Wax biosynthesis (Homo sapiens)

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1, 3341, 2131, 2, 4endoplasmic reticulum lumencytosolperoxisomal matrixPALM-PALMatROLFAR2HXOLARACOHAWAT1CoA-SHNADPHarachidyl esterNADP+PalmCoAatR-PALMPALM-CoAAWAT2H+HXOLCoA-SHFAR1CoA-SHAcyl-CoA1, 4


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. Enzymes that catalyze two reactions of wax biosynthesis have been characterized in humans. FAR1 and FAR2 catalyze the reduction of fatty acids to fatty alcohols in the peroxisome and AWAT1 and AWAT2 catalyze the reaction of fatty alcohols and acyl-CoA in the cytosol to form wax esters. The existence of a transport process, otherwise uncharacterized, to move fatty alcohols from the peroxisome to the cytosol is inferred from the observation that cultured cells that do not normally synthesize waxes can be induced to do so by co-transfection with DNA constructs encoding FAR and AWAT enzymes (Cheng & Russell 2004a,b). View original pathway at:Reactome.


Pathway is converted from Reactome ID: 8848584
Reactome version: 66
Reactome Author 
Reactome Author: D'Eustachio, Peter

Quality Tags

Ontology Terms



  1. Cheng JB, Russell DW.; ''Mammalian wax biosynthesis. II. Expression cloning of wax synthase cDNAs encoding a member of the acyltransferase enzyme family.''; PubMed
  2. 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
  3. Cheng JB, Russell DW.; ''Mammalian wax biosynthesis. I. Identification of two fatty acyl-Coenzyme A reductases with different substrate specificities and tissue distributions.''; PubMed
  4. 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


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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


View all...
NameTypeDatabase referenceComment
ARACOHMetaboliteCHEBI:75627 (ChEBI)
AWAT1ProteinQ58HT5 (Uniprot-TrEMBL)
AWAT2ProteinQ6E213 (Uniprot-TrEMBL)
Acyl-CoAMetaboliteCHEBI:17984 (ChEBI)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
FAR1ProteinQ8WVX9 (Uniprot-TrEMBL)
FAR2ProteinQ96K12 (Uniprot-TrEMBL)
H+MetaboliteCHEBI:15378 (ChEBI)
HXOLMetaboliteCHEBI:16125 (ChEBI)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
PALM-CoAMetaboliteCHEBI:15525 (ChEBI)
PALM-PALMMetaboliteCHEBI:75584 (ChEBI)
PalmCoAMetaboliteCHEBI:15525 (ChEBI)
arachidyl esterMetaboliteCHEBI:10036 (ChEBI)
atR-PALMMetaboliteCHEBI:17616 (ChEBI)
atROLMetaboliteCHEBI:17336 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
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-8848582 (Reactome)
CoA-SHArrowR-HSA-8848585 (Reactome)
FAR1mim-catalysisR-HSA-390425 (Reactome)
FAR2mim-catalysisR-HSA-390438 (Reactome)
H+R-HSA-390425 (Reactome)
H+R-HSA-390438 (Reactome)
HXOLArrowR-HSA-390425 (Reactome)
HXOLArrowR-HSA-390438 (Reactome)
HXOLArrowR-HSA-8848586 (Reactome)
HXOLR-HSA-8848582 (Reactome)
HXOLR-HSA-8848586 (Reactome)
NADP+ArrowR-HSA-390425 (Reactome)
NADP+ArrowR-HSA-390438 (Reactome)
NADPHR-HSA-390425 (Reactome)
NADPHR-HSA-390438 (Reactome)
PALM-CoAR-HSA-8848582 (Reactome)
PALM-CoAR-HSA-8848585 (Reactome)
PALM-PALMArrowR-HSA-8848582 (Reactome)
PalmCoAR-HSA-390425 (Reactome)
PalmCoAR-HSA-390438 (Reactome)
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-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-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 (Cheng & Russell 2004; Turkish et al. 2005).
R-HSA-8848586 (Reactome) The existence of a mechanism to transport HXOL (hexadecanol) from the peroxisomal matrix to the cytosol 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)
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