Tetrahydrobiopterin and alkylglycerol monooxygenase substantially alter the murine macrophage lipidome
Watschinger K., Keller MA., McNeill E., Alam MT., Lai S., Sailer S., Rauch V., Patel J., Hermetter A., Golderer G., Geley S., Werner-Felmayer G., Plumb RS., Astarita G., Ralser M., Channon KM., Werner ER.
Significance We have recently identified the sequence of the ether lipid-cleaving enzyme alkylglycerol monooxygenase. Like nitric oxide synthases and aromatic amino acid hydroxylases, alkylglycerol monooxygenase needs tetrahydrobiopterin as cofactor. Whereas the former enzymes have well-established roles in the cell, the physiology of alkylglycerol monooxygenase is still not clear. Here we show its regulation in murine macrophage differentiation and its dependence on the cofactor tetrahydrobiopterin in live murine macrophage-like RAW264.7 cells. Upon modulation of the activity of alkylglycerol monooxygenase and the key enzyme in tetrahydrobiopterin biosynthesis, we observe extensive changes in various lipid classes ranging from ether lipids to far more complex lipids. These findings point to an important role of tetrahydrobiopterin in cellular lipid homeostasis.