KEGG   ENZYME: 1.5.1.53
Entry
EC 1.5.1.53                 Enzyme                                 

Name
methylenetetrahydrofolate reductase (NADPH);
MTHFR (gene name);
methylenetetrahydrofolate (reduced nicotinamide adenine dinucleotide phosphate) reductase;
5,10-methylenetetrahydrofolate reductase (NADPH);
5,10-methylenetetrahydrofolic acid reductase (ambiguous);
5,10-CH2-H4folate reductase (ambiguous);
methylenetetrahydrofolate reductase (NADPH2);
5,10-methylenetetrahydrofolate reductase (ambiguous);
methylenetetrahydrofolate reductase (ambiguous);
N5,10-methylenetetrahydrofolate reductase (ambiguous);
5,10-methylenetetrahydropteroylglutamate reductase (ambiguous);
N5,N10-methylenetetrahydrofolate reductase (ambiguous);
methylenetetrahydrofolic acid reductase (ambiguous);
5-methyltetrahydrofolate:(acceptor) oxidoreductase (incorrect);
5,10-methylenetetrahydrofolate reductase (FADH2) (ambiguous)
Class
Oxidoreductases;
Acting on the CH-NH group of donors;
With NAD+ or NADP+ as acceptor
Sysname
5-methyltetrahydrofolate:NADP+ oxidoreductase
Reaction(IUBMB)
5-methyltetrahydrofolate + NADP+ = 5,10-methylenetetrahydrofolate + NADPH + H+ [RN:R01224]
Reaction(KEGG)
R01224
Substrate
5-methyltetrahydrofolate [CPD:C00440];
NADP+ [CPD:C00006]
Product
5,10-methylenetetrahydrofolate [CPD:C00143];
NADPH [CPD:C00005];
H+ [CPD:C00080]
Comment
A flavoprotein (FAD). The enzyme from yeast and mammals catalyses a physiologically irreversible reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate using NADPH as the electron donor. It plays an important role in folate metabolism by regulating the distribution of one-carbon moieties between cellular methylation reactions and nucleic acid synthesis. The enzyme contains an N-terminal catalytic domain and a C-terminal allosteric regulatory domain that binds S-adenosyl-L-methionine, which acts as an inhibitor. cf. EC 1.5.1.54, methylenetetrahydrofolate reductase (NADH); EC 1.5.1.20, methylenetetrahydrofolate reductase [NAD(P)H]; and EC 1.5.7.1, methylenetetrahydrofolate reductase (ferredoxin).
History
EC 1.5.1.53 created 2021
Pathway
ec00670  One carbon pool by folate
ec01100  Metabolic pathways
ec01120  Microbial metabolism in diverse environments
Orthology
K25004  methylenetetrahydrofolate reductase (NADPH)
Genes
HSA: 4524(MTHFR)
PTR: 469800(MTHFR)
PPS: 100975693(MTHFR)
GGO: 101134157(MTHFR)
PON: 100454623(MTHFR)
NLE: 105738058(MTHFR)
MCC: 714840(MTHFR)
MCF: 102117536(MTHFR)
CSAB: 103225598(MTHFR)
RRO: 104657549(MTHFR)
RBB: 108539360(MTHFR)
CJC: 100391000(MTHFR)
SBQ: 101043467(MTHFR)
MMU: 17769(Mthfr)
MCAL: 110293543(Mthfr)
MPAH: 110323320(Mthfr)
RNO: 362657(Mthfr)
MUN: 110555748(Mthfr)
CGE: 100774930(Mthfr)
NGI: 103747470(Mthfr)
HGL: 101719335(Mthfr)
CCAN: 109697792(Mthfr)
OCU: 100352874(MTHFR)
TUP: 102476978(MTHFR)
CFA: 478230(MTHFR)
VVP: 112929750(MTHFR)
AML: 100469351(MTHFR)
UMR: 103666650(MTHFR)
UAH: 113270501(MTHFR)
ORO: 101367692(MTHFR)
ELK: 111154700
FCA: 101100576(MTHFR)
PTG: 102969340(MTHFR)
PPAD: 109274118(MTHFR)
AJU: 106971872(MTHFR)
BTA: 497032(MTHFR)
