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Single Peroxisomal Enzyme and Transporter Deficiencies in Human Diseases and Mouse Models

  • Markus KunzeEmail author
  • Johannes BergerEmail author
Chapter

Abstract

Peroxisomal single enzyme and transporter deficiencies are inherited human diseases caused by the absence of individual enzymatic activities exerted in peroxisomes. These deficiencies either cause an abnormal accumulation of substances normally degraded in peroxisomes or the lack of biomolecules that require peroxisomal function for their synthesis. Consequently, the symptoms observed in diverse tissues of affected patients can be interpreted as consequences of metabolic intoxications or deficiencies in essential biomolecules. Thus, these detrimental effects should add-up to a very severe pathology upon concomitant inactivation of all peroxisomal functions, which is actually observed in patients suffering from peroxisome biogenesis disorders. Interestingly, only a subset of peroxisomal enzymes has been associated with single enzyme and transporter deficiencies and the inactivation of enzymes participating in the same metabolic pathway sometimes presents with drastically different phenotypical outcomes. Moreover, a remarkable spectrum of clinical pictures has been observed in human patients suffering from the same single enzyme deficiency. The utilization of mice lacking specifically one gene encoding for a peroxisomal enzyme (knockout-mice) allows the reduction of the broad spectrum of pathologies observed in human patients, because these mice are genetically very similar and live under standardized housing conditions. Thereby, these mice can serve as valuable tools to confirm biochemical outcomes of enzyme inactivation, to attribute specific phenotypic aberrations to the absence of an individual enzyme, and to test the contribution of exogenously added compounds to the development of certain symptoms.

Keywords

Single enzyme deficiencies Mouse models Peroxisomes Genotype Phenotype Environment Peroxisome biogenesis disorder Metabolism Fatty acid degradation 

Abbreviations

RCDP

Rhizomelic chondrodysplasia punctate

MRI

Magnetic resonance imaging

PAF

Platelet activating factor

PBD

Peroxisome biogenesis disorder

PUFA

Polyunsaturated fatty acid

VLCFA

Very long chain fatty acids

Notes

Acknowledgment

The authors thank Fabian Dorninger, Sonja Forss-Petter, and Christoph Wiesinger for helpful discussions and critically reading the manuscript and Christoph Wiesinger to provide Fig. 8.1.

