Metabolism of [17,18-3H2]hexacosanoic acid and [15,16-3H2]lignoceric acid in cultured skin fibroblasts from patients with adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN).

We have studied the metabolism of [17,18-3H2]hexacosanoic acid and [15,16-3H2]lignoceric acid in cultured skin fibroblasts from patients with adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN). The successful solubilization of the very long chain fatty acids as albumin conjugates was confirmed by analysis using glycerol density gradient centrifugation. The composition of radioactive fatty acids in total lipids of fibroblasts after culture for 7 days in the presence of [17,18-3H2] hexacosanoic acid or [15,16-3H2]lignoceric acid was analyzed by radio-gas chromatography. Most of the fatty acids added to the culture media were degraded to shorter-chain fatty acids both by control, and ALD or AMN fibroblasts. However, the content of the remaining radioactive hexacosanoic acid or lignoceric acid was much higher in ALD or AMN fibroblasts, and the content of radioactive shorter-chain fatty acids was much lower in ALD or AMN fibroblasts. These results indicate that the degradation of very long chain fatty acids is decreased in ALD, but also that there is a substantial amount of residual activity of their degradation in ALD fibroblasts.