)


tetrahydrofolate + NADP+ <=> 7,8-dihydrofolate + NADPH + H+ 1.5.1.3 dihydrofolate reductase
1.5.1.33 pteridine reductase
1.5.1.34 6,7-dihydropteridine reductase
1.5.1.50 dihydromonapterin reductase




7,8-dihydroneopterin + acceptor <=> neopterin + reduced_acceptor not assigned

GTP + H2O <=> Formamidopyrimidine_nucleoside_triphosphate 3.5.4.16 GTP cyclohydrolase I

1'-oxo-2'-L-hydroxypropyl-tetrahydropterin <=> sepiapterin not assigned

2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + 4-Aminobenzoic_acid <=> 7,8-dihydropteroate + H2O 2.5.1
2.5.1.15 dihydropteroate synthase


7,8-dihydrofolate + NADP+ <=> folate + NADPH + H+ 1.5.1.3 dihydrofolate reductase
1.5.1.33 pteridine reductase


1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+ <=> 6-pyruvoyltetrahydropterin + NADPH + H+ 1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
1.1.1.184 carbonyl reductase (NADPH)
1.1.1.21 aldose reductase
1.1.1.220 6-pyruvoyltetrahydropterin 2'-reductase




L-phenylalanine + tetrahydrobiopterin + O2 <=> L-tyrosine + 4a-hydroxytetrahydrobiopterin 1.14.16.1 phenylalanine 4-monooxygenase

L-glutamate + 7,8-dihydropteroate + ATP <=> H+ + 7,8-dihydrofolate + phosphate + ADP 6.3.2.12 dihydrofolate synthase
6.3.2.17 tetrahydrofolate synthase


2,5-diaminopyrimidine_nucleoside_triphosphate <=> 2,5-Diamino-6-(5''-triphosphoryl-3'',4''-trihydroxy-2''-oxopentyl)-amino-4-oxopyrimidine 3.5.4.16 GTP cyclohydrolase I

folate + NADH <=> tetrahydrofolate + NAD+ 1.5.1.3 dihydrofolate reductase
1.5.1.34 6,7-dihydropteridine reductase


Visualization of the pathway