The Zellweger syndrome: deficient conversion of docosahexaenoic acid (22:6(n-3)) to eicosapentaenoic acid (20:5(n-3)) and normal delta 4-desaturase activity in cultured skin fibroblasts.

Abstract

The metabolism of docosahexaenoic acid (22:6(n-3)) and adrenic acid (22:4(n-6)) was studied in cultured fibroblasts from patients with the Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD) and normal controls. It was shown that [4,5- 3H]22:6(n-3) is retroconverted to labelled eicosapentaenoic acid (20:5(n-3)) in normal and X-ALD fibroblasts, while this conversion is deficient in Zellweger fibroblasts. [U- 14C]Eicosapentaenoic acid (20:5(n-3)) is elongated to docosapentaenoic acid (22:5(n-3)) in all three cell lines. With [U- 14C]20:5(n-3) as the substrate, shorter fatty acids were not detected. With [4,5- 3H]22:6(n-3) as the substrate, labelled fatty acids were esterified in the phospholipid- and triacylglycerol-fraction to approximately the same extent in all three cell lines. [2- 14C]Adrenic acid (22:4(n-6)) was desaturated to 22:5(n-6) and elongated to 24:4(n-6) in all three cell lines and to the largest extent in the Zellweger fibroblasts. This agrees with the view that the delta 4-desaturase is not a peroxisomal enzyme. The observation that the retroconversion of 22:6(n-3) to 20:5(n-3) is deficient in Zellweger fibroblasts strongly suggest that the beta-oxidation step in the retroconversion is a peroxisomal function. Peroxisomal very-long-chain (lignoceroyl) CoA ligase is probably not required for the activation of 22:6(n-3), since the retroconversion to 20:5(n-3) is normal in X-ALD fibroblasts.

• Authors: M Grønn, E Christensen, T A Hagve, B O Christophersen
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1044 Issue 2 Pg. 249-54 (May 22 1990) ISSN: 0006-3002 [Print] Netherlands
• PMID: 2140517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Docosahexaenoic Acids
• Eicosapentaenoic Acid
• Fatty Acid Desaturases
• Linoleoyl-CoA Desaturase

Topics

• Adrenoleukodystrophy (metabolism)
• Cells, Cultured
• Docosahexaenoic Acids (metabolism)
• Eicosapentaenoic Acid (metabolism)
• Fatty Acid Desaturases (metabolism)
• Fibroblasts
• Humans
• Linoleoyl-CoA Desaturase
• Zellweger Syndrome (enzymology, metabolism)