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Human Metabolome Database Version 2.5

 

Showing metabocard for 5-Methyltetrahydrofolic acid (HMDB01396)

Legend: metabolite field enzyme field

Version 2.5
Creation Date 2005-11-16 15:48:42
Update Date 2009-05-05 20:58:45
Accession Number HMDB01396
Secondary Accession Numbers Not Available
Common Name 5-Methyltetrahydrofolic acid
Description 5 methyltetrahydrofolic acid (5-MTHF) is the most biologically active form of the B-vitamin folic acid, also known generically as folate. 5-MTHF functions, in concert with vitamin B12, as a methyl-group donor involved in the conversion of the amino acid homocysteine to methionine. Methyl (CH3) group donation is vital to many bodily processes, including serotonin, melatonin, and DNA synthesis. Therapeutically, 5-MTHF is instrumental in reducing homocysteine levels, preventing neural tube defects, and improving vascular endothelial function. Research on folate supplementation suggests it plays a key role in preventing cervical dysplasia and protecting against neoplasia in ulcerative colitis. Folic acid also shows promise as part of a nutritional protocol to treat vitiligo, and may reduce inflammation of the gingiva. Furthermore, certain neurological, cognitive, and psychiatric presentations may be secondary to folate deficiency. Such presentations include depression, peripheral neuropathy, myelopathy, restless legs syndrome, insomnia, dementia, forgetfulness, irritability, endogenous depression, organic psychosis, and schizophrenia-like syndromes. After ingestion, the process of conversion of folic acid to the metabolically active coenzyme forms is relatively complex. Synthesis of the active forms of folic acid requires several enzymes, adequate liver and intestinal function, and adequate supplies of riboflavin (B2), niacin (B3), pyridoxine (B6), zinc, vitamin C, and serine. After formation of the coenzyme forms of the vitamin in the liver, these metabolically active compounds are secreted into the small intestine with bile (the folate enterohepatic cycle), where they are reabsorbed and distributed to tissues throughout the body. Human pharmacokinetic studies indicate folic acid has high bioavailability, with large oral doses of folic acid substantially raising plasma levels in healthy subjects in a time and dose dependent manner. Red blood cells (RBCs) appear to be the storage depot for folic acid, as RBC levels remain elevated for periods in excess of 40 days following discontinuation of supplementation. Folic acid is poorly transported to the brain and rapidly cleared from the central nervous system. The primary methods of elimination of absorbed folic acid are fecal (through bile) and urinary. Despite the biochemical complexity of this process, evidence suggests oral supplementation with folic acid increases the body's pool of 5-MTHF in healthy individuals. However, enzyme defects, mal-absorption, digestive system pathology, and liver disease can result in impaired ability to activate folic acid. In fact, some individuals have a severe congenital deficiency of the enzyme Methyl tetrahydrofolate reductase (5-MTHFR), which is needed to convert folic acid to 5-MTHF. Milder forms of this enzyme defect likely interact with dietary folate status to determine risk for some disease conditions. In individuals with a genetic defect of this enzyme (whether mild or severe), supplementation with 5- MTHF might be preferable to folic acid supplementation. (PMID: 17176169)
Synonyms
  1. 5-Methyl tetrahydrofolate
  2. 5-Methyltetrahydropteroylglutamate
  3. 5-methyl-5,6,7,8-tetrahydrofolate
  4. 5-methyl-tetrahydrofolate
  5. Methyl folate
  6. N( 5)-Methyltetrahydrofolate
  7. N-(4-(((2-amino-1,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-Glutamate
  8. N-(4-(((2-amino-1,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-Glutamic acid
  9. N-(5-methyl-5,6,7,8-tetrahydropteroyl)-L-glutamate
  10. N-(5-methyl-5,6,7,8-tetrahydropteroyl)-L-glutamic acid
  11. N5-Methyl-tetrahydrofolate
  12. N5-Methyl-tetrahydrofolic acid
  13. N5-methyltetrahydropteroyl mono-L-glutamate
  14. [(6S)-5-methyl-5,6,7,8-tetrahydropteroyl]glutamate
  15. methyl-tetrahydrofolate
  16. 5-Methyltetrahydrofolate
  17. N5-methyltetrahydrofolate
Chemical IUPAC Name 2-[4-[(2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]aminopentanedioic acid
Chemical Formula C20H25N7O6
Chemical Structure Structure
Chemical Taxonomy
Kingdom
  • Organic
Super Class
  • Heterocyclic molecules
Class
  • Pterins
Sub Class
  • Tetrahydro-pterins
Family
  • Mammalian Metabolite
Species
  • primary amine
  • primary aromatic amine
  • secondary amine
  • secondary aliphatic/aromatic amine (alkylarylamine)
  • tertiary amine
  • tertiary aliphatic/aromatic amine (alkylarylamine)
  • carboxylic acid
  • secondary carboxylic acid amide
  • oxo(het)arene
  • aromatic compound
  • heterocyclic compound
Biofunction
  • Component of Methionine metabolism
Application
—
Source
  • Endogenous
Average Molecular Weight 459.456
Monoisotopic Molecular Weight 459.186646
Isomeric SMILES CN1C(CNC2=CC=C(C=C2)C(=O)N[C@H](CCC(O)=O)C(O)=O)CNC2=C1C(=O)NC(N)=N2
Canonical SMILES CN1C(CNC2=CC=C(C=C2)C(=O)NC(CCC(O)=O)C(O)=O)CNC2=C1C(=O)NC(N)=N2
KEGG Compound ID C00440 Link Image
BioCyc ID 5-METHYL-THF Link Image
BiGG ID 34988 Link Image
Wikipedia Link 5-Methyltetrahydrofolate Link Image
NuGOwiki Link HMDB01396 Link Image
Metagene Link HMDB01396 Link Image
METLIN ID 6215 Link Image
PubChem Compound 439234 Link Image
PubChem Substance 3729 Link Image
ChEBI ID 15641 Link Image
CAS Registry Number 134-35-0
InChI Identifier InChI=1/C20H25N7O6/c1-27-12(9-23-16-15(27)18(31)26-20(21)25-16)8-22-11-4-2-10(3-5-11)17(30)24-13(19(32)33)6-7-14(28)29/h2-5,12-13,22H,6-9H2,1H3,(H,24,30)(H,28,29)(H,32,33)(H4,21,23,25,26,31)/t12?,13-/m1/s1
Synthesis Reference Gennari, Federico. Process for producing 5-methyltetrahydrofolic acid and its salts. U.S. (1992), 6 pp.
