The metabolism of 1-11C-labelled derivatives of palmitic (C16:0), arachidonic (C20:4,n-6) lignoceric (
C21:0) and tetracosatetraenoic (C24:4,n-6)
acids was studied in normal skin fibroblast cultures and in cultures of fibroblasts from peroxisome-deficient (
Zellweger's syndrome) patients. Radiolabelled products of the
fatty acids included
carbon dioxide. C14-24 saturated and mono-
unsaturated fatty acids formed from released
acetate either by synthesis de novo or by elongation of endogenous
fatty acids,
fatty acids formed by 2-6-carbon elongation of added substrates, and a number of water-soluble compounds, some of which were tentatively identified as the
amino acids glutamine,
glutamic acid and
asparagine. The labelled
amino acids were found predominantly in the culture medium.
Zellweger's syndrome fibroblasts showed a marked decrease in radiolabelled
carbon dioxide and water-soluble-product formation from (I-14C)-labelled arachidonic, tetracosatetraenoic and lignoceric
acids but not from [I-14C]
palmitic acid, and the production of radiolabelled C14-18
fatty acids was also diminished. However, the elongation of individual
fatty acids was either normal or above normal. Our data support the view that the oxidation of 20:4, 24:4 and 24:0
fatty acids in cultured skin fibroblasts takes place largely in peroxisomes, and further that the
acetyl-CoA released by the beta-oxidation process is available for the synthesis of
fatty acids and
amino acids. We speculate that the generation of C2 units used for synthesis is a major peroxisomal function and that this function is absent or greatly impaired in
Zellweger's syndrome cells.