BOM: 102286710(MTHFR)
BIU: 109570335(MTHFR)
BBUB: 102395627(MTHFR)
CHX: 102182523(MTHFR)
OAS: 101111645(MTHFR)
SSC: 397180(MTHFR)
CFR: 102505417(MTHFR)
CDK: 105107034(MTHFR)
BACU: 102998853(MTHFR)
LVE: 103079236(MTHFR)
OOR: 101287316(MTHFR)
DLE: 111187289(MTHFR)
PCAD: 102986652(MTHFR)
ECB: 100050979(MTHFR)
EPZ: 103552183(MTHFR)
EAI: 106836668(MTHFR)
MYB: 102245334(MTHFR)
MYD: 102764267(MTHFR)
MNA: 107531557(MTHFR)
HAI: 109381260(MTHFR)
DRO: 112299114(MTHFR)
PALE: 102882062(MTHFR)
RAY: 107513124(MTHFR)
MJV: 108385719(MTHFR)
LAV: 100661160(MTHFR)
TMU: 101359718
MDO: 100018128(MTHFR)
SHR: 100929400(MTHFR)
PCW: 110199057(MTHFR)
OAA: 100086119(MTHFR)
GGA: 419489(MTHFR)
MGP: 100543073(MTHFR)
CJO: 107323372(MTHFR)
NMEL: 110408579(MTHFR)
APLA: 101805333(MTHFR)
ACYG: 106040241(MTHFR)
TGU: 100220660(MTHFR)
LSR: 110479731(MTHFR)
SCAN: 103820847(MTHFR)
GFR: 102033068(MTHFR)
FAB: 101817361(MTHFR)
PHI: 102109675(MTHFR)
PMAJ: 107213633(MTHFR)
CCAE: 111938714(MTHFR)
CCW: 104693242(MTHFR)
ETL: 114056920(MTHFR)
FPG: 101920680(MTHFR)
FCH: 102053108(MTHFR)
CLV: 102089900(MTHFR)
EGZ: 104133086(MTHFR)
NNI: 104009002(MTHFR)
ACUN: 113487781(MTHFR)
PADL: 103918045(MTHFR)
AAM: 106482439(MTHFR)
ASN: 102373612(MTHFR)
AMJ: 102573230(MTHFR)
PSS: 102448267(MTHFR)
CMY: 102945698(MTHFR)
CPIC: 101950023(MTHFR)
ACS: 100554267(mthfr)
PVT: 110073216(MTHFR)
PBI: 103051539(MTHFR)
PMUR: 107294169(MTHFR)
TSR: 106553080
GJA: 107117727(MTHFR)
XLA: 108697556(mthfr.S) 379784(mthfr.L)
XTR: 100125082(mthfr)
NPR: 108799423(MTHFR)
DRE: 567547(mthfr)
SRX: 107710792(mthfr) 107748978
CCAR: 109092734
IPU: 108265037(mthfr)
PHYP: 113533585(mthfr)
AMEX: 103033176(mthfr)
EEE: 113578182(mthfr)
TRU: 101078210(mthfr)
LCO: 104936586(mthfr)
NCC: 104955699
MZE: 101481615(mthfr)
ONL: 100706052(mthfr)
OLA: 101173920(mthfr)
XMA: 102216417(mthfr)
XCO: 114141964(mthfr)
PRET: 103466998(mthfr)
CVG: 107102655(mthfr)
NFU: 107391521(mthfr)
KMR: 108249409(mthfr)
ALIM: 106529348(mthfr)
AOCE: 111566112(mthfr)
CSEM: 103384826(mthfr)
POV: 109630958
LCF: 108900502(mthfr)
SDU: 111233770(mthfr)
SLAL: 111658836(mthfr)
HCQ: 109528734(mthfr)
BPEC: 110165619(mthfr)
MALB: 109951049(mthfr)
SASA: 106572128(mthfr)
ELS: 105013771(mthfr)
SFM: 108924892(mthfr)
PKI: 111859074(mthfr)
LCM: 102358326(MTHFR)
CMK: 103181396(mthfr)
RTP: 109914604(mthfr)
BFO: 118430292
CIN: 100180174
APLC: 110979147
SKO: 100368141(MTHFR)
DME: Dmel_CG7560(CG7560)
DER: 6544580
DSE: 6605265
DSI: Dsimw501_GD14304(Dsim_GD14304)
DAN: 6507885
DSR: 110181246
DPE: 6598998
DMN: 108152200
DWI: 6638944
DAZ: 108614675
DNV: 108652425
DVI: 6623335
MDE: 101899703
LCQ: 111684318
AAG: 5569213
AME: 100578936
BIM: 100748829
BTER: 100645686
CCAL: 108622149
OBB: 114872033
SOC: 105204539
MPHA: 105829361
AEC: 105154491
ACEP: 105621269
PBAR: 105430772
VEM: 105563068
HST: 105185895
DQU: 106745791
CFO: 105256449
LHU: 105668934
PGC: 109861296
OBO: 105277295
PCF: 106789672
NVI: 100117482
CSOL: 105360655
MDL: 103571235
DPA: 109534565
BMOR: 101735471
BMAN: 114249102
PMAC: 106711396
PRAP: 110991352
HAW: 110376495
TNL: 113495626
PXY: 105388246
