Finding Homes for Orphan Cytochrome P450s: CYP4V2 and CYP4F22 in Disease States

  1. Edward J. Kelly1,
  2. Mariko Nakano2,
  3. Priyanka Rohatgi1,
  4. Vladimir Yarov-Yarovoy3 and
  5. Allan E. Rettie2
  1. 1 Department of Pharmaceutics, University of Washington, Seattle, WA 98195
  2. 3 Department of Pharmacology, University of Washington, Seattle, WA 98195
  3. 2 Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195


Genetic analyses have identified a wide spectrum of mutations in the CYP4V2 gene from patients suffering from Bietti’s crystalline corneoretinal dystrophy, and mutations in the CYP4F22 gene have been linked to lamellar ichthyosis. These strong gene–disease associations will be better understood if we can elucidate the substrate specificity of the heretofore “orphan” P450s and unravel the biochemical pathways that go awry in disease states. The complex biotransformations that underlie eicosanoid signaling, however, pose great challenges for the enzymologist seeking to assign specific metabolic roles to these members of the CYP4 family. Inductive reasoning and modeling are crucial tools for designing the experiments that will define disease progression in terms of CYP function.

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