Wax and plasmalogen biosynthesis (Homo sapiens)

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7-9, 115, 6, 12, 153, 421, 2, 91171196, 10, 141, 13peroxisomal matrixendoplasmic reticulum lumencytosolAcyl-CoA1-PalmitoyldihydroxyacetonephosphateFAD AWAT1NADP+NADPHGNPAT PALM-CoADHAPPALM-CoAatROLAGPS NADP+arachidyl esterFAR2HXOLGNPAT:AGPS complexFAR1GO3PAWAT2CoA-SHDHRS7BNADPHPALMARACOHHXDG3PCoA-SHH+atR-PALMCoA-SHH+GO3PHXOLPalmCoAPALM-PALMCoA-SH2, 9


Description

Waxes are esters of long chain fatty acids and long chain fatty alcohols that play an important role in protecting the skin surface from drying and abrasion (Cheng & Russell 2004a,b). Plasmalogens are an abundant subclass of phospholipids. While their functions are not well understood, defects in their metabolism are associated with serious human disease (de Vet et al. 1999; Nagan and Zoeller 2001). The biosynthesis of these two classes of molecules both start with the reduction of palmitoyl-CoA (PALM-CoA) to hexadecan-1-ol (HXOL) so it is convenient to group them here. View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 8848584
Reactome-version 
Reactome version: 73
Reactome Author 
Reactome Author: D'Eustachio, Peter

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Bibliography

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  1. Lodhi IJ, Yin L, Jensen-Urstad AP, Funai K, Coleman T, Baird JH, El Ramahi MK, Razani B, Song H, Fu-Hsu F, Turk J, Semenkovich CF.; ''Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARγ activation to decrease diet-induced obesity.''; PubMed Europe PMC Scholia
  2. Biermann J, van den Bosch H.; ''In vitro processing of the human alkyl-dihydroxyacetonephosphate synthase precursor.''; PubMed Europe PMC Scholia
  3. Datta SC, Ghosh MK, Hajra AK.; ''Purification and properties of acyl/alkyl dihydroxyacetone-phosphate reductase from guinea pig liver peroxisomes.''; PubMed Europe PMC Scholia
  4. Ofman R, Lajmir S, Wanders RJ.; ''Etherphospholipid biosynthesis and dihydroxyactetone-phosphate acyltransferase: resolution of the genomic organization of the human gnpat gene and its use in the identification of novel mutations.''; PubMed Europe PMC Scholia
  5. Yen CL, Brown CH, Monetti M, Farese RV.; ''A human skin multifunctional O-acyltransferase that catalyzes the synthesis of acylglycerols, waxes, and retinyl esters.''; PubMed Europe PMC Scholia
  6. Nagan N, Zoeller RA.; ''Plasmalogens: biosynthesis and functions.''; PubMed Europe PMC Scholia
  7. Ofman R, Hettema EH, Hogenhout EM, Caruso U, Muijsers AO, Wanders RJ.; ''Acyl-CoA:dihydroxyacetonephosphate acyltransferase: cloning of the human cDNA and resolution of the molecular basis in rhizomelic chondrodysplasia punctata type 2.''; PubMed Europe PMC Scholia
  8. Turkish AR, Henneberry AL, Cromley D, Padamsee M, Oelkers P, Bazzi H, Christiano AM, Billheimer JT, Sturley SL.; ''Identification of two novel human acyl-CoA wax alcohol acyltransferases: members of the diacylglycerol acyltransferase 2 (DGAT2) gene superfamily.''; PubMed Europe PMC Scholia
  9. Ofman R, Wanders RJ.; ''Purification of peroxisomal acyl-CoA: dihydroxyacetonephosphate acyltransferase from human placenta.''; PubMed Europe PMC Scholia
  10. Cheng JB, Russell DW.; ''Mammalian wax biosynthesis. II. Expression cloning of wax synthase cDNAs encoding a member of the acyltransferase enzyme family.''; PubMed Europe PMC Scholia
  11. Biermann J, Just WW, Wanders RJ, Van Den Bosch H.; ''Alkyl-dihydroxyacetone phosphate synthase and dihydroxyacetone phosphate acyltransferase form a protein complex in peroxisomes.''; PubMed Europe PMC Scholia
  12. Arne JM, Widjaja-Adhi MA, Hughes T, Huynh KW, Silvaroli JA, Chelstowska S, Moiseenkova-Bell VY, Golczak M.; ''Allosteric modulation of the substrate specificity of acyl-CoA wax alcohol acyltransferase 2.''; PubMed Europe PMC Scholia
  13. de Vet EC, Ijlst L, Oostheim W, Dekker C, Moser HW, van Den Bosch H, Wanders RJ.; ''Ether lipid biosynthesis: alkyl-dihydroxyacetonephosphate synthase protein deficiency leads to reduced dihydroxyacetonephosphate acyltransferase activities.''; PubMed Europe PMC Scholia
  14. Cheng JB, Russell DW.; ''Mammalian wax biosynthesis. I. Identification of two fatty acyl-Coenzyme A reductases with different substrate specificities and tissue distributions.''; PubMed Europe PMC Scholia
  15. de Vet EC, Hilkes YH, Fraaije MW, van den Bosch H.; ''Alkyl-dihydroxyacetonephosphate synthase. Presence and role of flavin adenine dinucleotide.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114737view16:22, 25 January 2021ReactomeTeamReactome version 75
113181view11:24, 2 November 2020ReactomeTeamReactome version 74
112408view15:34, 9 October 2020ReactomeTeamReactome version 73
101312view11:20, 1 November 2018ReactomeTeamreactome version 66
100849view20:51, 31 October 2018ReactomeTeamreactome version 65
100390view19:26, 31 October 2018ReactomeTeamreactome version 64
99937view16:09, 31 October 2018ReactomeTeamreactome version 63
99493view14:43, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99143view12:40, 31 October 2018ReactomeTeamreactome version 62
93755view13:34, 16 August 2017ReactomeTeamreactome version 61
93275view11:19, 9 August 2017ReactomeTeamreactome version 61
87860view11:56, 25 July 2016MirellaKalafatiOntology Term : 'classic metabolic pathway' added !
86354view09:16, 11 July 2016ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
1-Palmitoyl

