Alterations of fatty acid metabolism and membrane fluidity in peroxisome-defective mutant ZP102 cells |
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Authors: | Nagura Michiaki Saito Makiko Iwamori Masao Sakakihara Yoichi Igarashi Takashi |
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Affiliation: | (1) Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyoku Tokyo, 113-8655 Tokyo, Japan;(2) Department of Biochemistry, Faculty of Science and Technology, Kinki University, 7-3-1 Hongo, Bunkyoku. Tokyo, 113-8655 Osaka, Japan |
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Abstract: | We investigated lipid composition and FA metabolism in Chinese hamster ovary (CHO-K1) cells and Pex5-mutated CHO-K1 (ZP102) cells to clarify the biochemical bases of peroxisome biogenesis disorders (PBD). ZP102 cells have
defective peroxisomes and exhibit impairments of peroxisomal β-oxidation of FA and plasmalogen biosynthesis. In addition,
we identified FA metabolic alterations in the synthesis of several classes of lipids in ZP102 cells. The concentration of
FFA in ZP102 cells was twice that in CHO-K1 cells, but methyl esters and TAG were decreased in ZP102 cells in comparison with
control cells. Also, ceramide monohexoside (CMH) concentration with ZP102 cells was significantly increased compared with
the control cells. The FA molecular species, particularly the saturated to unsaturated ratios, of individual lipids also differed
between the two cell types. The rate of incorporation of 14C]-labeled saturated acids into sphingomyelin (SM) and CMH in ZP102 cells was lugher than that in CHO-K1 cells. Lignoceric
acid incorporated into cells was predominantly utilized for the synthesis of SM at 24 h after removal of 14C] lignoceric acid from the culture medium. ZP102 cells showed higher fluorescence anisotropy of 1,3,5-diphenylhexatriene,
corresponding to lower membrane mobility than in CHO-K1 cells. In particular, alteration of lipid metabolism by a Pex5 mutation enhanced metabolism of saturated FA and sphingolipids. This may be related to the reduced membrane fluidity of ZP102
cells, which has been implicated in the dysfunction of membrane-linked processes in PBD. |
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