Geranylgeraniol oxidase activity involved in oxidative formation of geranylgeranoic acid in human hepatoma cells
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- Mitake Maiko
- Molecular and Cellular Biology, Graduate School of Human Health Science, University of Nagasaki, Nagayo, Nagasaki, 851-2195, Japan
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- Shidoji Yoshihiro
- Molecular and Cellular Biology, Graduate School of Human Health Science, University of Nagasaki, Nagayo, Nagasaki, 851-2195, Japan
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Abstract
Geranylgeranoic acid (GGA), a 20-carbon acyclic polyprenoic acid (all-trans 3,7,11,15-tetramethyl- 2,4,6,10,14-hexadecatetraenoic acid) and its derivatives were developed as synthetic “acyclic retinoids” for cancer chemoprevention. Previously, we have shown the natural occurrence of GGA in various medicinal herbs and reported enzymatic formation of GGA from geranylgeraniol (GGOH) through geranylgeranial (GGal) by rat liver homogenates. Here, we present several lines of evidence that a putative GGOH oxidase is involved in GGA synthesis by human hepatoma cell lysates. First, conversion of GGOH to GGal did not require exogenous NAD+, whereas the conversion from GGal to GGA absolutely required additional NAD+. Second, GGal synthesis from GGOH was coupled with consumption of oxygen from the reaction mixture. Third, GGOH-dependent GGal synthesis activity was proteinase K-resistant and even enhanced by proteinase K treatment; GGOH oxidase activity was enriched in the mitochondrial fraction. Finally, recombinant human monoamine oxidase (MAO)-B, but not MAO-A catalyzed oxidation of GGOH to GGal. These data suggest that a putative mitochondrial GGOH oxidase is involved in the initial step of GGA synthesis from GGOH.
Journal
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- Biomedical Research
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Biomedical Research 33 (1), 15-24, 2012
Biomedical Research Press
