Peroxisomal beta-oxidation of polyunsaturated long chain fatty acids in human fibroblasts. The polyunsaturated and the saturated long chain fatty acids are retroconverted by the same acyl-CoA oxidase.
The metabolism of the C22 unsaturated fatty acids erucic acid (22:1(n-9)), adrenic acid (22:4(n-6)), docosapentaenoic acid (22:5(n-3)) and docosahexaenoic acid (22:6(n-3)) was studied in cultured fibroblasts from patients with acyl-CoA oxidase deficiency, the Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD) and normal controls. [3-14C] 22:4 (n-6) and [3-14C] 22:5 (n-3) were shortened (retroconverted) to [1-14C] 20:4 (n-6) and [1-14C] 20:5 (n-3), respectively, in normal and X-ALD fibroblasts. In Zellweger and acyl-CoA oxidase deficient fibroblasts these reactions were deficient. Since the retroconversion is normal in X-ALD fibroblasts peroxisomal very long chain (lignoceryl) CoA ligase is probably not required for the activation of C22 unsaturated fatty acids. The present work with fibroblasts from patients with a specific acyl-CoA oxidase deficiency, previously shown to have a deficient peroxisomal clofibrate-inducible acyl-CoA oxidase, and which accumulate 24:0 and 26:0 fatty acids, supports the view that this enzyme is responsible for the chain-shortening of docosahexaenoic acid (22:6(n-3)), erucic acid (22:1(n-9)), docosapentaenoic acid (22:5(n-3)), and adrenic acid (22:4(n-6)) as well.
Christensen
E
E
Institute of Clinical Biochemistry, Rikshospitalet, University of Oslo, Norway.
Woldseth
B
B
Hagve
T A
TA
Poll-The
B T
BT
Wanders
R J
RJ
Sprecher
H
H
Stokke
O
O
Christophersen
B O
BO
D042962:Acyl-CoA Oxidase; D000326:Adrenoleukodystrophy / Q000201:enzymology; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000378:metabolism; D004883:Erucic Acids / Q000378:metabolism; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008830:Microbodies / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000172:deficiency / Q000378:metabolism*; D015211:Zellweger Syndrome / Q000201:enzymology
D004883:Erucic Acids; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; C049811:erucic acid; C011395:adrenic acid; D004281:Docosahexaenoic Acids; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; C026219:docosapentaenoic acid