title: Effects of phytanic acid on the vitamin E status, lipid composition and physical properties of retinal cell membranes: implications for adult Refsum disease.
abstract: Adult Refsum disease is an inherited disorder in which phytanic acid accumulates in tissues and serum. Two hypotheses have been proposed to explain the pathogenesis of this condition. The molecular distortion hypothesis suggests that phytanic acid may alter membrane composition and structure, thereby affecting membrane function(s). The anti-metabolite hypothesis suggests that an accumulation of phytanic acid in membranes may interfere with vitamin E function. These two hypotheses were investigated by studying the effects of modulating phytanic acid and alpha-tocopherol concentrations on the fatty acid composition and certain physical parameters of cultured retinal cells. Results showed that (a) the phospholipid fraction of retinal cells readily incorporated phytanic acid, (b) the incorporation of phytanic acid increased membrane fluidity, (c) there was no competition for uptake between phytanic acid and alpha-tocopherol, and (d) the incorporation of phytanic acid did not increase the susceptibility of membranes to lipid peroxidation in vitro. These results obtained with cultured retinal cells suggest that the molecular distortion hypothesis, but not the anti-metabolite hypothesis, could explain the pathogenesis of adult Refsum disease. In vitro tissue culture models can, however, only approximate to the much more complex situation that occurs in vivo.
authors.affiliation: Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Young
authors.forename: A W
authors.initials: AW
authors.lastname: Johnson
authors.forename: D P
authors.initials: DP
authors.lastname: Muller
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism*; D008954:Models, Biological; D010743:Phospholipids / Q000378:metabolism; D010831:Phytanic Acid / Q000494:pharmacology*; D051381:Rats; D012035:Refsum Disease / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019572:Retinal Neoplasms / Q000378:metabolism; D012175:Retinoblastoma / Q000378:metabolism; D014407:Tumor Cells, Cultured; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D008563:Membrane Lipids; D010743:Phospholipids; D010831:Phytanic Acid; D024502:alpha-Tocopherol