References

  1. Agamanolis DP, Novak RW (1995) Rhizomelic chondrodysplasia punctata: report of a case with review of the literature and correlation with other peroxisomal disorders. Pediatr Pathol Lab Med 15(3):503–513PubMedGoogle Scholar
  2. Agrimi G, Russo A, Pierri CL, Palmieri F (2012) The peroxisomal NAD + carrier of Arabidopsis thaliana transports coenzyme A and its derivatives. J Bioenerg Biomembr 44(3):333–340. doi: 10.1007/s10863-012-9445-0 PubMedGoogle Scholar
  3. Amery L, Fransen M, De Nys K, Mannaerts GP, Van Veldhoven PP (2000) Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA racemase in humans. J Lipid Res 41(11):1752–1759PubMedGoogle Scholar
  4. Arnauld S, Fidaleo M, Clemencet MC, Chevillard G, Athias A, Gresti J, Wanders RJ, Latruffe N, Nicolas-Frances V, Mandard S (2009) Modulation of the hepatic fatty acid pool in peroxisomal 3-ketoacyl-CoA thiolase B-null mice exposed to the selective PPARalpha agonist Wy14,643. Biochimie 91(11–12):1376–1386. doi: 10.1016/j.biochi.2009.09.004 PubMedGoogle Scholar
  5. Ashibe B, Hirai T, Higashi K, Sekimizu K, Motojima K (2007) Dual subcellular localization in the endoplasmic reticulum and peroxisomes and a vital role in protecting against oxidative stress of fatty aldehyde dehydrogenase are achieved by alternative splicing. J Biol Chem 282(28):20763–20773. doi: 10.1074/jbc.M611853200 PubMedGoogle Scholar
  6. Atshaves BP, Payne HR, McIntosh AL, Tichy SE, Russell D, Kier AB, Schroeder F (2004) Sexually dimorphic metabolism of branched-chain lipids in C57BL/6J mice. J Lipid Res 45(5):812–830. doi: 10.1194/jlr.M300408-JLR200 PubMedGoogle Scholar
  7. Atshaves BP, McIntosh AL, Landrock D, Payne HR, Mackie JT, Maeda N, Ball J, Schroeder F, Kier AB (2007) Effect of SCP-x gene ablation on branched-chain fatty acid metabolism. Am J Physiol Gastrointest Liver Physiol 292(3):G939–G951. doi: 10.1152/ajpgi.00308.2006 PubMedGoogle Scholar
  8. Baes M, Van Veldhoven PP (2012) Mouse models for peroxisome biogenesis defects and beta-oxidation enzyme deficiencies. Biochim Biophys Acta 1822(9):1489–1500. doi: 10.1016/j.bbadis.2012.03.003 PubMedGoogle Scholar
  9. Baes M, Gressens P, Baumgart E, Carmeliet P, Casteels M, Fransen M, Evrard P, Fahimi D, Declercq PE, Collen D, van Veldhoven PP, Mannaerts GP (1997) A mouse model for Zellweger syndrome. Nat Genet 17(1):49–57. doi: 10.1038/ng0997-49 PubMedGoogle Scholar
  10. Baes M, Huyghe S, Carmeliet P, Declercq PE, Collen D, Mannaerts GP, Van Veldhoven PP (2000) Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl-branched fatty acids and bile acid intermediates but also of very long chain fatty acids. J Biol Chem 275(21):16329–16336. doi: 10.1074/jbc.M001994200 PubMedGoogle Scholar
  11. Baes M, Gressens P, Huyghe S, De NK, Qi C, Jia Y, Mannaerts GP, Evrard P, Van VP, Declercq PE, Reddy JK (2002) The neuronal migration defect in mice with Zellweger syndrome (Pex5 knockout) is not caused by the inactivity of peroxisomal beta-oxidation. J Neuropathol Exp Neurol 61(4):368–374PubMedGoogle Scholar
  12. Bams-Mengerink AM, Majoie CB, Duran M, Wanders RJ, Van Hove J, Scheurer CD, Barth PG, Poll-The BT (2006) MRI of the brain and cervical spinal cord in rhizomelic chondrodysplasia punctata. Neurology 66(6):798–803. doi: 10.1212/01.wnl.0000205594.34647.d0, discussion 789PubMedGoogle Scholar
  13. Beckers J, Wurst W, de Angelis MH (2009) Towards better mouse models: enhanced genotypes, systemic phenotyping and envirotype modelling. Nat Rev Genet 10(6):371–380. doi: 10.1038/nrg2578 PubMedGoogle Scholar
  14. Berger J, Gartner J (2006) X-linked adrenoleukodystrophy: clinical, biochemical and pathogenetic aspects. Biochim Biophys Acta 1763(12):1721–1732. doi: 10.1016/j.bbamcr.2006.07.010 PubMedGoogle Scholar
  15. Bernhardt K, Wilkinson S, Weber AP, Linka N (2012) A peroxisomal carrier delivers NAD(+) and contributes to optimal fatty acid degradation during storage oil mobilization. Plant J 69(1):1–13. doi: 10.1111/j.1365-313X.2011.04775.x PubMedGoogle Scholar
  16. Bösze P, Skripeczky K, Gaál M, Tóth A, László J (1983) Perrault’s syndrome in two sisters. Am J Med Genet 16(2):237–241PubMedGoogle Scholar
  17. Braverman NE, Moser AB (2012) Functions of plasmalogen lipids in health and disease. Biochim Biophys Acta 1822(9):1442–1452. doi: 10.1016/j.bbadis.2012.05.008 PubMedGoogle Scholar
  18. Braverman N, Steel G, Obie C, Moser A, Moser H, Gould SJ, Valle D (1997) Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. Nat Genet 15(4):369–376PubMedGoogle Scholar
  19. Breidenbach RW, Beevers H (1967) Association of the glyoxylate cycle enzymes in a novel subcellular particle from castor bean endosperm. Biochem Biophys Res Commun 27(4):462–469PubMedGoogle Scholar
  20. Brennemann W, Kohler W, Zierz S, Klingmuller D (1997) Testicular dysfunction in adrenomyeloneuropathy. Eur J Endocrinol 137(1):34–39PubMedGoogle Scholar
  21. Carlton VE, Harris BZ, Puffenberger EG, Batta AK, Knisely AS, Robinson DL, Strauss KA, Shneider BL, Lim WA, Salen G, Morton DH, Bull LN (2003) Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. Nat Genet 34(1):91–96. doi: 10.1038/ng1147 PubMedGoogle Scholar
