The beta-oxidation of arachidonic acid and the synthesis of docosahexaenoic acid are selectively and consistently altered in skin fibroblasts from three Zellweger patients versus X-adrenoleukodystrophy, Alzheimer and control subjects.
The beta-oxidation of [3H] arachidonic acid (AA; 20:4 n-6) and the conversion of [1-14C]eicosapentaenoic acid (EPA, 20:5 n-3) to docosahexaenoic acid (DHA, 22:6 n-3) have been studied in skin fibroblasts from patients with inherited peroxisomal diseases, such as Zellweger (ZW) and X-linked adrenoleukodystrophy (X-ALD), from patients with Alzheimer's disease (AD), a non-inherited neuropathology, and from controls. EPA is not converted to DHA, while there is enhanced formation of the intermediate product 22:5 n-3 in ZW, when compared to X-ALD, AD and controls. We also confirmed that AA is not beta-oxidized to 4,7,10-hexadecatrienoic acid (16:3), a metabolite produced by peroxisomes, while being more effectively converted to the elongation product 22:4, in ZW, in comparison to X-ALD, AD and controls. The data demonstrate a defect in DHA synthesis and in AA beta-oxidation, and the occurrence of associated adaptative modifications in the metabolism of these long chain PUFA, in three Italian ZW patients.
Petroni
A
A
Institute of Pharmacological Sciences, University of Milan, Italy. petroni@imiucca.csi.unimi.it
Bertagnolio
B
B
La Spada
P
P
Blasevich
M
M
Papini
N
N
Govoni
S
S
Rimoldi
M
M
Galli
C
C
D000326:Adrenoleukodystrophy / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D015211:Zellweger Syndrome / Q000378:metabolism*
D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid