Biosynthesis and turnover of 1-deoxy-sphingoid bases (Homo sapiens)

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1-4for more information on specific CoA conversions enzyme for this conversion is still unknown CYP4A/F family desaturases can't be degraded like the normal sphingosine pathway 1-deoxy-3-ketosphinganineCYP4A1-deoxysphingadiene1-deoxyceramide1-deoxysphinganine-2OH1-deoxysphinganine-OH1-deoxysphingosine1-deoxysphingosine-OHCyp4f13sphingolipid metabolism pathwayCoA (26:1)CYP4F4Palmitoyl-CoACoA (22:0)CoA (24:0)KDSRL-alanineCoA (16:0)SGPP1ASAH1CoA (18:0)1-deoxysphinganineATPSPTLC2H2OSPHK2SPTLC1CoA (24:1)SPHK11-deoxy-dihydroceramideADPSGPP2CoA (20:0)CoA (26:0)


Description

Biosynthesis and turnover of 1-deoxy-sphingoid bases (1-doexySLs). 1-Deoxysphingolipids differ structurally from canonical SLs as they lack the essential C1-OH group. Consequently, 1-deoxysphingolipids cannot be converted to complex sphingolipids and are not degraded over the canonical catabolic pathways. Further conversion of 1-deoxysphingosine is done by members of the CYP4A/F family. It is however not clear which specific genes are involved in these processes.

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Bibliography

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  1. Michaels S, Wang MZ; ''The revised human liver cytochrome P450 "Pie": absolute protein quantification of CYP4F and CYP3A enzymes using targeted quantitative proteomics.''; Drug Metab Dispos, 2014 PubMed Europe PMC Scholia
  2. Duan J, Merrill AH Jr; ''1-Deoxysphingolipids Encountered Exogenously and Made de Novo: Dangerous Mysteries inside an Enigma.''; J Biol Chem, 2015 PubMed Europe PMC Scholia
  3. Karsai G, Steiner R, Kaech A, Lone MA, von Eckardstein A, Hornemann T; ''Metabolism of HSAN1- and T2DM-associated 1-deoxy-sphingolipids inhibits the migration of fibroblasts.''; J Lipid Res, 2021 PubMed Europe PMC Scholia
  4. Carreira AC, Santos TC, Lone MA, Zupanaciac E, Lloyd-Evans E, de Almeida RFM, Hornemann T, Silva LC; ''Mammalian sphingoid bases: Biophysical, physiological and pathological properties.''; Prog Lipid Res, 2019 PubMed Europe PMC Scholia
  5. Schwartz NU, Mileva I, Gurevich M, Snider J, Hannun YA, Obeid LM; ''Quantifying 1-deoxydihydroceramides and 1-deoxyceramides in mouse nervous system tissue.''; Prostaglandins Other Lipid Mediat, 2019 PubMed Europe PMC Scholia
  6. Simpson AE; ''The cytochrome P450 4 (CYP4) family.''; Gen Pharmacol, 1997 PubMed Europe PMC Scholia
  7. Lone MA, Santos T, Alecu I, Silva LC, Hornemann T; ''1-Deoxysphingolipids.''; Biochim Biophys Acta Mol Cell Biol Lipids, 2019 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
134709view12:19, 26 July 2024EweitzCopyedit, standardize case
121899view08:24, 8 March 2022RoelvO5Ontology Term : 'DOID:0070160' removed !
121884view23:41, 7 March 2022DeSlOntology Term : 'classic metabolic pathway' added !
121883view23:38, 7 March 2022DeSlAdded EC ID for CYP4A
121882view23:36, 7 March 2022DeSlFound EC ID for CYP4F
121881view23:30, 7 March 2022DeSlAnnotate last missing metaolites, added bidirectional conversion as well additional conversion interaction.
121878view23:19, 7 March 2022DeSlAdded ID for 1-deoxysphinganine-2OH
121877view23:17, 7 March 2022DeSlAdded ID for 1-deoxysphinganine-OH
121876view23:09, 7 March 2022DeSlCondensed the pathway
121875view23:07, 7 March 2022DeSlsmall layout changes
121854view20:19, 7 March 2022RoelvO5added reference
121848view15:42, 7 March 2022RoelvO5Ontology Term : 'diabetes mellitus' added !
121847view15:40, 7 March 2022RoelvO5Ontology Term : 'hereditary sensory and autonomic neuropathy type 1' added !
121846view15:35, 7 March 2022RoelvO5Ontology Term : 'atypical hereditary sensory neuropathy' added !
121845view15:33, 7 March 2022RoelvO5update reference
121844view15:31, 7 March 2022RoelvO5update reference
121843view15:29, 7 March 2022RoelvO5update reference
121842view15:28, 7 March 2022RoelvO5update reference
121841view15:25, 7 March 2022RoelvO5update reference
121840view15:22, 7 March 2022RoelvO5removed cyp4f13 node
121838view14:59, 7 March 2022RoelvO5added cyp4f13 identifier
121837view14:54, 7 March 2022RoelvO5added IDs, updated references and lay-out changes
121836view12:08, 7 March 2022RoelvO5Modified title
121668view08:48, 24 February 2022RoelvO5Modified description
121667view08:45, 24 February 2022RoelvO5Modified title
121666view08:43, 24 February 2022RoelvO5Ontology Term : 'sphingolipid metabolic pathway' added !
121665view08:43, 24 February 2022RoelvO5Ontology Term : 'sphingolipid biosynthetic pathway' added !
121664view08:42, 24 February 2022RoelvO5Ontology Term : 'sphingolipidosis pathway' added !
121551view10:49, 21 February 2022RoelvO5
121485view09:44, 18 February 2022RoelvO5coloured the ones without identifier
121396view10:00, 17 February 2022RoelvO5added comments
121368view13:18, 16 February 2022RoelvO5first draft is done
121350view09:43, 16 February 2022RoelvO5
121341view13:10, 15 February 2022RoelvO5
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121324view08:56, 15 February 2022RoelvO5
121204view14:55, 11 February 2022RoelvO5
121203view14:24, 11 February 2022RoelvO5
121194view08:50, 11 February 2022RoelvO5update
121156view08:59, 10 February 2022RoelvO5New pathway