  22. Cheng JB, Russell DW (2004) Mammalian wax biosynthesis. I. Identification of two fatty acyl-Coenzyme A reductases with different substrate specificities and tissue distributions. J Biol Chem 279(36):37789–37797. doi: 10.1074/jbc.M406225200 PubMedCentralPubMedGoogle Scholar
  23. Chevillard G, Clemencet MC, Latruffe N, Nicolas-Frances V (2004) Targeted disruption of the peroxisomal thiolase B gene in mouse: a new model to study disorders related to peroxisomal lipid metabolism. Biochimie 86(11):849–856. doi: 10.1016/j.biochi.2004.09.028 PubMedGoogle Scholar
  24. Clarke CE, Alger S, Preece MA, Burdon MA, Chavda S, Denis S, Ferdinandusse S, Wanders RJ (2004) Tremor and deep white matter changes in alpha-methylacyl-CoA racemase deficiency. Neurology 63(1):188–189PubMedGoogle Scholar
  25. Clayton PT, Lake BD, Hjelm M, Stephenson JB, Besley GT, Wanders RJ, Schram AW, Tager JM, Schutgens RB, Lawson AM (1988) Bile acid analyses in “pseudo-Zellweger” syndrome; clues to the defect in peroxisomal beta-oxidation. J Inherit Metab Dis 11(Suppl 2):165–168PubMedGoogle Scholar
  26. Danpure CJ (2004) Molecular aetiology of primary hyperoxaluria type 1. Nephron Exp Nephrol 98(2):e39–e44. doi: 10.1159/000080254 PubMedGoogle Scholar
  27. Danpure CJ, Jennings PR (1986) Peroxisomal alanine:glyoxylate aminotransferase deficiency in primary hyperoxaluria type I. FEBS Lett 201(1):20–24PubMedGoogle Scholar
  28. de Launoit Y, Adamski J (1999) Unique multifunctional HSD17B4 gene product: 17beta-hydroxysteroid dehydrogenase 4 and D-3-hydroxyacyl-coenzyme A dehydrogenase/hydratase involved in Zellweger syndrome. J Mol Endocrinol 22(3):227–240PubMedGoogle Scholar
  29. De Laurenzi V, Rogers GR, Hamrock DJ, Marekov LN, Steinert PM, Compton JG, Markova N, Rizzo WB (1996) Sjogren-Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene. Nat Genet 12(1):52–57. doi: 10.1038/ng0196-52 PubMedGoogle Scholar
  30. de Vet EC, Ijlst L, Oostheim W, Wanders RJ, van den Bosch H (1998) Alkyl-dihydroxyacetonephosphate synthase. Fate in peroxisome biogenesis disorders and identification of the point mutation underlying a single enzyme deficiency. J Biol Chem 273(17):10296–10301PubMedGoogle Scholar
  31. Dick D, Horvath R, Chinnery PF (2011) AMACR mutations cause late-onset autosomal recessive cerebellar ataxia. Neurology 76(20):1768–1770. doi: 10.1212/WNL.0b013e31821a4484 PubMedCentralPubMedGoogle Scholar
  32. Dodt G, Kim DG, Reimann SA, Reuber BE, McCabe K, Gould SJ, Mihalik SJ (2000) L-Pipecolic acid oxidase, a human enzyme essential for the degradation of L-pipecolic acid, is most similar to the monomeric sarcosine oxidases. Biochem J 345(Pt 3):487–494PubMedCentralPubMedGoogle Scholar
  33. Dommes V, Baumgart C, Kunau WH (1981) Degradation of unsaturated fatty acids in peroxisomes. Existence of a 2,4-dienoyl-CoA reductase pathway. J Biol Chem 256(16):8259–8262PubMedGoogle Scholar
  34. Dubey P, Raymond GV, Moser AB, Kharkar S, Bezman L, Moser HW (2005) Adrenal insufficiency in asymptomatic adrenoleukodystrophy patients identified by very long-chain fatty acid screening. J Pediatr 146(4):528–532. doi: 10.1016/j.jpeds.2004.10.067 PubMedGoogle Scholar
  35. El Hajj HI, Vluggens A, Andreoletti P, Ragot K, Mandard S, Kersten S, Waterham HR, Lizard G, Wanders RJ, Reddy JK, Cherkaoui-Malki M (2012) The inflammatory response in acyl-CoA oxidase 1 deficiency (pseudoneonatal adrenoleukodystrophy). Endocrinology 153(6):2568–2575. doi: 10.1210/en.2012-1137 PubMedCentralPubMedGoogle Scholar
  36. Engelen M, Schackmann MJ, Ofman R, Sanders RJ, Dijkstra IM, Houten SM, Fourcade S, Pujol A, Poll-The BT, Wanders RJ, Kemp S (2012) Bezafibrate lowers very long-chain fatty acids in X-linked adrenoleukodystrophy fibroblasts by inhibiting fatty acid elongation. J Inherit Metab Dis 35(6):1137–1145. doi: 10.1007/s10545-012-9471-4 PubMedCentralPubMedGoogle Scholar
  37. Facciotti F, Ramanjaneyulu GS, Lepore M, Sansano S, Cavallari M, Kistowska M, Forss-Petter S, Ni G, Colone A, Singhal A, Berger J, Xia C, Mori L, De Libero G (2012) Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus. Nat Immunol 13(5):474–480. doi: 10.1038/ni.2245 PubMedGoogle Scholar
  38. Fan CY, Pan J, Chu R, Lee D, Kluckman KD, Usuda N, Singh I, Yeldandi AV, Rao MS, Maeda N, Reddy JK (1996) Targeted disruption of the peroxisomal fatty acyl-CoA oxidase gene: generation of a mouse model of pseudoneonatal adrenoleukodystrophy. Ann N Y Acad Sci 804:530–541PubMedGoogle Scholar
  39. Fan CY, Pan J, Usuda N, Yeldandi AV, Rao MS, Reddy JK (1998) Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. Implications for peroxisome proliferator-activated receptor alpha natural ligand metabolism. J Biol Chem 273(25):15639–15645PubMedGoogle Scholar
  40. Ferdinandusse S, Mulders J, IJlst L, Denis S, Dacremont G, Waterham HR, Wanders RJ (1999) Molecular cloning and expression of human carnitine octanoyltransferase: evidence for its role in the peroxisomal beta-oxidation of branched-chain fatty acids. Biochem Biophys Res Commun 263(1):213–218. doi: 10.1006/bbrc.1999.1340 PubMedGoogle Scholar
