Glyceryl ether monooxygenase resembles aromatic amino acid hydroxylases in metal ion and tetrahydrobiopterin dependence.
Glyceryl ether monooxygenase is a tetrahydrobiopterin-dependent membrane-bound enzyme which catalyses the cleavage of lipid ethers into glycerol and the corresponding aldehyde. Despite many different characterisation and purification attempts, so far no gene and primary sequence have been assigned to this enzyme. The seven other tetrahydrobiopterin-dependent enzymes can be divided in the family of aromatic amino acid hydroxylases - comprising phenylalanine hydroxylase, tyrosine hydroxylase and the two tryptophan hydroxylases - and into the three nitric oxide synthases. We tested the influences of different metal ions and metal ion chelators on glyceryl ether monooxygenase, phenylalanine hydroxylase and nitric oxide synthase activity to elucidate the relationship of glyceryl ether monooxygenase to these two families. 1,10-Phenanthroline, an inhibitor of non-heme iron-dependent enzymes, was able to potently block glyceryl ether monooxygenase as well as phenylalanine hydroxylase, but had no effect on inducible nitric oxide synthase. Two tetrahydrobiopterin analogues, N(5)-methyltetrahydrobiopterin and 4-aminotetrahydrobiopterin, had a similar impact on glyceryl ether monooxygenase activity, as has already been shown for phenylalanine hydroxylase. These observations point to a close analogy of the role of tetrahydrobiopterin in glyceryl ether monooxygenase and in aromatic amino acid hydroxylases and suggest that glyceryl ether monooxygenase may require a non-heme iron for catalysis.
Watschinger
Katrin
K
Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Fritz-Pregl-Str. 3/VI, A-6020 Innsbruck, Austria.
Keller
Markus A
MA
Hermetter
Albin
A
Golderer
Georg
G
Werner-Felmayer
Gabriele
G
Werner
Ernst R
ER
D024322:Amino Acids, Aromatic / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D004492:Edetic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005995:Glyceryl Ethers / Q000378:metabolism*; D008099:Liver / Q000166:cytology; D008670:Metals / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008861:Microsomes / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010618:Phenanthrolines / Q000494:pharmacology; D010651:Phenylalanine Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D015203:Reproducibility of Results; D012995:Solubility
D024322:Amino Acids, Aromatic; D005995:Glyceryl Ethers; D008670:Metals; D010618:Phenanthrolines; D001708:Biopterins; D004492:Edetic Acid; D006899:Mixed Function Oxygenases; D019001:Nitric Oxide Synthase; D010651:Phenylalanine Hydroxylase; C003402:sapropterin; C025205:1,10-phenanthroline