Abstract
Alkylglycerol monooxygenase (E.C. 1.14.16.5), also called glyceryl ether monooxygenase, is a tetrahydrobiopterin-dependent enzyme. It is the only enzyme known to cleave the ether bond of alkylglycerols and lyso-alkylglycerol phospholipids, including lyso-platelet activating factor. Although it has been first described already in 1964, it was not possible so far to purify the protein. It took until 2010 to assign a sequence to this labile integral membrane enzyme by bioinformatic selection of candidate genes, recombinant expression of these, and sensitive monitoring of the enzymatic activity by a fluorescence-based assay. The sequence shows no significant similarity with the other known tetrahydrobiopterin-dependent enzymes but contains the fatty acid hydroxylase protein motif signature. Proteins containing this signature are all labile and catalyze reactions similar to the alkylglycerol monooxygenase reaction. They are thought to use a di-iron centre for catalysis. Site directed mutagenesis of alkylglycerol monooxygenase defined a region of the active site and a conserved glutamate residue important for tetrahydrobiopterin interaction. Current research now focuses on defining a physiological role of this enzyme which occurs not only in mammals but also in commonly used model organisms such as zebrafish and the nematode Caenorhabditis elegans. © 2013 IUBMB Life 65(4):366–372, 2013.
Highlights
In the 1960s, following the characterization of the structure of the tetrahydrobiopterin cofactor of phenylalanine hydroxylase [1], two further tetrahydrobiopterin-dependent aromatic amino acid hydroxylases were soon detected [2,3]
We summarize the current knowledge on the biochemistry of alkylglycerol monooxygenase, assays to measure its activity, its properties, and its occurrence
Tetrahydrobiopterin leaves the reaction as the quinoid 6,7-[8H] dihydrobiopterin. This quinoid dihydrobiopterin is recycled back to tetrahydrobiopterin by dihydropteridine reductase [4,5,9]. This has not been addressed experimentally so far it seems reasonable to assume that the spontaneous dehydratation of 4a-hydroxytetrahydrobiopterin, the initial product of the tetrahydrobiopterin-dependent hydroxylation, to the quinoid 6,7-[8H] dihydrobiopterin is assisted by carbinolamine dehydratase like in the phenylalanine hydroxylase reaction [10,11]
Summary
In the 1960s, following the characterization of the structure of the tetrahydrobiopterin cofactor of phenylalanine hydroxylase [1], two further tetrahydrobiopterin-dependent aromatic amino acid hydroxylases were soon detected [2,3]. It took until the 1980s to describe the three isoforms of the tetrahydrobiopterin-dependent nitric oxide synthases [4]. Alkylglycerol monooxygenase is the only enzyme known to cleave the ether bond in alkylglycerol ether lipids. We summarize the current knowledge on the biochemistry of alkylglycerol monooxygenase, assays to measure its activity, its properties, and its occurrence
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