BTAB: 109032747
ZNE: 110838326
FCD: 110842614
PVM: 113812240
TUT: 107360415
CSCU: 111641837
CEL: CELE_C06A8.1(mthf-1)
BMY: Bm1_35485
TSP: Tsp_08753
CRG: 105340188
MYI: 110460561
OBI: 106882151
ADF: 107327049
HMG: 100207609
AQU: 100636961
SCE: YGL125W(MET13) YPL023C(MET12)
KMX: KLMA_20276(MET13) KLMA_60378(MET12)
NCS: NCAS_0C02530(NCAS0C02530) NCAS_0D03140(NCAS0D03140)
NDI: NDAI_0E03230(NDAI0E03230) NDAI_0I01770(NDAI0I01770)
TPF: TPHA_0C01840(TPHA0C01840) TPHA_0J01830(TPHA0J01830)
TBL: TBLA_0D02780(TBLA0D02780) TBLA_0F02520(TBLA0F02520)
TDL: TDEL_0B01620(TDEL0B01620) TDEL_0G03480(TDEL0G03480)
KAF: KAFR_0A04630(KAFR0A04630) KAFR_0H01590(KAFR0H01590)
CAL: CAALFM_C210460CA(CaO19.5321) CAALFM_C302950CA(MET13)
SLB: AWJ20_3315(MET13) AWJ20_715(MET12)
NTE: NEUTE1DRAFT128536(NEUTE1DRAFT_128536) NEUTE1DRAFT57029(NEUTE1DRAFT_57029)
ANG: ANI_1_1512084(An09g05860) ANI_1_2398024(An02g03270)
PNO: SNOG_10985(SNOG_10984) SNOG_12690
SPO: SPAC343.10(met11) SPAC56F8.10(met9)
ABP: AGABI1DRAFT111963(AGABI1DRAFT_111963) AGABI1DRAFT68194(AGABI1DRAFT_68194)
ABV: AGABI2DRAFT193205(AGABI2DRAFT_193205) AGABI2DRAFT216007(AGABI2DRAFT_216007)
 » show all
Reference
1  [PMID:13817476]
  Authors
DONALDSON KO, KERESZTESY JC.
  Title
Naturally occurring forms of folic acid. I. "Prefolic A": preparation of concentrate and enzymatic conversion to citrovorum factor.
  Journal
J Biol Chem 234:3235-40 (1959)
Reference
2  [PMID:4399897]
  Authors
Kutzbach C, Stokstad EL.
  Title
Mammalian methylenetetrahydrofolate reductase. Partial purification, properties, and inhibition by S-adenosylmethionine.
  Journal
Biochim Biophys Acta 250:459-77 (1971)
DOI:10.1016/0005-2744(71)90247-6
Reference
3  [PMID:6975779]
  Authors
Daubner SC, Matthews RG.
  Title
Purification and properties of methylenetetrahydrofolate reductase from pig liver.
  Journal
J Biol Chem 257:140-5 (1982)
Reference
4  [PMID:2383427]
  Authors
Zhou J, Kang SS, Wong PW, Fournier B, Rozen R.
  Title
Purification and characterization of methylenetetrahydrofolate reductase from human cadaver liver.
  Journal
Biochem Med Metab Biol 43:234-42 (1990)
DOI:10.1016/0885-4505(90)90029-z
Reference
5  [PMID:11729203]
  Authors
Roje S, Chan SY, Kaplan F, Raymond RK, Horne DW, Appling DR, Hanson AD.
  Title
Metabolic engineering in yeast demonstrates that S-adenosylmethionine controls flux through the methylenetetrahydrofolate reductase reaction in vivo.
  Journal
J Biol Chem 277:4056-61 (2002)
DOI:10.1074/jbc.M110651200
Reference
6  [PMID:29891918]
  Authors
Froese DS, Kopec J, Rembeza E, Bezerra GA, Oberholzer AE, Suormala T, Lutz S, Chalk R, Borkowska O, Baumgartner MR, Yue WW.
  Title
Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition.
  Journal
Nat Commun 9:2261 (2018)
DOI:10.1038/s41467-018-04735-2
  Sequence
[hsa:4524] [sce:YPL023C]
Other DBs
ExplorEnz - The Enzyme Database: 1.5.1.53
IUBMB Enzyme Nomenclature: 1.5.1.53
ExPASy - ENZYME nomenclature database: 1.5.1.53
BRENDA, the Enzyme Database: 1.5.1.53
CAS: 71822-25-8

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