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. 1986 Aug;83(16):6156–6158. doi: 10.1073/pnas.83.16.6156

Biosynthesis and maturation of peroxisomal beta-oxidation enzymes in fibroblasts in relation to the Zellweger syndrome and infantile Refsum disease.

A W Schram, A Strijland, T Hashimoto, R J Wanders, R B Schutgens, H van den Bosch, J M Tager
PMCID: PMC386458  PMID: 2426710

Abstract

The biosynthesis of the peroxisomal enzymes acyl-CoA oxidase, 3-oxoacyl-CoA thiolase (acetyl-CoA acyl-transferase, EC 2.3.1.16), and catalase (EC 1.11.1.6) was studied in cultured skin fibroblasts from a control subject and from patients with Zellweger syndrome and the infantile form of Refsum disease, inherited disorders in which peroxisomes are deficient and certain peroxisomal functions are impaired. The results of continuous labeling and pulse-chase experiments indicate that in control fibroblasts, as in rat liver, acyl-CoA oxidase is synthesized as a 72-kDa percursor that is converted to two polypeptides of 52 and 20 kDa and 3-oxoacyl-CoA thiolase is synthesized as a 44-kDa precursor that is converted to the 41-kDa mature protein. In fibroblasts from the patients the precursors of the two enzymes are formed but their maturation is impaired, and they are rapidly degraded. In contrast, the biosynthesis of catalase is not impaired. We conclude that functional peroxisomes are required for the maturation and stability of acyl-CoA oxidase and 3-oxoacyl-CoA thiolase but not for catalase.

