Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2010 Aug 03;10731:13672-7. doi: 10.1073/pnas.1002404107.
Show Gene links
Show Anatomy links
Identification of the gene encoding alkylglycerol monooxygenase defines a third class of tetrahydrobiopterin-dependent enzymes.
Watschinger K, Keller MA, Golderer G, Hermann M, Maglione M, Sarg B, Lindner HH, Hermetter A, Werner-Felmayer G, Konrat R, Hulo N, Werner ER.
???displayArticle.abstract??? Alkylglycerol monooxygenase (glyceryl-ether monooxygenase, EC 1.14.16.5) is the only enzyme known to cleave the O-alkyl bond of ether lipids which are essential components of brain membranes, protect the eye from cataract, interfere or mediate signalling processes, and are required for spermatogenesis. Along with phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase, and nitric oxide synthase, alkylglycerol monooxygenase is one of five known enzymatic reactions which depend on tetrahydrobiopterin. Although first described in 1964, no sequence had been assigned to this enzyme so far since it lost activity upon protein purification attempts. A functional library screen using pools of plasmids of a rat liver expression library transfected to CHO cells was also unsuccessful. We therefore selected human candidate genes by bioinformatic approaches and by proteomic analysis of partially purified enzyme and tested alkylglycerol monooxygenase activity in CHO cells transfected with expression plasmids. Transmembrane protein 195, a predicted membrane protein with unassigned function which occurs in bilateral animals, was found to encode for tetrahydrobiopterin-dependent alkylglycerol monooxygenase. This sequence assignment was confirmed by injection of transmembrane protein 195 cRNA into Xenopus laevis oocytes. Transmembrane protein 195 shows no sequence homology to aromatic amino acid hydroxylases or nitric oxide synthases, but contains the fatty acid hydroxylase motif. This motif is found in enzymes which contain a diiron center and which carry out hydroxylations of lipids at aliphatic carbon atoms like alkylglycerol monooxygenase. This sequence assignment suggests that alkylglycerol monooxygenase forms a distinct third group among tetrahydrobiopterin-dependent enzymes.
P 19764-B05 Austrian Science Fund FWF, P 22406-B18 Austrian Science Fund FWF, P 19764 Austrian Science Fund FWF, P 22406 Austrian Science Fund FWF, FWF_P 19764 Austrian Science Fund FWF, FWF_P 22406 Austrian Science Fund FWF
Alderson,
The human FA2H gene encodes a fatty acid 2-hydroxylase.
2004, Pubmed
Alderson,
The human FA2H gene encodes a fatty acid 2-hydroxylase.
2004,
Pubmed Bogdan,
Nitric oxide and the immune response.
2001,
Pubmed Bredt,
Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase.
1991,
Pubmed Cho,
Inducible nitric oxide synthase: identification of amino acid residues essential for dimerization and binding of tetrahydrobiopterin.
1995,
Pubmed Citron,
Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism.
1993,
Pubmed Elshourbagy,
Molecular cloning and characterization of the major endothelin receptor subtype in porcine cerebellum.
1992,
Pubmed
,
Xenbase Finn,
The Pfam protein families database.
2008,
Pubmed Gorgas,
The ether lipid-deficient mouse: tracking down plasmalogen functions.
2006,
Pubmed Gorren,
Nitric-oxide synthase: a cytochrome P450 family foster child.
2007,
Pubmed Graessler,
Top-down lipidomics reveals ether lipid deficiency in blood plasma of hypertensive patients.
2009,
Pubmed Keller,
Monitoring of fatty aldehyde dehydrogenase by formation of pyrenedecanoic acid from pyrenedecanal.
2010,
Pubmed Konrat,
The protein meta-structure: a novel concept for chemical and molecular biology.
2009,
Pubmed Leahy,
Evolution of the soluble diiron monooxygenases.
2003,
Pubmed Lespinet,
ORENZA: a web resource for studying ORphan ENZyme activities.
2006,
Pubmed Li,
Characterization of yeast methyl sterol oxidase (ERG25) and identification of a human homologue.
1996,
Pubmed Lund,
cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism.
1998,
Pubmed Maeda,
Transcript annotation in FANTOM3: mouse gene catalog based on physical cDNAs.
2006,
Pubmed Mandal,
Interleukin-1-induced ether-linked diglycerides inhibit calcium-insensitive protein kinase C isotypes. Implications for growth senescence.
1997,
Pubmed Marletta,
Catalysis by nitric oxide synthase.
1998,
Pubmed Matsushima,
Molecular cloning and mapping of a human cDNA (SC5DL) encoding a protein homologous to fungal sterol-C5-desaturase.
1996,
Pubmed Mustafa,
Signaling by gasotransmitters.
2009,
Pubmed Palmer,
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor.
,
Pubmed Shanklin,
Desaturases: emerging models for understanding functional diversification of diiron-containing enzymes.
2009,
Pubmed Shanklin,
Eight histidine residues are catalytically essential in a membrane-associated iron enzyme, stearoyl-CoA desaturase, and are conserved in alkane hydroxylase and xylene monooxygenase.
1994,
Pubmed Sobieszek,
Phosphorylation of myorod (catchin) by kinases tightly associated to molluscan and vertebrate smooth muscle myosins.
2006,
Pubmed Stuehr,
Mammalian nitric oxide synthases.
1999,
Pubmed Taguchi,
Glyceryl-ether monooxygenase [EC 1.14.16.5]. A microsomal enzyme of ether lipid metabolism.
1998,
Pubmed Tamura,
MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0.
2007,
Pubmed Thöny,
Tetrahydrobiopterin biosynthesis, regeneration and functions.
2000,
Pubmed TIETZ,
A NEW PTERIDINE-REQUIRING ENZYME SYSTEM FOR THE OXIDATION OF GLYCERYL ETHERS.
1964,
Pubmed Watschinger,
Glyceryl ether monooxygenase resembles aromatic amino acid hydroxylases in metal ion and tetrahydrobiopterin dependence.
2009,
Pubmed Werner,
Widespread occurrence of glyceryl ether monooxygenase activity in rat tissues detected by a novel assay.
2007,
Pubmed Werner-Felmayer,
Tetrahydrobiopterin biosynthesis, utilization and pharmacological effects.
2002,
Pubmed Wild,
Physarum polycephalum expresses a dihydropteridine reductase with selectivity for pterin substrates with a 6-(1', 2'-dihydroxypropyl) substitution.
2003,
Pubmed
