MTHFR deficiency (Homo sapiens)

From WikiPathways

Revision as of 14:48, 23 May 2019 by Josienlandman (Talk | contribs)
Jump to: navigation, search
7819244293622Cytochrome C releaseInflux of calciumSAM is decreased in MTHFR deficiencyProtein homocysteinylationDeficiency of S-adenosylmethionineInadequate methionine synthesisThis is just a example of a inhibited methylation. Due to SAM deficiency all methylation reactions are inhibited.OligodendrocyteAuto-oxidationMitochrondrial dysfunctionSAM is decreased in MTHFR deficiencyToxic intermediates from the elevated levels of homocysteineMTHFR deficiency106DAGMetRSASMTMyelin componentsSGMS 1[Myelin basic protein]-N-methylarginineEHMT1HNMTHomocysteine thiolactoneHomocysteineCASP3Folate metabolism and related disordersEHMT2Ca2+SAMCholineDNMT3APRMTCDP-cholineCeramideCytochrome cBHMTBetaine aldehydeDimethylglycinereactive oxygen speciesPEMTBADHphosphatidylcholineNMDA 2D5,10-Methylene-THFCASP9MethioninesphingomyelinCOMTNMDA 1MTHFRDNMT3Bbetaine5-Methyl-THFSAHCHDHphosphatidylethanolaminePhosphocholineOxidative DamageCholine kinase alphaApoptosis[Myelin basic protein]-arginineNMDA 2AbetaineCholineCHPT-1CCT-alphaSAMSAMSAMMBP methylation is decreased in MTHFR deficiencyMBP is a component of myelin sheat. Methylation is needed for structure stability.Homocystein levels areelevated in MTHFR deficiency.HomocysteineExcitotoxicity5, 8HomocysteineLipid & Protein oxidationCa2+HomocysteineCytochrome cCa2+DNMT1EC 2.1.1.79EC 2.1.1.72


Description

There are currently three hypothesis for demyelination in the Central Nervous System (CNS) of methylenetetrahydrofolate reductase (MTHFR) deficient patients. These three possible mechanisms are: inadequate methionine synthesis, a deficiency of S-adenosylmethionine or accumulation of toxic intermediates from the elevated levels of homocysteine. This pathway includes all three of these possible mechanisms. This pathway was inspired by Chapter 10 of the book of Blau(ISBN 3642403360 (978-3642403361)) and the paper by Prasad et al. (2011, https://www.ncbi.nlm.nih.gov/pubmed/21778025). For an overview of disorders related to folate metabolism and transport, please see [1].