  41. Ferdinandusse S, Denis S, Clayton PT, Graham A, Rees JE, Allen JT, McLean BN, Brown AY, Vreken P, Waterham HR, Wanders RJ (2000a) Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. Nat Genet 24(2):188–191. doi: 10.1038/72861 PubMedGoogle Scholar
  42. Ferdinandusse S, Denis S, IJlst L, Dacremont G, Waterham HR, Wanders RJ (2000b) Subcellular localization and physiological role of alpha-methylacyl-CoA racemase. J Lipid Res 41(11):1890–1896PubMedGoogle Scholar
  43. Ferdinandusse S, Denis S, van Berkel E, Dacremont G, Wanders RJ (2000c) Peroxisomal fatty acid oxidation disorders and 58 kDa sterol carrier protein X (SCPx). Activity measurements in liver and fibroblasts using a newly developed method. J Lipid Res 41(3):336–342PubMedGoogle Scholar
  44. Ferdinandusse S, Denis S, Mooijer PA, Zhang Z, Reddy JK, Spector AA, Wanders RJ (2001) Identification of the peroxisomal beta-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid. J Lipid Res 42(12):1987–1995PubMedGoogle Scholar
  45. Ferdinandusse S, Meissner T, Wanders RJ, Mayatepek E (2002a) Identification of the peroxisomal beta-oxidation enzymes involved in the degradation of leukotrienes. Biochem Biophys Res Commun 293(1):269–273. doi: 10.1016/S0006-291X(02)00214-0 PubMedGoogle Scholar
  46. Ferdinandusse S, Rusch H, van Lint AE, Dacremont G, Wanders RJ, Vreken P (2002b) Stereochemistry of the peroxisomal branched-chain fatty acid alpha- and beta-oxidation systems in patients suffering from different peroxisomal disorders. J Lipid Res 43(3):438–444PubMedGoogle Scholar
  47. Ferdinandusse S, van Grunsven EG, Oostheim W, Denis S, Hogenhout EM, IJlst L, van Roermund CW, Waterham HR, Goldfischer S, Wanders RJ (2002c) Reinvestigation of peroxisomal 3-ketoacyl-CoA thiolase deficiency: identification of the true defect at the level of d-bifunctional protein. Am J Hum Genet 70(6):1589–1593. doi: 10.1086/340970 PubMedCentralPubMedGoogle Scholar
  48. Ferdinandusse S, Denis S, Van Roermund CW, Wanders RJ, Dacremont G (2004) Identification of the peroxisomal beta-oxidation enzymes involved in the degradation of long-chain dicarboxylic acids. J Lipid Res 45(6):1104–1111. doi: 10.1194/jlr.M300512-JLR200 PubMedGoogle Scholar
  49. Ferdinandusse S, Denis S, Overmars H, Van Eeckhoudt L, Van Veldhoven PP, Duran M, Wanders RJ, Baes M (2005) Developmental changes of bile acid composition and conjugation in L- and D-bifunctional protein single and double knockout mice. J Biol Chem 280(19):18658–18666. doi: 10.1074/jbc.M414311200 PubMedGoogle Scholar
  50. Ferdinandusse S, Denis S, Mooyer PA, Dekker C, Duran M, Soorani-Lunsing RJ, Boltshauser E, Macaya A, Gartner J, Majoie CB, Barth PG, Wanders RJ, Poll-The BT (2006a) Clinical and biochemical spectrum of D-bifunctional protein deficiency. Ann Neurol 59(1):92–104. doi: 10.1002/ana.20702 PubMedGoogle Scholar
  51. Ferdinandusse S, Kostopoulos P, Denis S, Rusch H, Overmars H, Dillmann U, Reith W, Haas D, Wanders RJ, Duran M, Marziniak M (2006b) Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy. Am J Hum Genet 78(6):1046–1052. doi: 10.1086/503921 PubMedCentralPubMedGoogle Scholar
  52. Ferdinandusse S, Ylianttila MS, Gloerich J, Koski MK, Oostheim W, Waterham HR, Hiltunen JK, Wanders RJ, Glumoff T (2006c) Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis. Am J Hum Genet 78(1):112–124. doi: 10.1086/498880 PubMedCentralPubMedGoogle Scholar
  53. Ferdinandusse S, Denis S, Hogenhout EM, Koster J, van Roermund CW, IJlst L, Moser AB, Wanders RJ, Waterham HR (2007) Clinical, biochemical, and mutational spectrum of peroxisomal acyl-coenzyme A oxidase deficiency. Hum Mutat 28(9):904–912. doi: 10.1002/humu.20535 PubMedGoogle Scholar
  54. Ferdinandusse S, Zomer AW, Komen JC, van den Brink CE, Thanos M, Hamers FP, Wanders RJ, van der Saag PT, Poll-The BT, Brites P (2008) Ataxia with loss of Purkinje cells in a mouse model for Refsum disease. Proc Natl Acad Sci USA 105(46):17712–17717. doi: 10.1073/pnas.0806066105 PubMedCentralPubMedGoogle Scholar
  55. Ferdinandusse S, Barker S, Lachlan K, Duran M, Waterham HR, Wanders RJ, Hammans S (2010) Adult peroxisomal acyl-coenzyme A oxidase deficiency with cerebellar and brainstem atrophy. J Neurol Neurosurg Psychiatry 81(3):310–312. doi: 10.1136/jnnp.2009.176255 PubMedGoogle Scholar
  56. Ferrer I, Kapfhammer JP, Hindelang C, Kemp S, Troffer-Charlier N, Broccoli V, Callyzot N, Mooyer P, Selhorst J, Vreken P, Wanders RJ, Mandel JL, Pujol A (2005) Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum damage. Hum Mol Genet 14(23):3565–3577. doi: 10.1093/hmg/ddi384 PubMedGoogle Scholar
  57. Fidaleo M, Arnauld S, Clemencet MC, Chevillard G, Royer MC, De Bruycker M, Wanders RJ, Athias A, Gresti J, Clouet P, Degrace P, Kersten S, Espeel M, Latruffe N, Nicolas-Frances V, Mandard S (2011) A role for the peroxisomal 3-ketoacyl-CoA thiolase B enzyme in the control of PPARalpha-mediated upregulation of SREBP-2 target genes in the liver. Biochimie 93(5):876–891. doi: 10.1016/j.biochi.2011.02.001 PubMedGoogle Scholar