Melting Point (Experimental) Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 0.34600002 mg/mL [Predicted by ALOGPS] Calculated using ALOGPS
Physiological Charge -2
State Solid
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP/Hydrophobicity -1.26 [Predicted by ALOGPS]; -2.1 [Predicted by PubChem via XLOGP] Calculated using ALOGPS
Material Safety Data Sheet (MSDS) Not Available
MOL File Show
SDF File Show
PDB File Show
2D Structure
3D Structure
Experimental PDB ID Not Available
Experimental 1H NMR Spectrum Not Available
Experimental 13C NMR Spectrum Not Available
Experimental 13C HSQC Spectrum Not Available
Predicted 1H NMR Spectrum Show Image
Show Peaklist
Predicted 13C NMR Spectrum Show Image
Show Peaklist
Mass Spectrum Not Available
Simplified TOCSY Spectrum Not Available
BMRB Spectrum Not Available
Cellular Location
  • Cytoplasm (Predicted from LogP)
  • Extracellular
Biofluid Location
  • Blood
  • Cerebrospinal Fluid
Tissue Location
Tissue References
Placenta —
Concentrations (Normal)
Biofluid Blood
Value 0.3 (0.094-0.7) uM
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
  • Fazili Z, Pfeiffer CM, Zhang M, Jain RB, Koontz D: Influence of 5,10-methylenetetrahydrofolate reductase polymorphism on whole-blood folate concentrations measured by LC-MS/MS, microbiologic assay, and bio-rad radioassay. Clin Chem. 2008 Jan;54(1):197-201. [PubMed Link Image]
Biofluid CSF
Value 0.075 (0.045 - 0.13) uM
Age Adult:>18 yrs old
Sex N/A
Patient information Normal
Comments Not Available
References
  • Ormazabal A, Artuch R, Vilaseca MA, Aracil A, Pineda M: Cerebrospinal fluid concentrations of folate, biogenic amines and pterins in Rett syndrome: treatment with folinic acid. Neuropediatrics. 2005 Dec;36(6):380-5. [PubMed Link Image]
Biofluid CSF
Value 0.12 (0.04-0.20) uM
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
  • Van Hove JL, Lazeyras F, Zeisel SH, Bottiglieri T, Hyland K, Charles HC, Gray L, Jaeken J, Kahler SG: One-methyl group metabolism in non-ketotic hyperglycinaemia: mildly elevated cerebrospinal fluid homocysteine levels. J Inherit Metab Dis. 1998 Dec;21(8):799-811. [PubMed Link Image]
Concentrations (Abnormal)
Biofluid CSF
Value 0.053 (0.02 - 0.09) uM
Age Adult:>18 yrs old
Sex N/A
Condition Rett syndrome
Comments Not Available
References
  • Ormazabal A, Artuch R, Vilaseca MA, Aracil A, Pineda M: Cerebrospinal fluid concentrations of folate, biogenic amines and pterins in Rett syndrome: treatment with folinic acid. Neuropediatrics. 2005 Dec;36(6):380-5. [PubMed Link Image]
Biofluid CSF
Value 0.026 +/- 0.007 uM
Age Children:1-13 yrs old
Sex N/A
Condition AIDS
Comments Neurological complications of HIV infection
References
  • Surtees R, Hyland K, Smith I: Central-nervous-system methyl-group metabolism in children with neurological complications of HIV infection. Lancet. 1990 Mar 17;335(8690):619-21. [PubMed Link Image]
Associated Disorders
Condition References
AIDS
  • Surtees R, Hyland K, Smith I: Central-nervous-system methyl-group metabolism in children with neurological complications of HIV infection. Lancet. 1990 Mar 17;335(8690):619-21. [PubMed Link Image]
