Adrenoleukodystrophy. The chain shortening of erucic acid (22:1(n-9)) and adrenic acid (22:4(n-6)) is deficient in neonatal adrenoleukodystrophy and normal in X-linked adrenoleukodistrophy skin fibroblasts.
The metabolism of long chain unsaturated fatty acids was studied in cultured fibroblasts from patients with X-linked adrenoleukodystrophy (ALD) and with neonatal ALD. By using [14-14C] erucic acid (22:1(n-9)) as substrate it was shown that the peroxisomal beta-oxidation, measured as chain shortening, was impaired in cells from patients with neonatal ALD. The beta-oxidation of adrenic acid (22:4(n-6)), measured as acid-soluble products, was also reduced in the neonatal ALD cells. The peroxisomal beta-oxidation of [14-14C]erucic acid (22:1(n-9)) and [2-14C]adrenic acid (22:4(n-6)) was normal in cells from X-ALD patients. The beta-oxidation, esterification and chain elongation of [1-14C]arachidonic acid (20:4(n-6)) and [1-14C]eicosapentaenoic acid (20:5(n-3)) was normal in both X-linked ALD and in neonatal ALD. Previous studies suggest that the activation of very long chain fatty acids by a lignoceryl (24:0)-CoA ligase is deficient in X-linked ALD, while the peroxisomal beta-oxidation enzymes are deficient in neonatal ALD. The present results suggest that the peroxisomal very long-chain acyl-CoA ligase is not required for activation of unsaturated C20 and C22 fatty acids and that these fatty acids can be efficiently activated by the long chain acyl-(palmityl)-CoA ligase.
Christensen
E
E
Institute of Clinical Biochemistry, University of Oslo, Norway.
Grønn
M
M
Hagve
T A
TA
Kase
B F
BF
Christophersen
B O
BO
D000326:Adrenoleukodystrophy / Q000235:genetics / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002478:Cells, Cultured; D002806:Chondrodysplasia Punctata / Q000378:metabolism; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D004883:Erucic Acids / Q000378:metabolism*; D004951:Esterification; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008830:Microbodies / Q000378:metabolism; D010084:Oxidation-Reduction; D014960:X Chromosome
D001095:Arachidonic Acids; D004883:Erucic Acids; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; C049811:erucic acid; C011395:adrenic acid; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid