TY - JOUR
T1 - Peroxisomal very long-chain fatty acid β-oxidation in human skin fibroblasts
T2 - activity in Zellweger syndrome and other peroxisomal disorders
AU - Wanders, R. J.A.
AU - van Roermund, C. W.T.
AU - van Wijland, M. J.A.
AU - Heikoop, J.
AU - Schutgens, R. B.H.
AU - Schram, A. W.
AU - Tager, J. M.
AU - van den Bosch, H.
AU - Poll-Thé, B. T.
AU - Saudubray, J. M.
AU - Moser, H. W.
AU - Moser, A. B.
N1 - Funding Information:
This study was supported by grants from the Netherlands Organization for Pure Scientific Research (ZWO) under auspices of the Netherlands Foundation for Fundamental Medical Research (Medigon) and The Princess Beatrix Fund (The Hague, The Netherlands). Dr. J.A.J.M. Bakkeren is gratefully acknowledged for C26/C22_measurements. The authors wish to thank Paul Bentlage, Ellen Meyboom and Annie Van den Put for expert technical assistance and Anja Aaldering and Truus Klebach for typing the manuscript.
PY - 1987/7/15
Y1 - 1987/7/15
N2 - Since very long-chain fatty acids with a chain length of 24 carbons or more are known to accumulate in tissues and body fluids from patients with the cerebro-hepato-renal (Zellweger) syndrome, infantile Refsum disease, neonatal adrenoleukodystrophy and X-linked adrenoleukodystrophy, we studied very long-chain fatty acid oxidation in cultured skin fibroblasts from these patients. In this paper, we report that in accordance with earlier results the first step in the β-oxidation of the very long-chain fatty acid lignoceric acid (C24:0) primarily occurs in peroxisomes in control human skin fibroblasts. Furthermore, it was found that peroxisomal lignoceric acid β-oxidation was strongly deficient in fibroblasts from patients with Zellweger syndrome, infantile Refsum disease, neonatal and X-linked adrenoleukodystrophy, which explains for the accumulation of very long-chain fatty acids in all four disease entities. In Zellweger syndrome, infantile Refsum disease and neonatal adrenoleukodystrophy the impairment in peroxisomal very long-chain fatty acid β-oxidation is probably caused by a strong deficiency of all peroxisomal β-oxidation enzyme proteins due to a deficiency of peroxisomes.
AB - Since very long-chain fatty acids with a chain length of 24 carbons or more are known to accumulate in tissues and body fluids from patients with the cerebro-hepato-renal (Zellweger) syndrome, infantile Refsum disease, neonatal adrenoleukodystrophy and X-linked adrenoleukodystrophy, we studied very long-chain fatty acid oxidation in cultured skin fibroblasts from these patients. In this paper, we report that in accordance with earlier results the first step in the β-oxidation of the very long-chain fatty acid lignoceric acid (C24:0) primarily occurs in peroxisomes in control human skin fibroblasts. Furthermore, it was found that peroxisomal lignoceric acid β-oxidation was strongly deficient in fibroblasts from patients with Zellweger syndrome, infantile Refsum disease, neonatal and X-linked adrenoleukodystrophy, which explains for the accumulation of very long-chain fatty acids in all four disease entities. In Zellweger syndrome, infantile Refsum disease and neonatal adrenoleukodystrophy the impairment in peroxisomal very long-chain fatty acid β-oxidation is probably caused by a strong deficiency of all peroxisomal β-oxidation enzyme proteins due to a deficiency of peroxisomes.
KW - Adrenoleukodystrophy
KW - Peroxisomal β-oxidation
KW - Peroxisome
KW - Refsum disease
KW - Very long-chain fatty acid
KW - Zellweger syndrome
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U2 - 10.1016/0009-8981(87)90428-1
DO - 10.1016/0009-8981(87)90428-1
M3 - Article
C2 - 2441904
AN - SCOPUS:0023180287
SN - 0009-8981
VL - 166
SP - 255
EP - 263
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
IS - 2-3
ER -