Essential Chemical structure of Liver Peroxisome Proliferators

Abstract

Since chemical structures of peroxisome proliferators are so much versatile, it has been difficult to identify the essential chemical form required for the induction of peroxisome proliferation. From the fact that perfluorinated fatty acids (C 10, C 8 and C 4), the un-metabolizable derivatives of fatty acids, induced the peroxisome proliferation markedly in rat liver, the free fatty acids were considered as the true inducer. Perfluoroalkanes (C 12 and C 8) which possess no functional groups did not show any inducing activity, supporting this concept. Although the CoA form of fatty acids have been claimed as the intrinsic form for the peroxisome proliferator, this possibility should be negligible because perfluorooctane sulphonate, another unmetabolizable compound which is never converted into CoA form, induced the peroxisome proliferation. From these results, we have come to the conclution that the un-metabolizable lipophilic anion is the essential chemical structure common in the peroxisome proliferators. All of the known peroxisome proliferators are included into this category, as such or after receiving metabolism.