dihydroxyacetone

phosphate		MetaboliteCHEBI:17868 (ChEBI)
AGPS ProteinO00116 (Uniprot-TrEMBL)
ARACOHMetaboliteCHEBI:75627 (ChEBI)
AWAT1ProteinQ58HT5 (Uniprot-TrEMBL)
AWAT2ProteinQ6E213 (Uniprot-TrEMBL)
Acyl-CoAMetaboliteCHEBI:17984 (ChEBI)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
DHAPMetaboliteCHEBI:57642 (ChEBI)
DHRS7BProteinQ6IAN0 (Uniprot-TrEMBL)
FAD MetaboliteCHEBI:16238 (ChEBI)
FAR1ProteinQ8WVX9 (Uniprot-TrEMBL)
FAR2ProteinQ96K12 (Uniprot-TrEMBL)
GNPAT ProteinO15228 (Uniprot-TrEMBL)
GNPAT:AGPS complexComplexR-HSA-76165 (Reactome)
GO3PMetaboliteCHEBI:17197 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
HXDG3PMetaboliteCHEBI:63818 (ChEBI)
HXOLMetaboliteCHEBI:16125 (ChEBI)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
PALM-CoAMetaboliteCHEBI:15525 (ChEBI)
PALM-PALMMetaboliteCHEBI:75584 (ChEBI)
PALMMetaboliteCHEBI:15756 (ChEBI)
PalmCoAMetaboliteCHEBI:15525 (ChEBI)
arachidyl esterMetaboliteCHEBI:10036 (ChEBI)
atR-PALMMetaboliteCHEBI:17616 (ChEBI)
atROLMetaboliteCHEBI:17336 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
1-Palmitoyl

