Phytanic acid is a retinoid X receptor ligand

Eur J Biochem. 1996 Feb 15;236(1):328-33. doi: 10.1111/j.1432-1033.1996.00328.x.


Metabolic defects in phytanic acid catabolism have been shown to be connected with a number of human diseases which can lead to lethal defects of the nervous system and other organs. These effects are probably a result of the very high accumulation of phytanic acid in tissues throughout the body, due to defects in phytanic acid oxidation, the peroxisome being a major site for this process. The nuclear hormone receptors peroxisome proliferator-activated receptor and retinoid X receptor (RXR) have been shown to function as transcription factors in the control of the peroxisomal enzyme expression. Known activators of peroxisome proliferator-activated receptor include polyunsaturated fatty acids and, for RXR, the 9-cis isomer of retinoic acid. Here we report that phytanic acid is also a natural ligand for RXR alpha, being able to activate a RXR-responsive promoter. We present evidence that phytanic acid binds to RXR alpha, promotes formation of an RXR alpha/RXR response element complex (as detected by gel retardation), and induces a RXR alpha conformational change similar to that induced by 9-cis-retinoic acid (as detected by protease sensitivity). These results suggest an involvement of RXR alpha in the control of fatty acid metabolism and could imply that RXRs have a role in the disease effects resulting from defective phytanic acid catabolism.

MeSH terms

  • Base Sequence
  • Dose-Response Relationship, Drug
  • Escherichia coli / genetics
  • Humans
  • Ligands
  • Molecular Sequence Data
  • Phytanic Acid / metabolism*
  • Receptors, Retinoic Acid / agonists*
  • Receptors, Retinoic Acid / genetics
  • Recombinant Proteins / metabolism
  • Refsum Disease / metabolism
  • Retinoid X Receptors
  • Transcription Factors / agonists*
  • Transcription Factors / genetics
  • Transcriptional Activation / drug effects
  • Tretinoin / metabolism


  • Ligands
  • Receptors, Retinoic Acid
  • Recombinant Proteins
  • Retinoid X Receptors
  • Transcription Factors
  • Phytanic Acid
  • Tretinoin