Wax and plasmalogen biosynthesis (Homo sapiens)

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Bibliography

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

External references

DataNodes

Name	Type	Database reference	Comment
1-Palmitoyl dihydroxyacetone phosphate	Metabolite	CHEBI:17868 (ChEBI)
AGPS	Protein	O00116 (Uniprot-TrEMBL)
ARACOH	Metabolite	CHEBI:75627 (ChEBI)
AWAT1	Protein	Q58HT5 (Uniprot-TrEMBL)
AWAT2	Protein	Q6E213 (Uniprot-TrEMBL)
Acyl-CoA	Metabolite	CHEBI:17984 (ChEBI)
CoA-SH	Metabolite	CHEBI:15346 (ChEBI)
DHAP	Metabolite	CHEBI:57642 (ChEBI)
DHRS7B	Protein	Q6IAN0 (Uniprot-TrEMBL)
FAD	Metabolite	CHEBI:16238 (ChEBI)
FAR1	Protein	Q8WVX9 (Uniprot-TrEMBL)
FAR2	Protein	Q96K12 (Uniprot-TrEMBL)
GNPAT	Protein	O15228 (Uniprot-TrEMBL)
GNPAT:AGPS complex	Complex	R-HSA-76165 (Reactome)
GO3P	Metabolite	CHEBI:17197 (ChEBI)
H+	Metabolite	CHEBI:15378 (ChEBI)
HXDG3P	Metabolite	CHEBI:63818 (ChEBI)
HXOL	Metabolite	CHEBI:16125 (ChEBI)
NADP+	Metabolite	CHEBI:18009 (ChEBI)
NADPH	Metabolite	CHEBI:16474 (ChEBI)
PALM-CoA	Metabolite	CHEBI:15525 (ChEBI)
PALM-PALM	Metabolite	CHEBI:75584 (ChEBI)
PALM	Metabolite	CHEBI:15756 (ChEBI)
PalmCoA	Metabolite	CHEBI:15525 (ChEBI)
arachidyl ester	Metabolite	CHEBI:10036 (ChEBI)
atR-PALM	Metabolite	CHEBI:17616 (ChEBI)
atROL	Metabolite	CHEBI:17336 (ChEBI)

Annotated Interactions

Source	Target	Type	Database reference	Comment
	1-Palmitoyl dihydroxyacetone phosphate	Arrow	R-HSA-75879 (Reactome)
1-Palmitoyl dihydroxyacetone phosphate			R-HSA-390427 (Reactome)
ARACOH			R-HSA-5696424 (Reactome)
AWAT1		mim-catalysis	R-HSA-5696424 (Reactome)
AWAT2		mim-catalysis	R-HSA-8848582 (Reactome)
AWAT2		mim-catalysis	R-HSA-8848585 (Reactome)
Acyl-CoA			R-HSA-5696424 (Reactome)
	CoA-SH	Arrow	R-HSA-390425 (Reactome)
	CoA-SH	Arrow	R-HSA-390438 (Reactome)
	CoA-SH	Arrow	R-HSA-5696424 (Reactome)
	CoA-SH	Arrow	R-HSA-75879 (Reactome)
	CoA-SH	Arrow	R-HSA-8848582 (Reactome)
	CoA-SH	Arrow	R-HSA-8848585 (Reactome)
DHAP			R-HSA-75879 (Reactome)
DHRS7B		mim-catalysis	R-HSA-75883 (Reactome)
FAR1		mim-catalysis	R-HSA-390425 (Reactome)
FAR2		mim-catalysis	R-HSA-390438 (Reactome)
GNPAT:AGPS complex		mim-catalysis	R-HSA-390427 (Reactome)
GNPAT:AGPS complex		mim-catalysis	R-HSA-75879 (Reactome)
	GO3P	Arrow	R-HSA-390402 (Reactome)
	GO3P	Arrow	R-HSA-390427 (Reactome)
GO3P			R-HSA-390402 (Reactome)
GO3P			R-HSA-75883 (Reactome)
H+			R-HSA-390425 (Reactome)
H+			R-HSA-390438 (Reactome)
H+			R-HSA-75883 (Reactome)
	HXDG3P	Arrow	R-HSA-75883 (Reactome)
	HXOL	Arrow	R-HSA-390425 (Reactome)
	HXOL	Arrow	R-HSA-390438 (Reactome)
	HXOL	Arrow	R-HSA-8848586 (Reactome)
HXOL			R-HSA-390427 (Reactome)
HXOL			R-HSA-8848582 (Reactome)
HXOL			R-HSA-8848586 (Reactome)
	NADP+	Arrow	R-HSA-390425 (Reactome)
	NADP+	Arrow	R-HSA-390438 (Reactome)
	NADP+	Arrow	R-HSA-75883 (Reactome)
NADPH			R-HSA-390425 (Reactome)
NADPH			R-HSA-390438 (Reactome)
NADPH			R-HSA-75883 (Reactome)
PALM-CoA			R-HSA-390425 (Reactome)
PALM-CoA			R-HSA-390438 (Reactome)
PALM-CoA			R-HSA-8848582 (Reactome)
PALM-CoA			R-HSA-8848585 (Reactome)
	PALM-PALM	Arrow	R-HSA-8848582 (Reactome)
	PALM	Arrow	R-HSA-390427 (Reactome)
PalmCoA			R-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 ester	Arrow	R-HSA-5696424 (Reactome)
	atR-PALM	Arrow	R-HSA-8848585 (Reactome)
atROL			R-HSA-8848585 (Reactome)