Rett syndrome
  • Ormazabal A, Artuch R, Vilaseca MA, Aracil A, Pineda M: Cerebrospinal fluid concentrations of folate, biogenic amines and pterins in Rett syndrome: treatment with folinic acid. Neuropediatrics. 2005 Dec;36(6):380-5. [PubMed Link Image]
OMIM ID
Pathways
Name SMPDB Link KEGG Link
Betaine Metabolism SMP00123 Link Image map00260 Link Image
Folate Metabolism SMP00053 Link Image map00670 Link Image
Methionine Metabolism SMP00033 Link Image map00270 Link Image
General References
  1. Garbis SD, Melse-Boonstra A, West CE, van Breemen RB: Determination of folates in human plasma using hydrophilic interaction chromatography-tandem mass spectrometry. Anal Chem. 2001 Nov 15;73(22):5358-64. [PubMed Link Image]
  2. Ormazabal A, Artuch R, Vilaseca MA, Aracil A, Pineda M: Cerebrospinal fluid concentrations of folate, biogenic amines and pterins in Rett syndrome: treatment with folinic acid. Neuropediatrics. 2005 Dec;36(6):380-5. [PubMed Link Image]
  3. Chladek J, Sispera L, Martinkova J: High-performance liquid chromatographic assay for the determination of 5-methyltetrahydrofolate in human plasma. J Chromatogr B Biomed Sci Appl. 2000 Jul 21;744(2):307-13. [PubMed Link Image]
  4. Prasad PD, Mahesh VB, Leibach FH, Ganapathy V: Functional coupling between a bafilomycin A1-sensitive proton pump and a probenecid-sensitive folate transporter in human placental choriocarcinoma cells. Biochim Biophys Acta. 1994 Jun 30;1222(2):309-14. [PubMed Link Image]
  5. Kim TH, Yang J, Darling PB, O'Connor DL: A large pool of available folate exists in the large intestine of human infants and piglets. J Nutr. 2004 Jun;134(6):1389-94. [PubMed Link Image]
  6. Camilo E, Zimmerman J, Mason JB, Golner B, Russell R, Selhub J, Rosenberg IH: Folate synthesized by bacteria in the human upper small intestine is assimilated by the host. Gastroenterology. 1996 Apr;110(4):991-8. [PubMed Link Image]
  7. Kamen BA, Smith AK: A review of folate receptor alpha cycling and 5-methyltetrahydrofolate accumulation with an emphasis on cell models in vitro. Adv Drug Deliv Rev. 2004 Apr 29;56(8):1085-97. [PubMed Link Image]
  8. Surtees R, Leonard J, Austin S: Association of demyelination with deficiency of cerebrospinal-fluid S-adenosylmethionine in inborn errors of methyl-transfer pathway. Lancet. 1991 Dec 21-28;338(8782-8783):1550-4. [PubMed Link Image]
  9. Surtees R, Hyland K, Smith I: Central-nervous-system methyl-group metabolism in children with neurological complications of HIV infection. Lancet. 1990 Mar 17;335(8690):619-21. [PubMed Link Image]
  10. Evans MI, Duquette DA, Rinaldo P, Bawle E, Rosenblatt DS, Whitty J, Quintero RA, Johnson MP: Modulation of B12 dosage and response in fetal treatment of methylmalonic aciduria (MMA): titration of treatment dose to serum and urine MMA. Fetal Diagn Ther. 1997 Jan-Feb;12(1):21-3. [PubMed Link Image]
  11. Kane MA, Roth E, Raptis G, Schreiber C, Waxman S: Effect of intracellular folate concentration on the modulation of 5-fluorouracil cytotoxicity by the elevation of phosphoribosylpyrophosphate in cultured human KB cells. Cancer Res. 1987 Dec 15;47(24 Pt 1):6444-50. [PubMed Link Image]
