Polished rice as natural sources of cancer-preventing geranylgeranoic acid

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Author(s)

    • Muraguchi Takashi
    • Molecular and Cellular Biology, Graduate School of Human Health Sciences, Siebold University of Nagasaki
    • Okamoto Kyoko
    • Molecular and Cellular Biology, Graduate School of Human Health Sciences, Siebold University of Nagasaki
    • Mitake Maiko
    • Molecular and Cellular Biology, Graduate School of Human Health Sciences, Siebold University of Nagasaki
    • Ogawa Hiroko
    • Molecular and Cellular Biology, Graduate School of Human Health Sciences, Siebold University of Nagasaki
    • Shidoji Yoshihiro
    • Molecular and Cellular Biology, Graduate School of Human Health Sciences, Siebold University of Nagasaki

Abstract

Geranylgeranoic acid, a 20-carbon polyprenoic acid (all-<i>trans</i> 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecatetraenoic acid) and its derivatives were previously developed as synthetic “acyclic retinoids” for cancer chemoprevention. Recently, we demonstrated the natural occurrence of geranylgeranoic acid in various medicinal herbs (Shidoji and Ogawa, 2004). In this present study, we present several lines of evidence to demonstrate that geranylgeranyl diphosphate taken in foods could be metabolized to GGA through geranylgeraniol and geranylgeranyl aldehyde via the following steps: 1) The conversion from geranylgeranyl diphosphate to geranylgeraniol was demonstrated to occur by the action of bovine intestinal alkaline phosphatase, with a <i>K</i><sub>m</sub> of 46.1 μM. 2) Geranylgeraniol oxidase-mediated conversion of geranylgeraniol to geranylgeranyl aldehyde was revealed in rat liver homogenates, which activity was mainly localized in the mitochondrial fraction. The mitochondrial enzyme showed a <i>K</i><sub>m</sub> of 92.9 μM. 3) The conversion of geranylgeranyl aldehyde to geranylgeranoic acid by geranylgeranyl aldehyde dehydrogenase in rat liver homogenates was absolutely dependent on exogenously added NAD<sup>+</sup> or NADP<sup>+</sup>. The <i>K</i><sub>m</sub> of the mitochondrial geranylgeranyl aldehyde dehydrogenase was 27.5 μM for geranylgeranyl aldehyde. Taken together, our data suggest that cancer preventive geranylgeranoic acid could be a physiological metabolite from commonly consumed foods.<br>

Journal

  • Journal of Clinical Biochemistry and Nutrition

    Journal of Clinical Biochemistry and Nutrition 49(1), 8-15, 2011

    SOCIETY FOR FREE RADICAL RESEARCH JAPAN

Codes

  • NII Article ID (NAID)
    130004879265
  • Text Lang
    ENG
  • ISSN
    0912-0009
  • Data Source
    J-STAGE 
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