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Selected References

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  1. Arias J. A., Moser A. B., Goldfischer S. L. Ultrastructural and cytochemical demonstration of peroxisomes in cultured fibroblasts from patients with peroxisomal deficiency disorders. J Cell Biol. 1985 May;100(5):1789–1792. doi: 10.1083/jcb.100.5.1789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown F. R., 3rd, McAdams A. J., Cummins J. W., Konkol R., Singh I., Moser A. B., Moser H. W. Cerebro-hepato-renal (Zellweger) syndrome and neonatal adrenoleukodystrophy: similarities in phenotype and accumulation of very long chain fatty acids. Johns Hopkins Med J. 1982 Dec;151(6):344–351. [PubMed] [Google Scholar]
  3. Danks D. M., Tippett P., Adams C., Campbell P. Cerebro-hepato-renal syndrome of Zellweger. A report of eight cases with comments upon the incidence, the liver lesion, and a fault in pipecolic acid metabolism. J Pediatr. 1975 Mar;86(3):382–387. doi: 10.1016/s0022-3476(75)80967-x. [DOI] [PubMed] [Google Scholar]
  4. Datta N. S., Wilson G. N., Hajra A. K. Deficiency of enzymes catalyzing the biosynthesis of glycerol-ether lipids in Zellweger syndrome. A new category of metabolic disease involving the absence of peroxisomes. N Engl J Med. 1984 Oct 25;311(17):1080–1083. doi: 10.1056/NEJM198410253111704. [DOI] [PubMed] [Google Scholar]
  5. Eyssen H., Parmentier G., Compernolle F., Boon J., Eggermont E. Trihydroxycoprostanic acid in the duodenal fluid of two children with intrahepatic bile duct anomalies. Biochim Biophys Acta. 1972 Jun 26;273(1):212–221. doi: 10.1016/0304-4165(72)90209-7. [DOI] [PubMed] [Google Scholar]
  6. Fujiki Y., Rachubinski R. A., Mortensen R. M., Lazarow P. B. Synthesis of 3-ketoacyl-CoA thiolase of rat liver peroxisomes on free polyribosomes as a larger precursor. Induction of thiolase mRNA activity by clofibrate. Biochem J. 1985 Mar 15;226(3):697–704. doi: 10.1042/bj2260697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Furuta S., Hashimoto T., Miura S., Mori M., Tatibana M. Cell-free synthesis of the enzymes of peroxisomal beta-oxidation. Biochem Biophys Res Commun. 1982 Mar 30;105(2):639–646. doi: 10.1016/0006-291x(82)91482-6. [DOI] [PubMed] [Google Scholar]
  8. Goldfischer S., Moore C. L., Johnson A. B., Spiro A. J., Valsamis M. P., Wisniewski H. K., Ritch R. H., Norton W. T., Rapin I., Gartner L. M. Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome. Science. 1973 Oct 5;182(4107):62–64. doi: 10.1126/science.182.4107.62. [DOI] [PubMed] [Google Scholar]
  9. Goldman B. M., Blobel G. Biogenesis of peroxisomes: intracellular site of synthesis of catalase and uricase. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5066–5070. doi: 10.1073/pnas.75.10.5066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hajra A. K., Bishop J. E. Glycerolipid biosynthesis in peroxisomes via the acyl dihydroxyacetone phosphate pathway. Ann N Y Acad Sci. 1982;386:170–182. doi: 10.1111/j.1749-6632.1982.tb21415.x. [DOI] [PubMed] [Google Scholar]
  11. Heymans H. S., Schutgens R. B., Tan R., van den Bosch H., Borst P. Severe plasmalogen deficiency in tissues of infants without peroxisomes (Zellweger syndrome). Nature. 1983 Nov 3;306(5938):69–70. doi: 10.1038/306069a0. [DOI] [PubMed] [Google Scholar]
  12. Lazarow P. B., Black V., Shio H., Fujiki Y., Hajra A. K., Datta N. S., Bangaru B. S., Dancis J. Zellweger syndrome: biochemical and morphological studies on two patients treated with clofibrate. Pediatr Res. 1985 Dec;19(12):1356–1364. doi: 10.1203/00006450-198512000-00030. [DOI] [PubMed] [Google Scholar]
  13. Miura S., Mori M., Takiguchi M., Tatibana M., Furuta S., Miyazawa S., Hashimoto T. Biosynthesis and intracellular transport of enzymes of peroxisomal beta-oxidation. J Biol Chem. 1984 May 25;259(10):6397–6402. [PubMed] [Google Scholar]
  14. Miyazawa S., Furuta S., Osumi T., Hashimoto T., Ui N. Properties of peroxisomal 3-ketoacyl-coA thiolase from rat liver. J Biochem. 1981 Aug;90(2):511–519. doi: 10.1093/oxfordjournals.jbchem.a133499. [DOI] [PubMed] [Google Scholar]
  15. Ogier H., Roels F., Cornelis A., Poll The B. T., Scotto J. M., Odievre M., Sandubray J. M. Absence of hepatic peroxisomes in a case of infantile Refsum's disease. Scand J Clin Lab Invest. 1985 Dec;45(8):767–768. doi: 10.3109/00365518509155292. [DOI] [PubMed] [Google Scholar]
  16. Osumi T., Hashimoto T. Peroxisomal beta oxidation system of rat liver. Copurification of enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase. Biochem Biophys Res Commun. 1979 Jul 27;89(2):580–584. doi: 10.1016/0006-291x(79)90669-7. [DOI] [PubMed] [Google Scholar]