  12. Irizarry MC: Biomarkers of Alzheimer disease in plasma. NeuroRx. 2004 Apr;1(2):226-34. [PubMed Link Image]
  13. Van Hove JL, Lazeyras F, Zeisel SH, Bottiglieri T, Hyland K, Charles HC, Gray L, Jaeken J, Kahler SG: One-methyl group metabolism in non-ketotic hyperglycinaemia: mildly elevated cerebrospinal fluid homocysteine levels. J Inherit Metab Dis. 1998 Dec;21(8):799-811. [PubMed Link Image]
  14. Straw JA, Szapary D, Wynn WT: Pharmacokinetics of the diastereoisomers of leucovorin after intravenous and oral administration to normal subjects. Cancer Res. 1984 Jul;44(7):3114-9. [PubMed Link Image]
  15. Wikipedia Link Image
Metabolic Enzymes
  1. Methionine synthase
  2. Methylenetetrahydrofolate reductase
Enzyme 1 [top]
Enzyme 1 ID 5392
Enzyme 1 Name Methionine synthase
Enzyme 1 Synonyms
  1. 5-methyltetrahydrofolate-- homocysteine methyltransferase
  2. Methionine synthase, vitamin-B12 dependent
  3. MS
Enzyme 1 Gene Name MTR
Enzyme 1 Protein Sequence >Methionine synthase 
MSPALQDLSQPEGLKKTLRDEINAILQKRIMVLDGGMGTMIQREKLNEEHFRGQEFKDHA
RPLKGNNDILSITQPDVIYQIHKEYLLAGADIIETNTFSSTSIAQADYGLEHLAYRMNMC
SAGVARKAAEEVTLQTGIKRFVAGALGPTNKTLSVSPSVERPDYRNITFDELVEAYQEQA
KGLLDGGVDILLIETIFDTANAKAALFALQNLFEEKYAPRPIFISGTIVDKSGRTLSGQT
GEGFVISVSHGEPLCIGLNCALGAAEMRPFIEIIGKCTTAYVLCYPNAGLPNTFGDYDET
PSMMAKHLKDFAMDGLVNIVGGCCGSTPDHIREIAEAVKNCKPRVPPATAFEGHMLLSGL
EPFRIGPYTNFVNIGERCNVAGSRKFAKLIMAGNYEEALCVAKVQVEMGAQVLDVNMDDG
MLDGPSAMTRFCNLIASEPDIAKVPLCIDSSNFAVIEAGLKCCQGKCIVNSISLKEGEDD
FLEKARKIKKYGAAMVVMAFDEEGQATETDTKIRVCTRAYHLLVKKLGFNPNDIIFDPNI
LTIGTGMEEHNLYAINFIHATKVIKETLPGARISGGLSNLSFSFRGMEAIREAMHGVFLY
HAIKSGMDMGIVNAGNLPVYDDIHKELLQLCEDLIWNKDPEATEKLLRYAQTQGTGGKKV
IQTDEWRNGPVEERLEYALVKGIEKHIIEDTEEARLNQKKYPRPLNIIEGPLMNGMKIVG
DLFGAGKMFLPQVIKSARVMKKAVGHLIPFMEKEREETRVLNGTVEEEDPYQGTIVLATV
KGDVHDIGKNIVGVVLGCNNFRVIDLGVMTPCDKILKAALDHKADIIGLSGLITPSLDEM
IFVAKEMERLAIRIPLLIGGATTSKTHTAVKIAPRYSAPVIHVLDASKSVVVCSQLLDEN
LKDEYFEEIMEEYEDIRQDHYESLKERRYLPLSQARKSGFQMDWLSEPHPVKPTFIGTQV
FEDYDLQKLVDYIDWKPFFDVWQLRGKYPNRGFPKIFNDKTVGGEARKVYDDAHNMLNTL
ISQKKLRARGVVGFWPAQSIQDDIHLYAEAAVPQAAEPIATFYGLRQQAEKDSASTEPYY
CLSDFIAPLHSGIRDYLGLFAVACFGVEELSKAYEDDGDDYSSIMVKALGDRLAEAFAEE
LHERVRRELWAYCGSEQLDVADLRRLRYKGIRPAPGYPSQPDHTEKLTMWRLADIEQSTG
IRLTESLAMAPASAVSGLYFSNLKSKYFAVGKISKDQVEDYALRKNISVAEVEKWLGPIL
GYDTD
Enzyme 1 Number of Residues 1265
Enzyme 1 Molecular Weight 140529
Enzyme 1 Theoretical pI 5.27
Enzyme 1 GO Classification
Function
  • S-methyltransferase activity
  • binding
  • catalytic activity
  • cation binding
  • cobalamin binding
  • cobalt ion binding
  • dihydropteroate synthase activity
  • homocysteine S-methyltransferase activity
  • ion binding
  • methionine synthase activity
  • methyltransferase activity
  • transferase activity
  • transferase activity, transferring alkyl or aryl (other than methyl) groups
  • transferase activity, transferring one-carbon groups
  • transition metal ion binding
  • vitamin binding
Process
  • amino acid and derivative metabolism
  • amino acid metabolism
  • aromatic compound metabolism
  • cellular metabolism
  • folic acid and derivative biosynthesis