dihydroxyacetone

phosphate		ArrowR-HSA-75879 (Reactome)
1-Palmitoyl

dihydroxyacetone

phosphate		R-HSA-390427 (Reactome)
ARACOHR-HSA-5696424 (Reactome)
AWAT1mim-catalysisR-HSA-5696424 (Reactome)
AWAT2mim-catalysisR-HSA-8848582 (Reactome)
AWAT2mim-catalysisR-HSA-8848585 (Reactome)
Acyl-CoAR-HSA-5696424 (Reactome)
CoA-SHArrowR-HSA-390425 (Reactome)
CoA-SHArrowR-HSA-390438 (Reactome)
CoA-SHArrowR-HSA-5696424 (Reactome)
CoA-SHArrowR-HSA-75879 (Reactome)
CoA-SHArrowR-HSA-8848582 (Reactome)
CoA-SHArrowR-HSA-8848585 (Reactome)
DHAPR-HSA-75879 (Reactome)
DHRS7Bmim-catalysisR-HSA-75883 (Reactome)
FAR1mim-catalysisR-HSA-390425 (Reactome)
FAR2mim-catalysisR-HSA-390438 (Reactome)
GNPAT:AGPS complexmim-catalysisR-HSA-390427 (Reactome)
GNPAT:AGPS complexmim-catalysisR-HSA-75879 (Reactome)
GO3PArrowR-HSA-390402 (Reactome)
GO3PArrowR-HSA-390427 (Reactome)
GO3PR-HSA-390402 (Reactome)
GO3PR-HSA-75883 (Reactome)
H+R-HSA-390425 (Reactome)
H+R-HSA-390438 (Reactome)
H+R-HSA-75883 (Reactome)
HXDG3PArrowR-HSA-75883 (Reactome)
HXOLArrowR-HSA-390425 (Reactome)
HXOLArrowR-HSA-390438 (Reactome)
HXOLArrowR-HSA-8848586 (Reactome)
HXOLR-HSA-390427 (Reactome)
HXOLR-HSA-8848582 (Reactome)
HXOLR-HSA-8848586 (Reactome)
NADP+ArrowR-HSA-390425 (Reactome)
NADP+ArrowR-HSA-390438 (Reactome)
NADP+ArrowR-HSA-75883 (Reactome)
NADPHR-HSA-390425 (Reactome)
NADPHR-HSA-390438 (Reactome)
NADPHR-HSA-75883 (Reactome)
PALM-CoAR-HSA-390425 (Reactome)
PALM-CoAR-HSA-390438 (Reactome)
PALM-CoAR-HSA-8848582 (Reactome)
PALM-CoAR-HSA-8848585 (Reactome)
PALM-PALMArrowR-HSA-8848582 (Reactome)
PALMArrowR-HSA-390427 (Reactome)
PalmCoAR-HSA-75879 (Reactome)
R-HSA-390402 (Reactome) O-hexadecylglycerone phosphate is synthesized in the peroxisomal matrix but its further metabolism takes place in the cytosol and endoplasmic reticulum. The mechanism by which it leaves the peroxisome is unknown (Nagan and Zoeller 2001).
R-HSA-390425 (Reactome) Peroxisomal fatty acyl-CoA reductase 1 (FAR1) catalyzes the reaction of palmitoyl-CoA (PalmCoA) and 2 NADPH + 2 H+ to form hexadecanol (HXOL), CoASH, and 2 NADP+. As judged from mRNA levels, FAR1 is widely expressed in the body (Cheng and Russell 2004).
R-HSA-390427 (Reactome) Peroxisomal alkylglycerone phosphate synthase (AGPS) catalyzes the reaction of 1-palmitoylglycerone phosphate and hexadecanol to form O-hexadecylglycerone phosphate and palmitate. The active form of the enzyme is post-translationally cleaved to remove its 58 aminoterminal residues, has a molecule of FAD as a cofactor, and occurs in the peroxisome as a complex with glyceronephosphate O-acyltransferase (GNPAT) (Biermann et al. 1999; Bierman and van den Bosch 1999; de Vet et al. 2000).
R-HSA-390438 (Reactome) Peroxisomal fatty acyl-CoA reductase 2 (FAR2) catalyzes the reaction of palmitoyl-CoA (PalmCoA) and 2 NADPH + 2 H+ to form hexadecanol (HXOL), CoASH, and 2 NADP+. As judged from mRNA levels, FAR2 is not widely expressed in the body but is abundant in brain (Cheng and Russell 2004).