  58. Filppula SA, Yagi AI, Kilpelainen SH, Novikov D, FitzPatrick DR, Vihinen M, Valle D, Hiltunen JK (1998) Delta3,5-delta2,4-dienoyl-CoA isomerase from rat liver. Molecular characterization. J Biol Chem 273(1):349–355PubMedGoogle Scholar
  59. Forss-Petter S, Werner H, Berger J, Lassmann H, Molzer B, Schwab MH, Bernheimer H, Zimmermann F, Nave KA (1997) Targeted inactivation of the X-linked adrenoleukodystrophy gene in mice. J Neurosci Res 50(5):829–843PubMedGoogle Scholar
  60. Foulon V, Antonenkov VD, Croes K, Waelkens E, Mannaerts GP, Van Veldhoven PP, Casteels M (1999) Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids. Proc Natl Acad Sci USA 96(18):10039–10044PubMedCentralPubMedGoogle Scholar
  61. Fourcade S, Lopez-Erauskin J, Galino J, Duval C, Naudi A, Jove M, Kemp S, Villarroya F, Ferrer I, Pamplona R, Portero-Otin M, Pujol A (2008) Early oxidative damage underlying neurodegeneration in X-adrenoleukodystrophy. Hum Mol Genet 17(12):1762–1773. doi: 10.1093/hmg/ddn085 PubMedGoogle Scholar
  62. Geisbrecht BV, Zhang D, Schulz H, Gould SJ (1999) Characterization of PECI, a novel monofunctional Delta(3), Delta(2)-enoyl-CoA isomerase of mammalian peroxisomes. J Biol Chem 274(31):21797–21803PubMedGoogle Scholar
  63. Glaser PE, Gross RW (1995) Rapid plasmenylethanolamine-selective fusion of membrane bilayers catalyzed by an isoform of glyceraldehyde-3-phosphate dehydrogenase: discrimination between glycolytic and fusogenic roles of individual isoforms. Biochemistry 34(38):12193–12203PubMedGoogle Scholar
  64. Gloerich J, Ruiter JP, van den Brink DM, Ofman R, Ferdinandusse S, Wanders RJ (2006) Peroxisomal trans-2-enoyl-CoA reductase is involved in phytol degradation. FEBS Lett 580(8):2092–2096. doi: 10.1016/j.febslet.2006.03.011 PubMedGoogle Scholar
  65. Goth L, Rass P, Pay A (2004) Catalase enzyme mutations and their association with diseases. Mol Diagn 8(3):141–149PubMedGoogle Scholar
  66. Gronemeyer T, Wiese S, Ofman R, Bunse C, Pawlas M, Hayen H, Eisenacher M, Stephan C, Meyer HE, Waterham HR, Erdmann R, Wanders RJ, Warscheid B (2013) The proteome of human liver peroxisomes: identification of five new peroxisomal constituents by a label-free quantitative proteomics survey. PLoS One 8(2):e57395. doi: 10.1371/journal.pone.0057395 PubMedCentralPubMedGoogle Scholar
  67. Hajra AK (1997) Dihydroxyacetone phosphate acyltransferase. Biochim Biophys Acta 1348(1–2):27–34PubMedGoogle Scholar
  68. Hashimoto T, Fujita T, Usuda N, Cook W, Qi C, Peters JM, Gonzalez FJ, Yeldandi AV, Rao MS, Reddy JK (1999) Peroxisomal and mitochondrial fatty acid beta-oxidation in mice nullizygous for both peroxisome proliferator-activated receptor alpha and peroxisomal fatty acyl-CoA oxidase. Genotype correlation with fatty liver phenotype. J Biol Chem 274(27):19228–19236PubMedGoogle Scholar
  69. Hashimoto T, Cook WS, Qi C, Yeldandi AV, Reddy JK, Rao MS (2000) Defect in peroxisome proliferator-activated receptor alpha-inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting. J Biol Chem 275(37):28918–28928. doi: 10.1074/jbc.M910350199 PubMedGoogle Scholar
  70. Haugarvoll K, Johansson S, Tzoulis C, Haukanes BI, Bredrup C, Neckelmann G, Boman H, Knappskog PM, Bindoff LA (2013) MRI characterisation of adult onset alpha-methylacyl-coA racemase deficiency diagnosed by exome sequencing. Orphanet J Rare Dis 8:1. doi: 10.1186/1750-1172-8-1 PubMedCentralPubMedGoogle Scholar
  71. Ho YS, Xiong Y, Ma W, Spector A, Ho DS (2004) Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem 279(31):32804–32812. doi: 10.1074/jbc.M404800200 PubMedGoogle Scholar
  72. Hoppe B (2012) An update on primary hyperoxaluria. Nat Rev Nephrol 8(8):467–475. doi: 10.1038/nrneph.2012.113 PubMedGoogle Scholar
  73. Houten SM, Denis S, Argmann CA, Jia Y, Ferdinandusse S, Reddy JK, Wanders RJ (2012) Peroxisomal L-bifunctional enzyme (Ehhadh) is essential for the production of medium-chain dicarboxylic acids. J Lipid Res 53(7):1296–1303. doi: 10.1194/jlr.M024463 PubMedCentralPubMedGoogle Scholar
  74. Huang J, Viswakarma N, Yu S, Jia Y, Bai L, Vluggens A, Cherkaoui-Malki M, Khan M, Singh I, Yang G, Rao MS, Borensztajn J, Reddy JK (2011) Progressive endoplasmic reticulum stress contributes to hepatocarcinogenesis in fatty acyl-CoA oxidase 1-deficient mice. Am J Pathol 179(2):703–713. doi: 10.1016/j.ajpath.2011.04.030 PubMedCentralPubMedGoogle Scholar
  75. Huang J, Jia Y, Fu T, Viswakarma N, Bai L, Rao MS, Zhu Y, Borensztajn J, Reddy JK (2012) Sustained activation of PPARalpha by endogenous ligands increases hepatic fatty acid oxidation and prevents obesity in ob/ob mice. FASEB J 26(2):628–638. doi: 10.1096/fj.11-194019 PubMedCentralPubMedGoogle Scholar
  76. Huffnagel IC, Clur SA, Bams-Mengerink AM, Blom NA, Wanders RJ, Waterham HR, Poll-The BT (2013) Rhizomelic chondrodysplasia punctata and cardiac pathology. J Med Genet 50(7):419–424. doi: 10.1136/jmedgenet-2013-101536 PubMedGoogle Scholar
  77. Hungerbuhler JP, Meier C, Rousselle L, Quadri P, Bogousslavsky J (1985) Refsum’s disease: management by diet and plasmapheresis. Eur Neurol 24(3):153–159PubMedGoogle Scholar