  • folic acid and derivative metabolism
  • metabolism
  • methionine biosynthesis
  • physiological process
  • sulfur amino acid biosynthesis
  • sulfur amino acid metabolism
Component
  • cell
  • intracellular
Enzyme 1 General Function Amino acid transport and metabolism
Enzyme 1 Specific Function Catalyzes the transfer of a methyl group from methyl- cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate
Enzyme 1 Pathways
Enzyme 1 Reactions
  • 5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
Enzyme 1 Pfam Domain Function
Enzyme 1 Signals
  • None
Enzyme 1 Transmembrane Regions
  • None
Enzyme 1 Essentiality Not Available
Enzyme 1 GenBank ID Protein 1923221 Link Image
Enzyme 1 UniProtKB/Swiss-Prot ID Q99707 Link Image
Enzyme 1 UniProtKB/Swiss-Prot Entry Name METH_HUMAN Link Image
Enzyme 1 PDB ID Not Available
Enzyme 1 Cellular Location Not Available
Enzyme 1 Gene Sequence >3798 bp 
ATGTCACCCGCGCTCCAAGACCTGTCGCAACCCGAAGGTCTGAAGAAAACCCTGCGGGAT
GAGATCAATGCCATTCTGCAGAAGAGGATTATGGTGCTGGATGGAGGGATGGGGACCATG
ATCCAGCGGGAGAAGCTAAACGAAGAACACTTCCGAGGTCAGGAATTTAAAGATCATGCC
AGGCCGCTGAAAGGCAACAATGACATTTTAAGTATAACTCAGCCTGATGTCATTTACCAA
ATCCATAAGGAATACTTGCTGGCTGGGGCAGATATCATTGAAACAAATACTTTTAGCAGC
ACTAGTATTGCCCAAGCTGACTATGGCCTTGAACACTTGGCCTACCGGATGAACATGTGC
TCTGCAGGAGTGGCCAGAAAAGCTGCCGAGGAGGTAACTCTCCAGACAGGAATTAAGAGG
TTTGTGGCAGGGGCTCTGGGTCCGACTAATAAGACACTCTCTGTGTCCCCATCTGTGGAA
AGGCCGGATTATAGGAACATCACATTTGATGAGCTTGTTGAAGCATACCAAGAGCAGGCC
AAAGGACTTCTGGATGGCGGGGTTGATATCTTACTCATTGAAACTATTTTTGATACTGCC
AATGCCAAGGCAGCCTTGTTTGCACTCCAAAATCTTTTTGAGGAGAAATATGCTCCCCGG
CCTATCTTTATTTCAGGGACGATCGTTGATAAAAGTGGGCGGACTCTTTCCGGACAGACA
GGAGAGGGATTTGTCATCAGCGTGTCTCATGGAGAACCACTCTGCATTGGATTAAATTGT
GCTTTGGGTGCAGCTGAGATGAGACCTTTTATTGAAATAATTGGAAAATGTACAACAGCC
TATGTCCTCTGTTATCCCAATGCAGGTCTTCCCAACACCTTTGGTGACTATGATGAAACG
CCTTCTATGATGGCCAAGCACCTAAAGGATTTTGCTATGGATGGCTTGGTCAATATAGTT
GGAGGATGCTGTGGGTCAACACCAGATCATATCAGGGAAATTGCTGAAGCTGTGAAAAAT
TGTAAGCCTAGAGTTCCACCTGCCACTGCTTTTGAAGGACATATGTTACTGTCTGGTCTA
GAGCCCTTCAGGATTGGACCGTACACCAACTTTGTTAACATTGGAGAGCGCTGTAATGTT
GCAGGATCAAGGAAGTTTGCTAAACTCATCATGGCAGGAAACTATGAAGAAGCCTTGTGT
GTTGCCAAAGTGCAGGTGGAAATGGGAGCCCAGGTGTTGGATGTCAACATGGATGATGGC
ATGCTAGATGGTCCAAGTGCAATGACCAGATTTTGCAACTTAATTGCTTCCGAGCCAGAC
ATCGCAAAGGTACCTTTGTGCATCGACTCCTCCAATTTTGCTGTGATTGAAGCTGGGTTA
AAGTGCTGCCAAGGGAAGTGCATTGTCAATAGCATTAGTCTGAAGGAAGGAGAGGACGAC
TTCTTGGAGAAGGCCAGGAAGATTAAAAAGTATGGAGCTGCTATGGTGGTCATGGCTTTT
GATGAAGAAGGACAGGCAACAGAAACAGACACAAAAATCAGAGTGTGCACCCGGGCCTAC
CATCTGCTTGTGAAAAAACTGGGCTTTAATCCAAATGACATTATTTTTGACCCTAATATC
CTAACCATTGGGACTGGAATGGAGGAACACAACTTGTATGCCATTAATTTTATCCATGCA
ACAAAAGTCATTAAAGAAACATTACCTGGAGCCAGAATAAGTGGAGGTCTTTCCAACTTG
TCCTTCTCCTTCCGAGGAATGGAAGCCATTCGAGAAGCAATGCATGGGGTTTTCCTTTAC
CATGCAATCAAGTCTGGCATGGACATGGGGATAGTGAATGCTGGAAACCTCCCTGTGTAT
GATGATATCCATAAGGAACTTCTGCAGCTCTGTGAAGATCTCATCTGGAATAAAGACCCT
GAGGCCACTGAGAAGCTCTTACGTTATGCCCAGACTCAAGGCACAGGAGGGAAGAAAGTC
ATTCAGACTGATGAGTGGAGAAATGGCCCTGTCGAAGAACGCCTTGAGTATGCCCTTGTG
AAGGGCATTGAAAAACATATTATTGAGGATACTGAGGAAGCCAGGTTAAACCAAAAAAAA
TATCCCCGACCTCTCAATATAATTGAAGGACCCCTGATGAATGGAATGAAAATTGTTGGT
