Peroxisomal very long chain fatty acid beta-oxidation activity is determined by the level of adrenodeukodystrophy protein (ALDP) expression.

[neonatal adrenoleukodystrophy]

Impaired peroxisomal beta -oxidation of saturated very long chain fatty acids (VLCFA , >/=C 2 2 :0 ) results in increased VLCFA levels in the tissues and body fluids of patients with disorders of peroxisomal biogenesis (i .e ., Zellweger syndrome and neonatal adrenoleukodystrophy ) and single peroxisomal protein defects (i .e ., X-linked adrenoleukodystrophy (X-ALD ) and acyl-CoA oxidase deficiency ). We show that SV 40 T transformation also results in impaired peroxisomal beta -oxidation and VLCFA accumulation despite the presence of abundant peroxisomes . To explore the mechanism responsible for this observation , we have examined expression of key components of peroxisomal VLCFA beta -oxidation . We found that expression of both acyl-CoA oxidase , the rate limiting enzyme of peroxisomal VLCFA beta -oxidation and the adrenoleukodystrophy protein (ALDP ), the defective gene product in X-ALD , are reduced after SV 40 T transformation . Surprisingly , ALDP overexpression by itself restores peroxisomal VLCFA beta -oxidation in SV 40 T -transformed control and X-ALD cells . These results demonstrate that ALDP is a fundamental component in VLCFA peroxisomal beta -oxidation and may serve as a "gatekeeper " for VLCFA homeostasis .