Role of lipids in the Neurospora crassa membrane: IV. Biochemical and electrophysiological changes caused by growth on phytanic acid.

Neurospora crassa strain cel, which is deficient in fatty acid synthesis, was grown with phytanic acid supplementation. The temperature dependence of membrane potential is increased by growth on phytanic acid. A temperature change of 40 degrees C produces a change of 184 mV in phytanic acid-grown cells as compared to a 50 mV change for cel grown on palmitic acid or wild-type. Membrane resistance (measured as DC input resistance) of phytanic acid-grown cells did not differ from cel grown on palmitic acid or wild-type. Lipid analysis of cel grown on phytanic acid revealed approximately 7 mole percent phytanic acid incorporation into phospholipids, no change in phospholipid base composition, a reduction of ergosterol content from 80 to 30 percent, and the induction of beta sitosterol, a sterol not usually present in Neurospora. beta sitosterol accounted for approximately 60 percent of the sterol present. Incorporation of 7 mole percent phytanic acid into phospholipids lowers the phase transition temperature by approximately 5 degrees C, and decreases the heat content of the phase transition (delta H) slightly. Results are discussed in relation to Refsum's disease, a human neurological disorder associated with high plasma levels of phytanic acid. It is proposed that high intracellular phytanic acid concentration induces novel sterol synthesis and that the incorporation of the novel sterol into the membrane is responsible for the increased temperature sensitivity of membrane potential. The excitable membrane deficits observed in patients with Refsum's disease may be explained by such a mechanism.