GATCTTTTTGGAGCTGGAAAAATGTTTCTACCTCAGGTTATAAAGTCAGCCCGGGTTATG
AAGAAGGCTGTTGGCCACCTTATCCCTTTCATGGAAAAAGAAAGAGAAGAAACCAGAGTG
CTTAACGGCACAGTAGAAGAAGAGGACCCTTACCAGGGCACCATCGTGCTGGCCACTGTT
AAAGGCGACGTGCACGACATAGGCAAGAACATAGTTGGAGTAGTCCTTGGCTGCAATAAT
TTCCGAGTTATTGATTTAGGAGTCATGACTCCATGTGATAAGATACTGAAAGCTGCTCTT
GACCACAAAGCAGATATAATTGGCCTGTCAGGACTCATCACTCCTTCCCTGGATGAAATG
ATTTTTGTTGCCAAGGAAATGGAGAGATTAGCTATAAGGATTCCATTGTTGATTGGAGGA
GCAACCACTTCAAAAACCCACACAGCAGTTAAAATAGCTCCGAGATACAGTGCACCTGTA
ATCCATGTCCTGGACGCGTCCAAGAGTGTGGTGGTGTGTTCCCAGCTGTTAGATGAAAAT
CTAAAGGATGAATACTTTGAGGAAATCATGGAAGAATATGAAGATATTAGACAGGACCAT
TATGAGTCTCTCAAGGAGAGGAGATACTTACCCTTAAGTCAAGCCAGAAAAAGTGGTTTC
CAAATGGATTGGCTGTCTGAACCTCACCCAGTGAAGCCCACGTTTATTGGGACCCAGGTC
TTTGAAGACTATGACCTGCAGAAGCTGGTGGACTACATTGACTGGAAGCCTTTCTTTGAT
GTCTGGCAGCTCCGGGGCAAGTACCCGAATCGAGGCTTCCCCAAGATATTTAACGACAAA
ACAGTAGGTGGAGAGGCCAGGAAGGTCTACGATGATGCCCACAATATGCTGAACACACTG
ATTAGTCAAAAGAAACTCCGGGCCCGGGGTGTGGTTGGGTTCTGGCCAGCACAGAGTATC
CAAGACGACATTCACCTGTACGCAGAGGCTGCTGTGCCCCAGGCTGCAGAGCCCATAGCC
ACTTTCTATGGGTTAAGGCAACAGGCTGAGAAGGACTCTGCCAGCACGGAGCCATACTAC
TGCCTCTCAGACTTCATCGCTCCCTTGCATTCTGGCATCCGTGACTACCTGGGCCTGTTT
GCCGTTGCCTGCTTTGGGGTAGAAGAGCTGAGCAAGGCCTATGAGGATGATGGTGACGAC
TACAGCAGCATCATGGTCAAGGCGCTGGGGGACCGGCTGGCAGAGGCCTTTGCAGAAGAG
CTCCATGAAAGAGTTCGCCGAGAACTGTGGGCCTACTGTGGCAGTGAGCAGCTGGACGTC
GCAGACCTGCGAAGGTTGCGGTACAAGGGCATCCGCCCGGCTCCTGGCTACCCCAGCCAG
CCCGACCACACCGAGAAGCTCACCATGTGGAGACTCGCAGACATCGAGCAGTCTACAGGC
ATTAGGTTAACAGAATCATTAGCAATGGCACCTGCTTCAGCAGTCTCAGGCCTCTACTTC
TCCAATTTGAAGTCCAAATATTTTGCTGTGGGGAAGATTTCCAAGGATCAGGTTGAGGAT
TATGCATTGAGGAAGAACATATCTGTGGCTGAGGTTGAGAAATGGCTTGGACCCATTTTG
GGATATGATACAGACTAA
Enzyme 1 GenBank Gene ID U71285 Link Image
Enzyme 1 GeneCard ID MTR Link Image
Enzyme 1 GenAtlas ID MTR Link Image
Enzyme 1 HGNC ID HGNC:7468 Link Image
Enzyme 1 Chromosome Location 1
Enzyme 1 Locus 1q43
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 General References
  1. Leclerc D, Campeau E, Goyette P, Adjalla CE, Christensen B, Ross M, Eydoux P, Rosenblatt DS, Rozen R, Gravel RA: Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders. Hum Mol Genet. 1996 Dec;5(12):1867-74. [PubMed Link Image]
  2. Li YN, Gulati S, Baker PJ, Brody LC, Banerjee R, Kruger WD: Cloning, mapping and RNA analysis of the human methionine synthase gene. Hum Mol Genet. 1996 Dec;5(12):1851-8. [PubMed Link Image]
  3. Chen LH, Liu ML, Hwang HY, Chen LS, Korenberg J, Shane B: Human methionine synthase. cDNA cloning, gene localization, and expression. J Biol Chem. 1997 Feb 7;272(6):3628-34. [PubMed Link Image]
  4. Gulati S, Baker P, Li YN, Fowler B, Kruger W, Brody LC, Banerjee R: Defects in human methionine synthase in cblG patients. Hum Mol Genet. 1996 Dec;5(12):1859-65. [PubMed Link Image]
Enzyme 1 Metabolite References Not Available
Enzyme 2 [top]
Enzyme 2 ID 5420
Enzyme 2 Name Methylenetetrahydrofolate reductase
Enzyme 2 Synonyms Not Available
Enzyme 2 Gene Name MTHFR
Enzyme 2 Protein Sequence >Methylenetetrahydrofolate reductase 
MVNEARGNSSLNPCLEGSASSGSESSKDSSRCSTPGLDPERHERLREKMRRRLESGDKWF
SLEFFPPRTAEGAVNLISRFDRMAAGGPLYIDVTWHPAGDPGSDKETSSMMIASTAVNYC