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Petras M, Tatarkova Z, Kovalska M, Mokra D, Dobrota D, Lehotsky J, Drgova A; ''Hyperhomocysteinemia as a risk factor for the neuronal system disorders.''; J Physiol Pharmacol, 2014 PubMed Europe PMC Scholia
  2. Pajares MA, Perez-Sala D; ''Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism?''; Cell Mol Life Sci, 2006 PubMed Europe PMC Scholia
  3. Poddar R, Paul S; ''Novel crosstalk between ERK MAPK and p38 MAPK leads to homocysteine-NMDA receptor-mediated neuronal cell death.''; J Neurochem, 2013 PubMed Europe PMC Scholia
  4. Prasad AN, Rupar CA, Prasad C; ''Methylenetetrahydrofolate reductase (MTHFR) deficiency and infantile epilepsy.''; Brain Dev, 2011 PubMed Europe PMC Scholia
  5. Sharma GS, Singh LR; ''Conformational status of cytochrome c upon N-homocysteinylation: Implications to cytochrome c release.''; Arch Biochem Biophys, 2017 PubMed Europe PMC Scholia
  6. James SJ, Melnyk S, Pogribna M, Pogribny IP, Caudill MA; ''Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology.''; J Nutr, 2002 PubMed Europe PMC Scholia
  7. Li Z, Vance DE; ''Phosphatidylcholine and choline homeostasis.''; J Lipid Res, 2008 PubMed Europe PMC Scholia
  8. Ueland PM; ''Choline and betaine in health and disease.''; J Inherit Metab Dis, 2011 PubMed Europe PMC Scholia
  9. Gault CR, Obeid LM, Hannun YA; ''An overview of sphingolipid metabolism: from synthesis to breakdown.''; Adv Exp Med Biol, 2010 PubMed Europe PMC Scholia
  10. Fan X, Jin WY, Wang YT; ''The NMDA receptor complex: a multifunctional machine at the glutamatergic synapse.''; Front Cell Neurosci, 2014 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128288view01:59, 30 January 2024EweitzFix typo, standardize case
128287view01:57, 30 January 2024EweitzRefine colors, tailor node dimensions
128286view01:53, 30 January 2024EweitzFix typos, otherwise copyedit, standardize case
128285view01:51, 30 January 2024EweitzImprove color contrast, for readability
124269view12:34, 6 October 2022DeSlUpdated sphingomyelin ID to more general one
124268view12:24, 6 October 2022DeSlUpdated interactions to textLabels to graphical Lines
124267view12:21, 6 October 2022DeSlAdded tranlocations iso arrows
120407view09:21, 30 November 2021Fehrhartboxed pathway nodes
108079view11:48, 28 November 2019FehrhartOntology Term : 'disease pathway' added !
106792view13:27, 17 September 2019MaintBotHMDB identifier normalization
104404view14:54, 23 May 2019JosienlandmanAdded Rhea identifier and modified ChEBI
104402view14:48, 23 May 2019JosienlandmanAdded Rhea identifier for betaine aldehyde -> betaine
104399view14:28, 23 May 2019JosienlandmanAdded Rhea identifiers and modified ChEBIs
104052view20:02, 28 April 2019EgonwAdded some redundant/empty Biopax content.
104022view17:37, 25 April 2019IreneHemelModified description
102720view14:02, 21 January 2019DeSlModified description
98310view11:48, 20 August 2018DeSlModified description
98306view11:37, 20 August 2018DeSlChanged layout of disease, added linkout to related PW.
97981view20:31, 28 June 2018KhanspersModified description
97945view09:03, 26 June 2018Jessev1993lay out changes
97944view09:00, 26 June 2018Jessev1993changed layout
97890view13:41, 19 June 2018DeSlChanged wrong characters in lit ref.
97889view13:38, 19 June 2018DeSlAdded competitive inhibitor info.
97888view11:36, 19 June 2018Jessev1993added enzymes inhibited by SAH
97877view08:27, 13 June 2018Jessev1993changed pathway link myelin components
97864view09:17, 12 June 2018Jessev1993added annotation for MetRS
97863view08:53, 12 June 2018Jessev1993Changed cytochrome c from metabolite to protein
97850view09:35, 11 June 2018DeSlRemoved Ec + space for linkout.
97729view11:35, 7 June 2018Jessev1993Added enzymes inhibited by SAH
97592view08:40, 28 May 2018DeSlOntology Term : 'S-adenosylmethionine homeostasis pathway' added !
97591view08:40, 28 May 2018DeSlChanged lit. ref with weird symbols.
97590view08:35, 28 May 2018DeSlAdded comments for each node related to its hypothesis.
97584view06:22, 27 May 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
97573view12:09, 25 May 2018Jessev1993
97572view12:05, 25 May 2018Jessev1993Checked lines, changed when needed. Put text label also in commment
