MTHFR deficiency (Homo sapiens)

From WikiPathways

Revision as of 09:17, 12 June 2018 by Jessev1993 (Talk | contribs)
Jump to: navigation, search
576633393924Deficiency of S-adenosylmethionineThis is just a example of a inhibited methylation. Due to SAM deficiency all methylation reactions are inhibited.Influx of calciumMitochrondrial dysfunctionInadequate methionine synthesisSAM is decreased in MTHFR deficiencyToxic intermediates from the elevated levels of homocysteineSAM is decreased in MTHFR deficiencyAuto-oxidationOligodendrocyteProtein homocysteinylationCytochrome C release41SGMS 1CASP3DimethylglycineMethionineHomocysteine thiolactoneNMDA 2DCholine kinase alphaMTHFR deficiencyNMDA 1CeramideMyelin componentsphosphatidylcholineCytochrome cbetaineHomocysteine5-Methyl-THFBADHDAGCHDHPhosphocholineCholineApoptosisCASP9CDP-cholineMetRSCa2+NMDA 2Aphosphatidylethanolamine5,10-Methylene-THFPEMT[Myelin basic protein]-argininereactive oxygen speciesSAHOxidative DamageBetaine aldehydesphingomyelinSAM[Myelin basic protein]-N-methylarginineBHMTPRMTMTHFRbetaineCholineCHPT-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.HomocysteineExcitotoxicityHomocysteine7, 8Lipid & Protein oxidationCa2+HomocysteineCytochrome cCa2+DNMT1EC 2.1.1.79EC 2.1.1.72


Description

In Prasad et al.(2011) three hypothesis of demyelination in CNS of MTHFR deficient patients were given. 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.

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)
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
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)
DimethylglycineMetaboliteCHEBI:17724 (ChEBI)
EC 2.1.1.72Protein2.1.1.72 (Enzyme Nomenclature)
EC 2.1.1.79Protein2.1.1.79 (Enzyme Nomenclature)
Homocysteine thiolactoneMetaboliteHMDB02287 (HMDB) Toxic Hypothesis
HomocysteineMetaboliteCHEBI:17230 (ChEBI) Toxic Hypothesis
MTHFR deficiency
MTHFRGeneProductENSG00000177000 (Ensembl)
MetRSProteinP56192 (Uniprot-TrEMBL)
  • Needs annotation
  • Toxic Hypothesis
MethionineMetaboliteCHEBI:16643 (ChEBI)
Myelin componentsPathwayWP4293 (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:18132 (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

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP4288"
Personal tools