Studies on the degradation of [U-3H]-phytanic acid and [U-3H]-pristanic acid in cultured fibroblasts from children with peroxisomal disorders.
Up till now, errors of phytanic acid metabolism in children with peroxisomal disorders have been estimated by measuring 14CO2 formation from 1-14C-labelled phytanic acid in different systems. In the present work we have incubated both 1-14C- and U-3H-labelled phytanic acid and U-3H-labelled pristanic acid with cultured fibroblasts from healthy children as well as from children with peroxisomal disorders. In cultured fibroblasts from healthy children, [U-3H]-pristanic acid was degraded at a rate 60 times that of [U-3H]-phytanic acid, indicating that the initial degradation of phytanic acid into pristanic acid is the rate-limiting step in the overall conversion. In cultured fibroblasts from children with the Zellweger syndrome and infantile Refsum disease, the degradation of both phytanic acid and pristanic acid, was severely impaired (10-40 and 10-30 times, respectively), but the degradation of pristanic acid was still more than 20 times higher than that of phytanic acid in these disorders. In fibroblasts from a child with rhizomelic chondrodysplasia punctata the rate of degradation of U-3H- and 1-14C-labelled phytanic acid was markedly reduced whereas the rate of degradation of U-3H-labelled pristanic acid was normal. No evidence was obtained for elongation of phytanic or pristanic acid in the different fibroblastic cultures. It is concluded that both the degradation of phytanic acid and pristanic acid may be affected in peroxisomal disorders. The possibility that phytanic acidaemia in these disorders is due to product inhibition of accumulated pristanic acid seems to be excluded. The pristanic acidaemia sometimes seen is likely to be due to dietary pristanic acid rather than to de novo synthesized pristanic acid from accumulated phytanic acid.
Kase
B F
BF
Department of Paediatric Research, Rikshospitalet, National Hospital, Oslo, Norway.
Björkhem
I
I
D002478:Cells, Cultured; D002648:Child; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008830:Microbodies / Q000378:metabolism*; D010831:Phytanic Acid / Q000378:metabolism*; D014316:Tritium; D015211:Zellweger Syndrome / Q000378:metabolism
D005227:Fatty Acids; D014316:Tritium; D010831:Phytanic Acid; C002844:pristanic acid