  78. Huyghe S, Casteels M, Janssen A, Meulders L, Mannaerts GP, Declercq PE, Van Veldhoven PP, Baes M (2001) Prenatal and postnatal development of peroxisomal lipid-metabolizing pathways in the mouse. Biochem J 353(Pt 3):673–680PubMedCentralPubMedGoogle Scholar
  79. Huyghe S, Schmalbruch H, De Gendt K, Verhoeven G, Guillou F, Van Veldhoven PP, Baes M (2006a) Peroxisomal multifunctional protein 2 is essential for lipid homeostasis in Sertoli cells and male fertility in mice. Endocrinology 147(5):2228–2236. doi: 10.1210/en.2005-1571 PubMedGoogle Scholar
  80. Huyghe S, Schmalbruch H, Hulshagen L, Veldhoven PV, Baes M, Hartmann D (2006b) Peroxisomal multifunctional protein-2 deficiency causes motor deficits and glial lesions in the adult central nervous system. Am J Pathol 168(4):1321–1334. doi: 10.2353/ajpath.2006.041220 PubMedCentralPubMedGoogle Scholar
  81. Hwang I, Lee J, Huh JY, Park J, Lee HB, Ho YS, Ha H (2012) Catalase deficiency accelerates diabetic renal injury through peroxisomal dysfunction. Diabetes 61(3):728–738. doi: 10.2337/db11-0584 PubMedCentralPubMedGoogle Scholar
  82. Ijlst L, de Kromme I, Oostheim W, Wanders RJ (2000) Molecular cloning and expression of human L-pipecolate oxidase. Biochem Biophys Res Commun 270(3):1101–1105. doi: 10.1006/bbrc.2000.2575 PubMedGoogle Scholar
  83. Jansen GA, Wanders RJ, Watkins PA, Mihalik SJ (1997) Phytanoyl-coenzyme A hydroxylase deficiency—the enzyme defect in Refsum‘s disease. N Engl J Med 337(2):133–134. doi: 10.1056/NEJM199707103370215 PubMedGoogle Scholar
  84. Jansen GA, van den Brink DM, Ofman R, Draghici O, Dacremont G, Wanders RJ (2001) Identification of pristanal dehydrogenase activity in peroxisomes: conclusive evidence that the complete phytanic acid alpha-oxidation pathway is localized in peroxisomes. Biochem Biophys Res Commun 283(3):674–679. doi: 10.1006/bbrc.2001.4835 PubMedGoogle Scholar
  85. Jansen GA, Waterham HR, Wanders RJ (2004) Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). Hum Mutat 23(3):209–218. doi: 10.1002/humu.10315 PubMedGoogle Scholar
  86. Jia Y, Qi C, Zhang Z, Hashimoto T, Rao MS, Huyghe S, Suzuki Y, Van Veldhoven PP, Baes M, Reddy JK (2003) Overexpression of peroxisome proliferator-activated receptor-alpha (PPARalpha)-regulated genes in liver in the absence of peroxisome proliferation in mice deficient in both L- and D-forms of enoyl-CoA hydratase/dehydrogenase enzymes of peroxisomal beta-oxidation system. J Biol Chem 278(47):47232–47239. doi: 10.1074/jbc.M306363200 PubMedGoogle Scholar
  87. Johnson MR, Barnes S, Kwakye JB, Diasio RB (1991) Purification and characterization of bile acid-CoA:amino acid N-acyltransferase from human liver. J Biol Chem 266(16):10227–10233PubMedGoogle Scholar
  88. Jones JM, Morrell JC, Gould SJ (2000) Identification and characterization of HAOX1, HAOX2, and HAOX3, three human peroxisomal 2-hydroxy acid oxidases. J Biol Chem 275(17):12590–12597PubMedGoogle Scholar
  89. Kanzawa N, Maeda Y, Ogiso H, Murakami Y, Taguchi R, Kinoshita T (2009) Peroxisome dependency of alkyl-containing GPI-anchor biosynthesis in the endoplasmic reticulum. Proc Natl Acad Sci USA 106(42):17711–17716. doi: 10.1073/pnas.0904762106 PubMedCentralPubMedGoogle Scholar
  90. Kapina V, Sedel F, Truffert A, Horvath J, Wanders RJ, Waterham HR, Picard F (2010) Relapsing rhabdomyolysis due to peroxisomal alpha-methylacyl-coa racemase deficiency. Neurology 75(14):1300–1302. doi: 10.1212/WNL.0b013e3181f612a5 PubMedGoogle Scholar
  91. Kisaki T, Tolbert NE (1969) Glycolate and glyoxylate metabolism by isolated peroxisomes or chloroplasts. Plant Physiol 44(2):242–250PubMedCentralPubMedGoogle Scholar
  92. Knight J, Jiang J, Assimos DG, Holmes RP (2006) Hydroxyproline ingestion and urinary oxalate and glycolate excretion. Kidney Int 70(11):1929–1934. doi: 10.1038/sj.ki.5001906 PubMedCentralPubMedGoogle Scholar
  93. Knight J, Holmes RP, Cramer SD, Takayama T, Salido E (2012) Hydroxyproline metabolism in mouse models of primary hyperoxaluria. Am J Physiol Renal Physiol 302(6):F688–F693. doi: 10.1152/ajprenal.00473.2011 PubMedCentralPubMedGoogle Scholar
  94. Kobayashi T, Shinnoh N, Kondo A, Yamada T (1997) Adrenoleukodystrophy protein-deficient mice represent abnormality of very long chain fatty acid metabolism. Biochem Biophys Res Commun 232(3):631–636. doi: 10.1006/bbrc.1997.6340 PubMedGoogle Scholar
  95. Kobayashi M, Sugiyama H, Wang DH, Toda N, Maeshima Y, Yamasaki Y, Masuoka N, Yamada M, Kira S, Makino H (2005) Catalase deficiency renders remnant kidneys more susceptible to oxidant tissue injury and renal fibrosis in mice. Kidney Int 68(3):1018–1031. doi: 10.1111/j.1523-1755.2005.00494.x PubMedGoogle Scholar
  96. Kodama S, Nishio H, Nakajima T, Nakamura H (1990) Urinary dicarboxylic acids in X-linked adrenoleukodystrophy. Acta Paediatr Jpn 32(3):257–261, Overseas editionPubMedGoogle Scholar
  97. Komljenovic D, Sandhoff R, Teigler A, Heid H, Just WW, Gorgas K (2009) Disruption of blood-testis barrier dynamics in ether-lipid-deficient mice. Cell Tissue Res 337(2):281–299. doi: 10.1007/s00441-009-0809-7 PubMedGoogle Scholar