97569view11:18, 25 May 2018DeSlCleaned up layout for better readability
97568view10:58, 25 May 2018DeSlOntology Term : 'methylenetetrahydrofolate reductase deficiency pathway' added !
97567view10:56, 25 May 2018DeSlModified description
97440view13:40, 17 May 2018Jessev1993added text labels
97420view07:03, 16 May 2018Jessev1993Ontology Term : 'oligodendrocyte' added !
97419view07:01, 16 May 2018Jessev1993Ontology Term : 'inherited metabolic disorder' added !
97418view06:59, 16 May 2018Jessev1993Ontology Term : 'folate metabolic pathway' added !
97417view06:58, 16 May 2018Jessev1993Ontology Term : 'hyperhomocysteinemia disease pathway' added !
97402view12:51, 15 May 2018Jessev1993New pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
5,10-Methylene-THFMetaboliteCHEBI:1989 (ChEBI)
5-Methyl-THFMetaboliteCHEBI:15641 (ChEBI)
ASMTGeneProductENSG00000196433 (Ensembl) SAMdef Hypothesis
ApoptosisPathwayWP254 (WikiPathways)
BADHProteinP49419 (Uniprot-TrEMBL) Methionine Hypothesis
BHMTProteinQ93088 (Uniprot-TrEMBL)
Betaine aldehydeMetaboliteCHEBI:15710 (ChEBI) Methionine Hypothesis
CASP3GeneProductENSG00000164305 (Ensembl) Toxic Hypothesis
CASP9GeneProductENSG00000132906 (Ensembl) Toxic Hypothesis
CCT-alphaProteinP49585 (Uniprot-TrEMBL) Methionine Hypothesis
CDP-cholineMetaboliteCHEBI:58779 (ChEBI) Methionine Hypothesis
CHDHProteinQ8NE62 (Uniprot-TrEMBL) Methionine Hypothesis
CHPT-1ProteinQ8WUD6 (Uniprot-TrEMBL) Methionine Hypothesis
COMTGeneProductENSG00000093010 (Ensembl) SAMdef Hypothesis
Ca2+MetaboliteCHEBI:29108 (ChEBI) Toxic Hypothesis
CeramideMetaboliteCHEBI:17761 (ChEBI) Methionine Hypothesis
Choline kinase alphaProteinP35790 (Uniprot-TrEMBL) Methionine Hypothesis
CholineMetaboliteCHEBI:15354 (ChEBI) Methionine Hypothesis
Cytochrome cProteinG4XXL9 (Uniprot-TrEMBL) Toxic Hypothesis
DAGMetaboliteCHEBI:18035 (ChEBI) Methionine Hypothesis
DNMT1GeneProductENSG00000130816 (Ensembl) SAMdef Hypothesis
DNMT3AGeneProductENSG00000119772 (Ensembl) SAMdef Hypothesis
DNMT3BGeneProductENSG00000088305 (Ensembl) SAMdef Hypothesis
DimethylglycineMetaboliteCHEBI:17724 (ChEBI)
EC 2.1.1.72Protein2.1.1.72 (Enzyme Nomenclature)
EC 2.1.1.79Protein2.1.1.79 (Enzyme Nomenclature)
EHMT1GeneProductENSG00000181090 (Ensembl) SAMdef Hypothesis
EHMT2GeneProductENSG00000204371 (Ensembl)
Folate metabolism and related disordersPathwayWP4259 (WikiPathways)
HNMTProteinP50135 (Uniprot-TrEMBL)
Homocysteine thiolactoneMetaboliteHMDB02287 (HMDB) Toxic Hypothesis
HomocysteineMetaboliteCHEBI:17230 (ChEBI) Toxic Hypothesis
HomocysteineMetaboliteCHEBI:58199 (ChEBI)
MTHFRGeneProductENSG00000177000 (Ensembl)
MetRSProteinP56192 (Uniprot-TrEMBL)
  • Needs annotation
  • Toxic Hypothesis
MethionineMetaboliteCHEBI:57844 (ChEBI)
Myelin componentsPathwayWP4304 (WikiPathways)
NMDA 1ProteinQ05586 (Uniprot-TrEMBL) Toxic Hypothesis
NMDA 2AProteinF5GZ52 (Uniprot-TrEMBL) Toxic Hypothesis
NMDA 2DProteinO15399 (Uniprot-TrEMBL) Toxic Hypothesis
Oxidative DamagePathwayWP3941 (WikiPathways)
PEMTProteinQ9UBM1 (Uniprot-TrEMBL) Methionine Hypothesis
PRMTProteinB4E0W7 (Uniprot-TrEMBL) SAMdef Hypothesis
PhosphocholineMetaboliteCHEBI:295975 (ChEBI) Methionine Hypothesis
SAHMetaboliteCHEBI:16680 (ChEBI) SAMdef Hypothesis
SAMMetaboliteCHEBI:67040 (ChEBI) Methionine Hypothesis
SGMS 1ProteinD3DWC4 (Uniprot-TrEMBL) Methionine Hypothesis
[Myelin basic protein]-N-methylarginineMetaboliteCHEBI:10167 (ChEBI) SAMdef Hypothesis
[Myelin basic protein]-arginineMetaboliteCHEBI:10166 (ChEBI) SAMdef Hypothesis
betaineMetaboliteCHEBI:17750 (ChEBI) Methionine Hypothesis
phosphatidylcholineMetaboliteCHEBI:49183 (ChEBI) Methionine Hypothesis
phosphatidylethanolamineMetaboliteCHEBI:16038 (ChEBI) Methionine Hypothesis
reactive oxygen speciesMetaboliteQ424361 (Wikidata) Toxic Hypothesis
sphingomyelinMetaboliteCHEBI:62490 (ChEBI) Methionine Hypothesis

Annotated Interactions

SourceTargetTypeDatabase referenceComment
Betaine aldehydebetainemim-conversion15306 (Rhea)
CholineBetaine aldehydemim-conversion17434 (Rhea)
CholinePhosphocholinemim-conversion12838 (Rhea)
HomocysteineMethioninemim-conversion22337 (Rhea)
PhosphocholineCDP-cholinemim-conversion18998 (Rhea)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP4288"
Personal tools