Kase B F, Björkhem I
Department of Paediatric Research, Rikshospitalet, National Hospital, Oslo, Norway.
Scand J Clin Lab Invest. 1996 May;56(3):211-7. doi: 10.3109/00365519609088610.
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.
到目前为止，过氧化物酶体疾病患儿植烷酸代谢的误差是通过在不同系统中测量1-14C标记的植烷酸生成14CO2来估计的。在本研究中，我们将1-14C标记和U-3H标记的植烷酸以及U-3H标记的降植烷酸与健康儿童以及过氧化物酶体疾病患儿的培养成纤维细胞一起孵育。在健康儿童的培养成纤维细胞中，[U-3H] - 降植烷酸的降解速率是[U-3H] - 植烷酸的60倍，这表明植烷酸最初降解为降植烷酸是整个转化过程中的限速步骤。在患有 Zellweger 综合征和婴儿型 Refsum 病的患儿的培养成纤维细胞中，植烷酸和降植烷酸的降解均严重受损（分别为正常的10 - 40倍和10 - 30倍），但在这些疾病中，降植烷酸的降解仍比植烷酸高20倍以上。在患有点状软骨发育不良的患儿的成纤维细胞中，U-3H和1-14C标记的植烷酸的降解速率明显降低，而U-3H标记的降植烷酸的降解速率正常。在不同的成纤维细胞培养物中未获得植烷酸或降植烷酸延长的证据。结论是，过氧化物酶体疾病可能会影响植烷酸和降植烷酸的降解。这些疾病中植烷酸血症是由于积累的降植烷酸的产物抑制所致的可能性似乎被排除。有时出现的降植烷酸血症可能是由于饮食中的降植烷酸，而不是由于积累的植烷酸从头合成的降植烷酸。
