Abstract
We have analyzed the phospholipid composition of various organs of patients with the cerebro-hepato-renal (Zellweger) syndrome. The phospholipid composition of tissues from controls and patients was very similar except for their plasmalogen contents. In controls about 50% of the phosphatidylethanolamine fraction of brain, heart, kidney and skeletal muscle and about 10% of that fraction in control liver tissue was found to consist of plasmalogen. In control heart muscle, but not in other control tissues about 25% of the phosphatidylcholine fraction consist of plasmalogens. In contrast, plasmalogens were nearly absent in the corresponding tissues of Zellweger patients.
The amount of phosphatidylethanolamine plasmalogens in both erythrocytes and fibroblasts of Zellweger patients is lowered significantly compared to control erythrocytes and control fibroblasts respectively, although this reduction is not as dramatic as in brain, heart, kidney, skeletal muscle and liver of patients. Phosphatidylcholine-plasmalogens are only present in low amounts in both controls, heterozygotes and patients.
In recent years considerable evidence has accumulated to show that peroxisomes are involved in cellular lipid metabolism. Notably, the key enzymes of ether lipid (plasmalogen) biosynthesis in rodents were recently found to be located in peroxisomes. Since electronmicroscopic studies have shown that peroxisomes are absent in liver and kidney of patients with the cerebro-hepato-renal syndrome, our results suggest that an inability to integrate these key enzymes in a functional peroxisome leads to a severe disturbance in plasmalogen biosynthesis.
We propose that the multiple clinical and biochemical defects in Zellweger patients are secondary to a deficiency in peroxisomal function.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arnold G, Holzman E (1978) Microperoxisomes in the central nervous system of the postnatal rat. Brain Res 155:1–17
Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917
Borst P (1983) Animal peroxisomes (microbodies), lipid biosynthesis and the Zellweger syndrome. Trends in Biochem Sci 8:269–272
Clarke NG, Dawson RMC (1981) A new method for the quantitative deacylation of phospholipids. Biochem J 195:301–306
Danks DM, Tippett P, Adams C, Campbell P (1975) Cerebrohepato-renal syndrome of Zellweger. J Pediatr 86:382–387
De Duve C (1983) Microbodies in the living cell. Scientific American, May: 52–62
De Duve C, Beaufay H, Jacques P, Rahman-Li Y, Sellinger OZ, Wattiaux R, de Coninck S (1960) Intracellular localization of catalase and of some oxidases in rat liver. Biochim Biophys Acta 40:186–187
Goldfischer S, Moore CL, Johnson AB, Spiro AJ, Valsamis MP, Wisniewski HK, Ritch RH, Norton WT, Rapin I, Gartner LM (1973) Peroxisomal and mitochondrial defects in the cerebrohepato-renal syndrome. Science 182:62–64
Govaerts L, Monnens L, Tegelaers W, Trijbels F, van Raay-Selten A (1982) Cerebro-hepato-renal syndrome of Zellweger: Clinical symptoms and relevant laboratory findings in 16 patients. Eur J Pediatr 139:125–128
Hajra AK, Bishop JE (1982) Glycerolipid biosynthesis in peroxisomes via the acyl dihydroxyacetone phosphate pathway. Ann NY Acad Sci 386:170–181
Hajra AK, Burke CL, Jones CL (1979) Subcellular localization of acylcoenzyme A: dihydroxyacetone phosphate acyltransferase in rat liver peroxisomes (microbodies). J Biol Chem 254: 10896–10900
Hanson RF, Szczepanik-van Leeuwen P, Williams GC, Grabowski G, Sharp HL (1979) Defects of bile acid synthesis in Zellweger's syndrome. Science 203:1107–1108
Horrocks LA (1968) The alk-1-enylgroup content of mammalian myelin phosphoglycerides by quantitative two-dimensional thinlayer chromatography. J Lipid Res 9:469–472
Lazarow PB (1978) Rat liver peroxisomes catalyze the β-oxidation of fatty acids. J Biol Chem 253:1522–1528
Lazarow PB (1982) Peroxisomes. In: Arias I, Popper H, Schachter D, Shafritz DA (eds) The liver: biology and pathobiology. Raven Press, New York, pp 27–39
Moody DE, Reddy JK (1976) Morphometric analysis of the ultrastructural changes in rat liver induced by the peroxisome proliferator Sa H42-348. J Cell Biol 71:786–790
Mooy WJ, Dingemans KP, Heymans HSA, vd Bergh Weerman MA, Jöbsis AC, Barth PG (1983) Ultrastructure of the liver in the cerebrohepatorenal syndrome of Zellweger. Ultrastruct Pathol (in press)
Moser HW, Brown FR, Moser AE, Kishimoto Y, Singh I (1983) Very long chain fatty acid oxidation in cerebro-hepato-renal (Zellweger's) syndrome and neonatal adrenoleukodystrophy. J Neurochem 41: abstract S25C
Müller-Höcker J, Bise K, Endres W, Hübner G (1981) Morphology and diagnosis of Zellweger syndrome. Virchows Arch 393: 103–114
Novikoff AB, Novikoff PM, Davis C, Quintana N (1973) Are microperoxisomes ubiquitous in mammalian cells? J Histochem Cytochem 21:737–755
Novikoff AB, Novikoff PM, Rosen OM, Rubin CS (1980) Organelle relationships in cultured 3T3-L1 preadipocytes. J Cell Biol 87:180–196
O'Brien JS, Sampson EL (1965) Lipid composition of the normal human brain: gray matter, white matter and myelin. J Lipid Res 6:537–544
Rouser G, Fleischer S, Jamamoto A (1970) Two dimensional thin-layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids 5:494–496
Ruitenbeek W (1978) The fatty acid composition of various lipid fractions isolated from erythrocytes and blood plasma of patients with Duchenne and congenital myotonic muscular dystrophy. Clin Chim Acta 89:99–110
Tolbert NE (1981) Metabolic pathways in peroxisomes and glyoxysomes. Ann Rev Biochem 50:133–157
Trijbels JMF, Berden JA, Monnens LAH, Willems JL, Jansen AJM, Schutgens RBH, vd Broek-van Essen M (1983) Biochemical studies in the liver and muscle of patients with Zellweger syndrome. Pediatr Res 17:514–517
Versmold HT, Bremer HJ, Herzog V, Siegel G, vBassewitz DB, Irle U, vVoss H, Lombeck I, Brauser B (1977) A metabolic disorder similar to Zellweger syndrome with hepatic acatalasia and absence of peroxisomes, altered content and redox state of cytochromes and infantile cirrhosis and hemosiderosis. Eur J Pediatr 124:261–275
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Heymans, H.S.A., Bosch, H.v.d., Schutgens, R.B.H. et al. Deficiency of plasmalogens in the cerebro-hepato-renal (Zellweger) syndrome. Eur J Pediatr 142, 10–15 (1984). https://doi.org/10.1007/BF00442582
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00442582