Geranylgeraniol oxidase activity involved in oxidative formation of geranylgeranoic acid in human hepatoma cells

Riferimento: 
Biomed Res. 2012 Feb;33(1):15-24.
Autori: 
Mitake M, Shidoji Y.
Fonte: 
Biomed Res. 2012 Feb;33(1):15-24.
Anno: 
2012
Azione: 
L'acido geranylgeranoic (GGA) è stato sviluppato come retinoide sintetico "aciclico" per la chemioprevenzione del cancro nelle cellule di epatoma umano.
Target: 
GGA/epatoma umano.

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 geranyl geraniol (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.

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