MTHFR deficiency (Homo sapiens)

From WikiPathways

Revision as of 08:35, 28 May 2018 by DeSl (Talk | contribs)
Jump to: navigation, search
174336323886OligodendrocyteDeficiency of S-adenosylmethionineAuto-oxidationInadequate methionine synthesisProtein homocysteinylationThis is just a example of a inhibited methylation. Due to SAM deficiency all methylation reactions are inhibited.Mitochrondrial dysfunctionSAM is decreased in MTHFR deficiencyToxic intermediates from the elevated levels of homocysteineCytochrome C releaseInflux of calciumSAM is decreased in MTHFR deficiency29PhosphocholineCeramidebetaineHomocysteineCDP-cholinePRMTNMDA 15,10-Methylene-THFBetaine aldehyde[Myelin basic protein]-N-methylarginine[Myelin basic protein]-arginineMTHFR deficiencysphingomyelinMethionineMetRSSAH5-Methyl-THFSAMBHMTreactive oxygen speciesBADHCHDHCholine kinase alphaDAGMyelin componentsCASP9CASP3Oxidative DamageCytochrome CNMDA 2AphosphatidylcholineApoptosisMTHFRSGMS 1Homocysteine thiolactoneDimethylglycineCholineCa2+PEMTphosphatidylethanolamineNMDA 2DbetaineCholineCHPT-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.HomocysteineExcitotoxicityHomocysteine5, 7Inhibitor of methyltransferases.Lipid & Protein oxidationCa2+HomocysteineCytochrome CCa2+


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)
BHMTProteinQ93088 (Uniprot-TrEMBL)
Betaine aldehydeMetaboliteCHEBI:15710 (ChEBI)
CASP3GeneProductENSG00000164305 (Ensembl)
CASP9GeneProductENSG00000132906 (Ensembl)
CCT-alphaProteinP49585 (Uniprot-TrEMBL)
CDP-cholineMetaboliteCHEBI:58779 (ChEBI)
CHDHProteinQ8NE62 (Uniprot-TrEMBL)
CHPT-1ProteinQ8WUD6 (Uniprot-TrEMBL)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
CeramideMetaboliteCHEBI:17761 (ChEBI)
Choline kinase alphaProteinP35790 (Uniprot-TrEMBL)
CholineMetaboliteCHEBI:15354 (ChEBI)
Cytochrome CMetaboliteCHEBI:18070 (ChEBI)
DAGMetaboliteCHEBI:18035 (ChEBI)
DimethylglycineMetaboliteCHEBI:17724 (ChEBI)
Homocysteine thiolactoneMetaboliteHMDB02287 (HMDB)
HomocysteineMetaboliteCHEBI:17230 (ChEBI)
MTHFR deficiency
MTHFRGeneProductENSG00000177000 (Ensembl)
MetRSProtein
  • Needs annotation
  • Type your comment here
MethionineMetaboliteCHEBI:16643 (ChEBI)
Myelin componentsPathwayWP4293 (WikiPathways)
NMDA 1ProteinQ05586 (Uniprot-TrEMBL)
NMDA 2AProteinF5GZ52 (Uniprot-TrEMBL)
NMDA 2DProteinO15399 (Uniprot-TrEMBL)
Oxidative DamagePathwayWP3941 (WikiPathways)
PEMTProteinQ9UBM1 (Uniprot-TrEMBL)
PRMTProteinB4E0W7 (Uniprot-TrEMBL)
PhosphocholineMetaboliteCHEBI:18132 (ChEBI)
SAHMetaboliteCHEBI:16680 (ChEBI)
SAMMetaboliteCHEBI:67040 (ChEBI)
SGMS 1ProteinD3DWC4 (Uniprot-TrEMBL)
[Myelin basic protein]-N-methylarginineMetaboliteCHEBI:10167 (ChEBI)
[Myelin basic protein]-arginineMetaboliteCHEBI:10166 (ChEBI)
betaineMetaboliteCHEBI:17750 (ChEBI)
phosphatidylcholineMetaboliteCHEBI:49183 (ChEBI)
phosphatidylethanolamineMetaboliteCHEBI:16038 (ChEBI)
reactive oxygen speciesMetaboliteQ424361 (Wikidata)
sphingomyelinMetaboliteCHEBI:62490 (ChEBI)

Annotated Interactions

No annotated interactions

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