R-HSA-5696424 (Reactome) Arachidyl alcohol (ARACOH) is straight-chain fatty alcohol of C20 length used as an emollient in cosmetics. Esterification of alcohols with fatty acids represents the formation of both storage and cytoprotective molecules in the body. Overproduction of these esters is associated with several disease pathologies, including atherosclerosis and obesity. The ER membrane-associated acyl-CoA wax alcohol acyltransferase 1 (AWAT1) mediates the esterification of its preferred substrate ARACOH (Turkish et al. 2005).
R-HSA-75879 (Reactome) Peroxisomal glyceronephosphate O-acyltransferase (GNPAT) catalyzes the reaction of palmitoyl-CoA and DHAP to form 1-palmitoyl glycerone phosphate (1-palmitoyl dihydroxyacetone phosphate) and CoASH. The active form of the enzyme is one subunit of a heterotrimer with two molecules of the alkylglycerone phosphate synthase (AGPS) enzyme (Biermann et al. 1999). It was first purified and characterized biochemically by Ofman and Wanders (1994). Mutations in the GNPAT gene are associated with rhizomelic chondrodysplasia type 2 (Ofman et al. 1998, 2001).
R-HSA-75883 (Reactome) DHRS7B (Dehydrogenase/reductase SDR family member 7B) catalyzes the reaction of NADPH and GO3P (O-hexadecyldihydroxyacetone phosphate) to form HXDG3P (1-hexadecyl glycerol-3-phosphate) and NADP+. The enzyme is associated with the outer face of the peroxisomal membrane; its substrates and products are thought to be cytosolic. The properties of the human enzyme are inferred from those of an activity purified from guinea pig liver (Datta et al. 1990). More recent studies of HXDG3P metabolism in cultured human cells in which DHRS7B activity was knocked down confirm the specificity of the human enzyme (Lodhi et al. 2012).
R-HSA-8848582 (Reactome) AWAT2 (Acyl-CoA wax alcohol acyltransferase 2, also known as MFAT and DC4) associated with the endoplasmic reticulum membrane catalyzes the reaction of HXOL (hexadecanol) and PALM-CoA (palmitoyl-CoA) to form the wax monoester palmityl palmitate. The enzyme also acts efficiently on other long-chain fatty alcohols and fatty acyl CoAs. It is abundant in skin and is thought to play a central role in the synthesis of wax molecules that protect the skin from drying (Cheng & Russell 2004; Turkish et al. 2005; Yen et al. 2005).
R-HSA-8848585 (Reactome) AWAT2 (Acyl-CoA wax alcohol acyltransferase 2, also known as MFAT and DC4) associated with the endoplasmic reticulum membrane catalyzes the reaction of atROL (all-trans retinol) and PALM-CoA (palmitoyl-CoA) to form the ester retinyl palmitate. This ester is thought to provide an inactive storage form of retinol and might play a role in protecting skin, where AWAT2 is most abundant from the effects of UV light (Arne et al. 2017; Yen et al. 2005).
R-HSA-8848586 (Reactome) The existence of a mechanism to transport HXOL (hexadecanol) between the cytosol and the peroxisomal matrix is inferred from studies of wax synthesis in cultured cells (Cheng & Russell 2004). A transporter for HXOL has not been identified.
arachidyl esterArrowR-HSA-5696424 (Reactome)
atR-PALMArrowR-HSA-8848585 (Reactome)
atROLR-HSA-8848585 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP3790"
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