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Tetrahydrobiopterin‐dependent Alkylglycerol Monooxygenase: From Gene Identification to Novel Insights into Etherlipid Degradation
Author(s) -
Watschinger Katrin,
Keller Markus A.,
Golderer Georg,
Hermann Martin,
Hermetter Albin,
WernerFelmayer Gabriele,
Werner Ernst R.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.913.8
Subject(s) - aldehyde dehydrogenase , monooxygenase , biochemistry , tetrahydrobiopterin , chemistry , endoplasmic reticulum , gene , enzyme , microbiology and biotechnology , biology , cofactor , cytochrome p450
Alkylglycerol monooxygenase is the only enzyme able to degrade alkylglycerols by cleaving the ether bond in a tetrahydrobiopterin‐dependent manner yielding a toxic aldehyde which is further oxidized by fatty aldehyde dehydrogenase. Using candidate gene expression we have recently identified the gene coding for alkylglycerol monooxygenase (Watschinger K. et al, Proc Natl Acad Sci U S A, 2010, 107:13672‐7). Here, by silencing of TMEM195 in murine macrophage RAW 264.7 cells using lentiviral constructs we confirm that this gene is responsible for tetrahydrobiopterin‐dependent alkylglycerol cleavage. To investigate the metabolic interplay with fatty aldehyde dehydrogenase we transiently expressed fluorescently‐tagged constructs of alkylglycerol monooxygenase with one of the two splice variants of fatty aldehyde dehydrogenase and analyzed the localization by live cell confocal microscopy. While the major splice variant of fatty aldehyde dehydrogenase (V2) is expressed together with alkylglycerol monooxygenase in the endoplasmic reticulum, the second splice variant (V1) was located exclusively to peroxisomes. This allows the conclusion that the V2 variant is responsible for detoxification of the aldehyde produced by alkylglycerol monooxygenase whereas the V1 variant could be responsible for aldehyde elimination originating from other sources. Supported by the Austrian Science Fund (FWF) P22406.