  98. Kotti TJ, Savolainen K, Helander HM, Yagi A, Novikov DK, Kalkkinen N, Conzelmann E, Hiltunen JK, Schmitz W (2000) In mouse alpha -methylacyl-CoA racemase, the same gene product is simultaneously located in mitochondria and peroxisomes. J Biol Chem 275(27):20887–20895. doi: 10.1074/jbc.M002067200 PubMedGoogle Scholar
  99. Krysko O, Bottelbergs A, Van Veldhoven P, Baes M (2010) Combined deficiency of peroxisomal beta-oxidation and ether lipid synthesis in mice causes only minor cortical neuronal migration defects but severe hypotonia. Mol Genet Metab 100(1):71–76. doi: 10.1016/j.ymgme.2010.02.003 PubMedGoogle Scholar
  100. Leumann E, Hoppe B (2001) The primary hyperoxalurias. J Am Soc Nephrol 12(9):1986–1993PubMedGoogle Scholar
  101. Liegel R, Chang B, Dubielzig R, Sidjanin DJ (2011) Blind sterile 2 (bs2), a hypomorphic mutation in Agps, results in cataracts and male sterility in mice. Mol Genet Metab 103(1):51–59. doi: 10.1016/j.ymgme.2011.02.002 PubMedCentralPubMedGoogle Scholar
  102. Lopez-Erauskin J, Fourcade S, Galino J, Ruiz M, Schluter A, Naudi A, Jove M, Portero-Otin M, Pamplona R, Ferrer I, Pujol A (2011) Antioxidants halt axonal degeneration in a mouse model of X-adrenoleukodystrophy. Ann Neurol 70(1):84–92. doi: 10.1002/ana.22363 PubMedCentralPubMedGoogle Scholar
  103. Lu JF, Lawler AM, Watkins PA, Powers JM, Moser AB, Moser HW, Smith KD (1997) A mouse model for X-linked adrenoleukodystrophy. Proc Natl Acad Sci USA 94(17):9366–9371PubMedCentralPubMedGoogle Scholar
  104. Martens K, Loren V, van Themaat E, van Batenburg MF, Heinaniemi M, Huyghe S, Van Hummelen P, Carlberg C, Van Veldhoven PP, Van Kampen A, Baes M (2008) Coordinate induction of PPAR alpha and SREBP2 in multifunctional protein 2 deficient mice. Biochim Biophys Acta 1781(11–12):694–702. doi: 10.1016/j.bbalip.2008.07.010 PubMedGoogle Scholar
  105. Mihalik SJ, Moser HW, Watkins PA, Danks DM, Poulos A, Rhead WJ (1989) Peroxisomal L-pipecolic acid oxidation is deficient in liver from Zellweger syndrome patients. Pediatr Res 25(5):548–552. doi: 10.1203/00006450-198905000-00024 PubMedGoogle Scholar
  106. Mihalik SJ, Rainville AM, Watkins PA (1995) Phytanic acid alpha-oxidation in rat liver peroxisomes. Production of alpha-hydroxyphytanoyl-CoA and formate is enhanced by dioxygenase cofactors. Eur J Biochem 232(2):545–551PubMedGoogle Scholar
  107. Mihalik SJ, Morrell JC, Kim D, Sacksteder KA, Watkins PA, Gould SJ (1997) Identification of PAHX, a Refsum disease gene. Nat Genet 17(2):185–189. doi: 10.1038/ng1097-185 PubMedGoogle Scholar
  108. Mitchell J, Paul P, Chen HJ, Morris A, Payling M, Falchi M, Habgood J, Panoutsou S, Winkler S, Tisato V, Hajitou A, Smith B, Vance C, Shaw C, Mazarakis ND, de Belleroche J (2010) Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase. Proc Natl Acad Sci USA 107(16):7556–7561. doi: 10.1073/pnas.0914128107 PubMedCentralPubMedGoogle Scholar
  109. Mizumoto H, Akashi R, Hikita N, Kumakura A, Yoshida Y, Honda A, Shimozawa N, Hata D (2012) Mild case of D-bifunctional protein deficiency associated with novel gene mutations. Pediatr Int 54(2):303–304. doi: 10.1111/j.1442-200X.2012.03562.x PubMedGoogle Scholar
  110. Morita M, Imanaka T (2012) Peroxisomal ABC transporters: structure, function and role in disease. Biochim Biophys Acta 1822(9):1387–1396. doi: 10.1016/j.bbadis.2012.02.009 PubMedGoogle Scholar
  111. Mosser J, Douar AM, Sarde CO, Kioschis P, Feil R, Moser H, Poustka AM, Mandel JL, Aubourg P (1993) Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature 361(6414):726–730. doi: 10.1038/361726a0 PubMedGoogle Scholar
  112. Netik A, Forss-Petter S, Holzinger A, Molzer B, Unterrainer G, Berger J (1999) Adrenoleukodystrophy-related protein can compensate functionally for adrenoleukodystrophy protein deficiency (X-ALD): implications for therapy. Hum Mol Genet 8(5):907–913PubMedGoogle Scholar
  113. Nguyen SD, Baes M, Van Veldhoven PP (2008) Degradation of very long chain dicarboxylic polyunsaturated fatty acids in mouse hepatocytes, a peroxisomal process. Biochim Biophys Acta 1781(8):400–405. doi: 10.1016/j.bbalip.2008.06.004 PubMedGoogle Scholar
  114. Ofman R, Hettema EH, Hogenhout EM, Caruso U, Muijsers AO, Wanders RJ (1998) Acyl-CoA:dihydroxyacetonephosphate acyltransferase: cloning of the human cDNA and resolution of the molecular basis in rhizomelic chondrodysplasia punctata type 2. Hum Mol Genet 7(5):847–853PubMedGoogle Scholar
  115. Ogata M (1991) Acatalasemia. Hum Genet 86(4):331–340PubMedGoogle Scholar
  116. Ohide H, Miyoshi Y, Maruyama R, Hamase K, Konno R (2011) D-Amino acid metabolism in mammals: biosynthesis, degradation and analytical aspects of the metabolic study. J Chromatogr B Anal Technol Biomed Life Sci 879(29):3162–3168. doi: 10.1016/j.jchromb.2011.06.028 Google Scholar
  117. Oliet SH, Mothet JP (2009) Regulation of N-methyl-D-aspartate receptors by astrocytic D-serine. Neuroscience 158(1):275–283. doi: 10.1016/j.neuroscience.2008.01.071 PubMedGoogle Scholar
  118. Perrault M, Klotz B, Housset E (1951) Deux cas de syndrome de Turner avec surdi-mutite dans une meme fratrie. Bull Mem Soc Med Hop Paris 16:79–84, http://www.ncbi.nlm.nih.gov/pubmed/6650568 Google Scholar
