Hepatic peroxisomes are deficient in infantile refsum disease: A cytochemical study of 4 cases

Roels, Frank; Cornelis, Alfons; Bt, Poll-The; Aubourg, Patrick; Ogier, H.; Scotto, J; Jm, Saudubray

doi:10.1002/ajmg.1320250210

Cited by 98 publications

(55 citation statements)

References 47 publications

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“…Our experiments show that enhanced supply of phytol in the diet of mice is not destructive to peroxisomes. Actually, the number and size of peroxisomes is increased in liver and in several other organs, with a cytochemical picture contrasting to the situation observed in liver from infantile Refsum patients [15,16).…”

Section: Resultsmentioning

confidence: 94%

“…Mice fed a 5% phytol diet became ill sometimes after 3 or 4 days; they lose appetite, start shivering, and show the changes in the skin described by Klenk and Kremer (6). DISCUSSION Children with infantile Refsum's disease possess abnormal microbodies without catalase, or no microbodies at a11 (15,16). Whereas in the adult form of Refsum's disease the localization of the enzyme defect, i.e.…”

Section: Resultsmentioning

confidence: 99%

“…Cytochemistry and electron microscopy demonstrate the absence of normal peroxisomes in liver biopsies from these children (15,16). This finding and the presence of high levels of very long chain fatty acids and abnormal bile acid intermediates in infantile Refsum patients (17,18) indicate a link with two other neonatal "peroxisomal diseases," Zellweger's cerebrohepatorenal syndrome and adrenoleukodystrophy (autosomic recessive), in which peroxisomes are either absent or lacking several functions (I 9-24).…”

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Phytol and Peroxisome Proliferation

et al. 1986

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ABSTRACT. Infantile Refsum's disease is characterized by high levels of phytanic acid and the absence of normal hepatic peroxisomes. We investigated the in vivo influence of phytol, a precursor of phytanic acid, on peroxisomes by both biochemical and morphological methods. Enhanced supply of phytol in the diet of adult mice causes proliferation of hepatic peroxisomes. The peroxisomal &oxidizing capacity as well as exchanges of acyl moieties between peroxisomes and mitochondria are raised around 5-and 2-fold, respectively. In parallel a 1.5-fold increase of total catalase and mitochondria1 butyryl-CoA dehydrogenase activities occurs, whereas peroxisomal urate oxidase and glycolate oxidase remain normally active. Serum triglyceride levels are decreased after 3 wk of phytol feeding; serum cholesterol levels remain unaffected. Phytol feeding also induces peroxisome proliferation in duodenal epithelium, in myocardium and in skin sebaceous glands, but not in kidney. (Pediatr Res 20: 41 1-415, 1986)

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

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confidence: 98%

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Phytol and Peroxisome Proliferation

et al. 1986

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“…Studies in cultured skin fibroblasts have shown that peroxisomal fl-oxidation enzyme proteins are synthesized normally in Zellweger syndrome but are degraded rapidly due to the absence of peroxisomes (48). The same applies to infantile Refsum disease and neonatal adrenoleukodystrophy in which peroxisomes have also been shown to be strongly deficient in liver (32,(41)(42)(43)(44) and cultured fibroblasts (33,49).…”

Section: Discussionmentioning

confidence: 97%

Peroxisomal fatty acid beta-oxidation in relation to the accumulation of very long chain fatty acids in cultured skin fibroblasts from patients with Zellweger syndrome and other peroxisomal disorders.

Wanders¹,

Roermund²,

Wijland³

et al. 1987

J. Clin. Invest.

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The peroxisomal oxidation of the long chain fatty acid palmitate (C16:0) and the very long chain fatty acids lignocerate (C24:0) and cerotate (C26:0) was studied in freshly prepared homogenates of cultured skin fibroblasts from control individuals and patients with peroxisomal disorders. The peroxisomal oxidation of the fatty acids is almost completely dependent on the addition of ATP, coenzyme A (CoA), Mg2+ and NAD'.However, the dependency of the oxidation of palmitate on the concentration of the cofactors differs markedly from that of the oxidation of lignocerate and cerotate.The peroxisomal oxidation of all three fatty acid substrates is markedly deficient in fibroblasts from patients with the Zellweger syndrome, the neonatal form of adrenoleukodystrophy and the infantile form of Refsum disease, in accordance with the deficiency of peroxisomes in these patients. In fibroblasts from patients with X-linked adrenoleukodystrophy the peroxisomal oxidation of lignocerate and cerotate is impaired, but not that of palmitate. Competition experiments indicate that in fibroblasts, as in rat liver, distinct enzyme systems are responsible for the oxidation of palmitate on the one hand and lignocerate and cerotate on the other hand. Fractionation studies indicate that in rat liver activation of cerotate and lignocerate to cerotoyl-CoA and lignoceroyl-CoA, respectively, occurs in two subcellular fractions, the endoplasmic reticulum and the peroxisomes but not in the mitochondria. In homogenates of fibroblasts from patients lacking peroxisomes there is a small (25%) but significant deficiency of the ability to activate very long chain fatty acids. This deficient activity of very long chain fatty acyl-CoA synthetase is also observed in fibroblast homogenates from patients with X-linked adrenoleukodystrophy. We conclude that X-linked adrenoleukodystrophy is caused by a deficiency of peroxisomal very long chain fatty acyl-CoA synthetase.

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“…it is similar to that ohscrvcd in cytosol or in lgsosomcs fi-om livcr or other tissues of patients suflkr-ing koni pcroxisomal deficiency syndromes (1-ig. 0) and is classically believed to rcpresent very long-chain fit11 acid deposition (18)(19)(20)(21)(22). In the 0.…”

Section: Administrution To Mice Oj'u 05% Chlorpromuzine-c'ontuiningmentioning

confidence: 99%

Peroxisomal Proliferation in Heart and Liver of Mice Receiving Chlorpromazine, Ethyl 2(5(4-Chlorophenyl)Pentyl) Oxiran-2-Carboxylic Acid or High Fat Diet: A Biochemical and Morphometrical Comparative Study

et al. 1987

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Experiments with chlorpromazine, an inhibitor of peroxisomal carnitine octanoyltransferase, have led to the proposal that peroxisomal 0-oxidation which was depressed by the phenothiazine in isolated hepatocytes (1) was dependent on carnitine (2). On the other hand, the inhibition of both cytochrome c oxidase and chlorpromazine palmitoyltransferase activities (2) were proposed as the cause of the reduced ketone body formation from long-

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Hepatic peroxisomes are deficient in infantile refsum disease: A cytochemical study of 4 cases

Cited by 98 publications

References 47 publications

Phytol and Peroxisome Proliferation

Phytol and Peroxisome Proliferation

Peroxisomal fatty acid beta-oxidation in relation to the accumulation of very long chain fatty acids in cultured skin fibroblasts from patients with Zellweger syndrome and other peroxisomal disorders.

Peroxisomal Proliferation in Heart and Liver of Mice Receiving Chlorpromazine, Ethyl 2(5(4-Chlorophenyl)Pentyl) Oxiran-2-Carboxylic Acid or High Fat Diet: A Biochemical and Morphometrical Comparative Study

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