  17. Osumi T., Hashimoto T., Ui N. Purification and properties of acyl-CoA oxidase from rat liver. J Biochem. 1980 Jun;87(6):1735–1746. doi: 10.1093/oxfordjournals.jbchem.a132918. [DOI] [PubMed] [Google Scholar]
  18. Oude Elferink R. P., Strijland A., Surya I., Brouwer-Kelder E. M., Kroos M., Hilkens J., Hilgers J., Reuser A. J., Tager J. M. Use of a monoclonal antibody to distinguish between precursor and mature forms of human lysosomal alpha-glucosidase. Eur J Biochem. 1984 Mar 15;139(3):497–502. doi: 10.1111/j.1432-1033.1984.tb08033.x. [DOI] [PubMed] [Google Scholar]
  19. Pedersen J. I., Gustafsson J. Conversion of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid into cholic acid by rat liver peroxisomes. FEBS Lett. 1980 Dec 1;121(2):345–348. doi: 10.1016/0014-5793(80)80377-2. [DOI] [PubMed] [Google Scholar]
  20. Poulos A., Sharp P. Plasma and skin fibroblast C26 fatty acids in infantile Refsum's disease. Neurology. 1984 Dec;34(12):1606–1609. doi: 10.1212/wnl.34.12.1606. [DOI] [PubMed] [Google Scholar]
  21. Poulos A., Sharp P., Whiting M. Infantile Refsum's disease (phytanic acid storage disease): a variant of Zellweger's syndrome? Clin Genet. 1984 Dec;26(6):579–586. doi: 10.1111/j.1399-0004.1984.tb01107.x. [DOI] [PubMed] [Google Scholar]
  22. Poulos A., Whiting M. J. Identification of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid, an intermediate in cholic acid synthesis, in the plasma of patients with infantile Refsum's disease. J Inherit Metab Dis. 1985;8(1):13–17. doi: 10.1007/BF01805476. [DOI] [PubMed] [Google Scholar]
  23. Robbi M., Lazarow P. B. Synthesis of catalase in two cell-free protein-synthesizing systems and in rat liver. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4344–4348. doi: 10.1073/pnas.75.9.4344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Santos M. J., Ojeda J. M., Garrido J., Leighton F. Peroxisomal organization in normal and cerebrohepatorenal (Zellweger) syndrome fibroblasts. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6556–6560. doi: 10.1073/pnas.82.19.6556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schrakamp G., Roosenboom C. F., Schutgens R. B., Wanders R. J., Heymans H. S., Tager J. M., van den Bosch H. Alkyl dihydroxyacetone phosphate synthase in human fibroblasts and its deficiency in Zellweger syndrome. J Lipid Res. 1985 Jul;26(7):867–873. [PubMed] [Google Scholar]
  26. Schutgens R. B., Heymans H. S., Wanders R. J., van den Bosch H., Tager J. M. Peroxisomal disorders: a newly recognised group of genetic diseases. Eur J Pediatr. 1986 Feb;144(5):430–440. doi: 10.1007/BF00441734. [DOI] [PubMed] [Google Scholar]
  27. Schutgens R. B., Romeyn G. J., Wanders R. J., van den Bosch H., Schrakamp G., Heymans H. S. Deficiency of acyl-CoA: dihydroxyacetone phosphate acyltransferase in patients with Zellweger (cerebro-hepato-renal) syndrome. Biochem Biophys Res Commun. 1984 Apr 16;120(1):179–184. doi: 10.1016/0006-291x(84)91430-x. [DOI] [PubMed] [Google Scholar]
  28. Singh I., Moser A. E., Goldfischer S., Moser H. W. Lignoceric acid is oxidized in the peroxisome: implications for the Zellweger cerebro-hepato-renal syndrome and adrenoleukodystrophy. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4203–4207. doi: 10.1073/pnas.81.13.4203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Stokke O., Skrede S., Ek J., Björkhem I. Refsum's disease, adrenoleucodystrophy, and the Zellweger syndrome. Scand J Clin Lab Invest. 1984 Sep;44(5):463–464. doi: 10.3109/00365518409083839. [DOI] [PubMed] [Google Scholar]
  30. Tager J. M., Van der Beek W. A., Wanders R. J., Hashimoto T., Heymans H. S., Van den Bosch H., Schutgens R. B., Schram A. W. Peroxisomal beta-oxidation enzyme proteins in the Zellweger syndrome. Biochem Biophys Res Commun. 1985 Feb 15;126(3):1269–1275. doi: 10.1016/0006-291x(85)90322-5. [DOI] [PubMed] [Google Scholar]
  31. Wanders R. J., Kos M., Roest B., Meijer A. J., Schrakamp G., Heymans H. S., Tegelaers W. H., van den Bosch H., Schutgens R. B., Tager J. M. Activity of peroxisomal enzymes and intracellular distribution of catalase in Zellweger syndrome. Biochem Biophys Res Commun. 1984 Sep 28;123(3):1054–1061. doi: 10.1016/s0006-291x(84)80240-5. [DOI] [PubMed] [Google Scholar]
  32. Wanders R. J., Schutgens R. B., Tager J. M. Peroxisomal matrix enzymes in Zellweger syndrome: activity and subcellular localization in liver. J Inherit Metab Dis. 1985;8 (Suppl 2):151–152. doi: 10.1007/BF01811504. [DOI] [PubMed] [Google Scholar]

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