GLETILHMTCCRQRLEEITGHLHKAKQLGLKNIMALRGDPIGDQWEEEEGGFNYAVDLVK
HIRSEFGDYFDICVAGYPKGHPEAGSFEADLKHLKEKVSAGADFIITQLFFEADTFFRFV
KACTDMGITCPIVPGIFPIQGYHSLRQLVKLSKLEVPQEIKDVIEPIKDNDAAIRNYGIE
LAVSLCQELLASGLVPGLHFYTLNREMATTEVLKRLGMWTEDPRRPLPWALSAHPKRREE
DVRPIFWASRPKSYIYRTQEWDEFPNGRWGNSSSPAFGELKDYYLFYLKSKSPKEELLKM
WGEELTSEESVFEVFVLYLSGEPNRNGHKVTCLPWNDEPLAAETSLLKEELLRVNRQGIL
TINSQPNINGKPSSDPIVGWGPSGGYVFQKAYLEFFTSRETAEALLQVLKKYELRVNYHL
VNVKGENITNAPELQPNAVTWGIFPGREIIQPTVVDPVSFMFWKDEAFALWIERWGKLYE
EESPSRTIIQYIHDNYFLVNLVDNDFPLDNCLWQVVEDTLELLNRPTQNARETEAP
Enzyme 2 Number of Residues 656
Enzyme 2 Molecular Weight 74597
Enzyme 2 Theoretical pI 5.00
Enzyme 2 GO Classification
Function
  • catalytic activity
  • methylenetetrahydrofolate reductase (NADPH) activity
  • methylenetetrahydrofolate reductase (NADPH) activity
  • oxidoreductase activity
  • oxidoreductase activity, acting on the CH-NH group of donors
  • oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor
Process
  • amino acid and derivative metabolism
  • amino acid metabolism
  • cellular metabolism
  • metabolism
  • methionine metabolism
  • physiological process
  • sulfur amino acid metabolism
Component
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Enzyme 2 General Function Amino acid transport and metabolism
Enzyme 2 Specific Function Catalyzes the conversion of 5,10- methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co- substrate for homocysteine remethylation to methionine
Enzyme 2 Pathways
Enzyme 2 Reactions
  • 5-methyltetrahydrofolate + NADP+ = 5,10-methylenetetrahydrofolate + NADPH + H+
Enzyme 2 Pfam Domain Function
Enzyme 2 Signals
  • None
Enzyme 2 Transmembrane Regions
  • None
Enzyme 2 Essentiality Not Available
Enzyme 2 GenBank ID Protein 6139053 Link Image
Enzyme 2 UniProtKB/Swiss-Prot ID P42898 Link Image
Enzyme 2 UniProtKB/Swiss-Prot Entry Name MTHR_HUMAN Link Image
Enzyme 2 PDB ID Not Available
Enzyme 2 Cellular Location Not Available
Enzyme 2 Gene Sequence >1971 bp 
ATGGTGAACGAAGCCAGAGGAAACAGCAGCCTCAACCCCTGCTTGGAGGGCAGTGCCAGC
AGTGGCAGTGAGAGCTCCAAAGATAGTTCGAGATGTTCCACCCCGGGCCTGGACCCTGAG
CGGCATGAGAGACTCCGGGAGAAGATGAGGCGGCGATTGGAATCTGGTGACAAGTGGTTC
TCCCTGGAATTCTTCCCTCCTCGAACTGCTGAGGGAGCTGTCAATCTCATCTCAAGGTTT
GACCGGATGGCAGCAGGTGGCCCCCTCTACATAGACGTGACCTGGCACCCAGCAGGTGAC
CCTGGCTCAGACAAGGAGACCTCCTCCATGATGATCGCCAGCACCGCCGTGAACTACTGT
GGCCTGGAGACCATCCTGCACATGACCTGCTGCCGTCAGCGCCTGGAGGAGATCACGGGC
CATCTGCACAAAGCTAAGCAGCTGGGCCTGAAGAACATCATGGCGCTGCGGGGAGACCCA
ATAGGTGACCAGTGGGAAGAGGAGGAGGGAGGCTTCAACTACGCAGTGGACCTGGTGAAG
CACATCCGAAGTGAGTTTGGTGACTACTTTGACATCTGTGTGGCAGGTTACCCCAAAGGC
CACCCCGAAGCAGGGAGCTTTGAGGCTGACCTGAAGCACTTGAAGGAGAAGGTGTCTGCG
GGAGCCGATTTCATCATCACGCAGCTTTTCTTTGAGGCTGACACATTCTTCCGCTTTGTG
AAGGCATGCACCGACATGGGCATCACTTGCCCCATCGTCCCCGGGATCTTTCCCATCCAG
GGCTACCACTCCCTTCGGCAGCTTGTGAAGCTGTCCAAGCTGGAGGTGCCACAGGAGATC
AAGGACGTGATTGAGCCAATCAAAGACAACGATGCTGCCATCCGCAACTATGGCATCGAG
CTGGCCGTGAGCCTGTGCCAGGAGCTTCTGGCCAGTGGCTTGGTGCCAGGCCTCCACTTC
TACACCCTCAACCGCGAGATGGCTACCACAGAGGTGCTGAAGCGCCTGGGGATGTGGACT
GAGGACCCCAGGCGTCCCCTACCCTGGGCTCTCAGTGCCCACCCCAAGCGCCGAGAGGAA
GATGTACGTCCCATCTTCTGGGCCTCCAGACCAAAGAGTTACATCTACCGTACCCAGGAG