External references

DataNodes

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NameTypeDatabase referenceComment
1-deoxy-3-ketosphinganineMetabolite67176 (ChEBI)
1-deoxy-dihydroceramideMetaboliteCHEBI:67111 (ChEBI)
1-deoxyceramide MetaboliteLMSP0206 (LIPID MAPS)
1-deoxysphingadieneMetabolite
1-deoxysphinganine-2OHMetabolite
1-deoxysphinganine-OHMetabolite
1-deoxysphinganineMetaboliteCHEBI:67106 (ChEBI)
1-deoxysphingosine-OHMetabolite
1-deoxysphingosineMetabolite193222-34-3 (CAS)
ADPMetaboliteCHEBI:456216 (ChEBI)
ASAH1GeneProductENSG00000104763 (Ensembl)
ATPMetaboliteCHEBI:30616 (ChEBI)
CYP4AGeneProduct
CYP4FGeneProduct
CoA (16:0)MetaboliteLMFA07050360 (LIPID MAPS)
CoA (18:0)MetaboliteLMFA07050369 (LIPID MAPS)
CoA (20:0)Metabolite15527 (ChEBI)
CoA (22:0)MetaboliteLMFA07050289 (LIPID MAPS)
CoA (24:0) MetaboliteLMFA07050372 (LIPID MAPS)
CoA (24:1)MetaboliteLMFA07050098 (LIPID MAPS)
CoA (26:0)MetaboliteLMFA07050327 (LIPID MAPS)
CoA (26:1)Metabolite
Cyp4f13GeneProductHowever, CYP4F enzymes are likely more relevant, as over-

expression of the mouse orthologue Cyp4f13 but not of Cyp4a10 in- creased the formation of 1-deoxySL downstream products [26]. Gen- erally, mice express a broader spectrum of Cyp4a and Cyp4f isoenzymes than humans [45] and therefore also seem to have a higher capacity to metabolize 1-deoxySLs. This might explain why 1-deoxySL plasma le- vels are lower in mice compared to humans, which should be con- sidered when studying the physiological and pathophysiological effects

of 1-deoxySL in rodent models.
H2OMetaboliteCHEBI:15377 (ChEBI)
KDSRGeneProductENSG00000119537 (Ensembl)
L-alanineMetaboliteCHEBI:16977 (ChEBI)
Palmitoyl-CoAMetaboliteCHEBI:15525 (ChEBI)
SGPP1GeneProductENSG00000126821 (Ensembl)
SGPP2GeneProductENSG00000163082 (Ensembl)
SPHK1GeneProductENSG00000176170 (Ensembl)
SPHK2GeneProductENSG00000063176 (Ensembl)
SPTLC1GeneProductENSG00000090054 (Ensembl)
SPTLC2GeneProductENSG00000100596 (Ensembl)
desaturases Protein
sphingolipid metabolism pathwayPathwayWP4344 (WikiPathways)

Annotated Interactions

No annotated interactions

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