TGGGACGAGTTCCCTAACGGCCGCTGGGGCAATTCCTCTTCCCCTGCCTTTGGGGAGCTG
AAGGACTACTACCTCTTCTACCTGAAGAGCAAGTCCCCCAAGGAGGAGCTGCTGAAGATG
TGGGGGGAGGAGCTGACCAGTGAAGCAAGTGTCTTTGAAGTCTTTGTTCTTTACCTCTCG
GGAGAACCAAACCGGAATGGTCACAAAGTGACTTGCCTGCCCTGGAACGATGAGCCCCTG
GCGGCTGAGACCAGCCTGCTGAAGGAGGAGCTGCTGCGGGTGAACCGCCAGGGCATCCTC
ACCATCAACTCACAGCCCAACATCAACGGGAAGCCGTCCTCCGACCCCATCGTGGGCTGG
GGCCCCAGCGGGGGCTATGTCTTCCAGAAGGCCTACTTAGAGTTTTTCACTTCCCGCGAG
ACAGCGGAAGCACTTCTGCAAGTGCTGAAGAAGTACGAGCTCCGGGTTAATTACCACCTT
GTCAATGTGAAGGGTGAAAACATCACCAATGCCCCTGAACTGCAGCCGAATGCTGTCACT
TGGGGCATCTTCCCTGGGCGAGAGATCATCCAGCCCACCGTAGTGGATCCCGTCAGCTTC
ATGTTCTGGAAGGACGAGGCCTTTGCCCTGTGGATTGAGCGGTGGGGAAAGCTGTATGAG
GAGGAGTCCCCGTCCCGCACCATCATCCAGTACATCCACGACAACTACTTCCTGGTCAAC
CTGGTGGACAATGACTTCCCACTGGACAACTGCCTCTGGCAGGTGGTGGAAGACACATTG
GAGCTTCTCAACAGGCCCACCCAGAATGCGAGAGAAACGGAGGCTCCATGA
Enzyme 2 GenBank Gene ID U09806 Link Image
Enzyme 2 GeneCard ID MTHFR Link Image
Enzyme 2 GenAtlas ID MTHFR Link Image
Enzyme 2 HGNC ID HGNC:7436 Link Image
Enzyme 2 Chromosome Location 1
Enzyme 2 Locus 1p36.3
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 General References
  1. Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, Rozen R: Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet. 1994 Jun;7(2):195-200. [PubMed Link Image]
  2. Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, Rozen R: Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification. Nat Genet. 1994 Aug;7(4):551. [PubMed Link Image]
  3. Goyette P, Pai A, Milos R, Frosst P, Tran P, Chen Z, Chan M, Rozen R: Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR) Mamm Genome. 1998 Aug;9(8):652-6. [PubMed Link Image]
  4. Goyette P, Frosst P, Rosenblatt DS, Rozen R: Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. Am J Hum Genet. 1995 May;56(5):1052-9. [PubMed Link Image]
  5. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP, et al.: A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995 May;10(1):111-3. [PubMed Link Image]
  6. Goyette P, Christensen B, Rosenblatt DS, Rozen R: Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR. Am J Hum Genet. 1996 Dec;59(6):1268-75. [PubMed Link Image]
  7. Schneider JA, Rees DC, Liu YT, Clegg JB: Worldwide distribution of a common methylenetetrahydrofolate reductase mutation. Am J Hum Genet. 1998 May;62(5):1258-60. [PubMed Link Image]
  8. van der Put NM, Gabreels F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK, van den Heuvel LP, Blom HJ: A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998 May;62(5):1044-51. [PubMed Link Image]
  9. Kluijtmans LA, Wendel U, Stevens EM, van den Heuvel LP, Trijbels FJ, Blom HJ: Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency. Eur J Hum Genet. 1998 May-Jun;6(3):257-65. [PubMed Link Image]
  10. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R: A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998 Jul;64(3):169-72. [PubMed Link Image]
  11. Sibani S, Christensen B, O'Ferrall E, Saadi I, Hiou-Tim F, Rosenblatt DS, Rozen R: Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria. Hum Mutat. 2000;15(3):280-7. [PubMed Link Image]
Enzyme 2 Metabolite References Not Available