  119. Pierce SB, Walsh T, Chisholm KM, Lee MK, Thornton AM, Fiumara A, Opitz JM, Levy-Lahad E, Klevit RE, King MC (2010) Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. Am J Hum Genet 87(2):282–288. doi: 10.1016/j.ajhg.2010.07.007 PubMedCentralPubMedGoogle Scholar
  120. Pike LJ, Han X, Chung KN, Gross RW (2002) Lipid rafts are enriched in arachidonic acid and plasmenylethanolamine and their composition is independent of caveolin-1 expression: a quantitative electrospray ionization/mass spectrometric analysis. Biochemistry 41(6):2075–2088PubMedGoogle Scholar
  121. Poll-The BT, Gartner J (2012) Clinical diagnosis, biochemical findings and MRI spectrum of peroxisomal disorders. Biochim Biophys Acta 1822(9):1421–1429. doi: 10.1016/j.bbadis.2012.03.011 PubMedGoogle Scholar
  122. Poll-The BT, Roels F, Ogier H, Scotto J, Vamecq J, Schutgens RB, Wanders RJ, van Roermund CW, van Wijland MJ, Schram AW et al (1988) A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy). Am J Hum Genet 42(3):422–434PubMedCentralPubMedGoogle Scholar
  123. Powers JM, Kenjarski TP, Moser AB, Moser HW (1999) Cerebellar atrophy in chronic rhizomelic chondrodysplasia punctata: a potential role for phytanic acid and calcium in the death of its Purkinje cells. Acta Neuropathol 98(2):129–134PubMedGoogle Scholar
  124. Powers JM, DeCiero DP, Ito M, Moser AB, Moser HW (2000) Adrenomyeloneuropathy: a neuropathologic review featuring its noninflammatory myelopathy. J Neuropathol Exp Neurol 59(2):89–102PubMedGoogle Scholar
  125. Pujol A, Hindelang C, Callizot N, Bartsch U, Schachner M, Mandel JL (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum Mol Genet 11(5):499–505PubMedGoogle Scholar
  126. Pujol A, Ferrer I, Camps C, Metzger E, Hindelang C, Callizot N, Ruiz M, Pampols T, Giros M, Mandel JL (2004) Functional overlap between ABCD1 (ALD) and ABCD2 (ALDR) transporters: a therapeutic target for X-adrenoleukodystrophy. Hum Mol Genet 13(23):2997–3006. doi: 10.1093/hmg/ddh323 PubMedGoogle Scholar
  127. Qi C, Zhu Y, Pan J, Usuda N, Maeda N, Yeldandi AV, Rao MS, Hashimoto T, Reddy JK (1999) Absence of spontaneous peroxisome proliferation in enoyl-CoA Hydratase/L-3-hydroxyacyl-CoA dehydrogenase-deficient mouse liver. Further support for the role of fatty acyl CoA oxidase in PPARalpha ligand metabolism. J Biol Chem 274(22):15775–15780PubMedGoogle Scholar
  128. Rizzo C, Boenzi S, Wanders RJ, Duran M, Caruso U, Dionisi-Vici C (2003) Characteristic acylcarnitine profiles in inherited defects of peroxisome biogenesis: a novel tool for screening diagnosis using tandem mass spectrometry. Pediatr Res 53(6):1013–1018PubMedGoogle Scholar
  129. Rodemer C, Thai TP, Brugger B, Kaercher T, Werner H, Nave KA, Wieland F, Gorgas K, Just WW (2003) Inactivation of ether lipid biosynthesis causes male infertility, defects in eye development and optic nerve hypoplasia in mice. Hum Mol Genet 12(15):1881–1895PubMedGoogle Scholar
  130. Rokka A, Antonenkov VD, Soininen R, Immonen HL, Pirila PL, Bergmann U, Sormunen RT, Weckstrom M, Benz R, Hiltunen JK (2009) Pxmp2 is a channel-forming protein in Mammalian peroxisomal membrane. PLoS One 4(4):e5090. doi: 10.1371/journal.pone.0005090 PubMedCentralPubMedGoogle Scholar
  131. Ruether K, Baldwin E, Casteels M, Feher MD, Horn M, Kuranoff S, Leroy BP, Wanders RJ, Wierzbicki AS (2010) Adult Refsum disease: a form of tapetoretinal dystrophy accessible to therapy. Surv Ophthalmol 55(6):531–538. doi: 10.1016/j.survophthal.2010.03.007 PubMedGoogle Scholar
  132. Salido EC, Li XM, Lu Y, Wang X, Santana A, Roy-Chowdhury N, Torres A, Shapiro LJ, Roy-Chowdhury J (2006) Alanine-glyoxylate aminotransferase-deficient mice, a model for primary hyperoxaluria that responds to adenoviral gene transfer. Proc Natl Acad Sci USA 103(48):18249–18254. doi: 10.1073/pnas.0607218103 PubMedCentralPubMedGoogle Scholar
  133. Salido E, Pey AL, Rodriguez R, Lorenzo V (2012) Primary hyperoxalurias: disorders of glyoxylate detoxification. Biochim Biophys Acta 1822(9):1453–1464. doi: 10.1016/j.bbadis.2012.03.004 PubMedGoogle Scholar
  134. Sasabe J, Chiba T, Yamada M, Okamoto K, Nishimoto I, Matsuoka M, Aiso S (2007) D-serine is a key determinant of glutamate toxicity in amyotrophic lateral sclerosis. EMBO J 26(18):4149–4159. doi: 10.1038/sj.emboj.7601840 PubMedCentralPubMedGoogle Scholar
  135. Sasabe J, Miyoshi Y, Suzuki M, Mita M, Konno R, Matsuoka M, Hamase K, Aiso S (2012) D-amino acid oxidase controls motoneuron degeneration through D-serine. Proc Natl Acad Sci USA 109(2):627–632. doi: 10.1073/pnas.1114639109 PubMedCentralPubMedGoogle Scholar
  136. Savolainen K, Kotti TJ, Schmitz W, Savolainen TI, Sormunen RT, Ilves M, Vainio SJ, Conzelmann E, Hiltunen JK (2004) A mouse model for alpha-methylacyl-CoA racemase deficiency: adjustment of bile acid synthesis and intolerance to dietary methyl-branched lipids. Hum Mol Genet 13(9):955–965. doi: 10.1093/hmg/ddh107 PubMedGoogle Scholar
  137. Schram AW, Goldfischer S, van Roermund CW, Brouwer-Kelder EM, Collins J, Hashimoto T, Heymans HS, van den Bosch H, Schutgens RB, Tager JM et al (1987) Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. Proc Natl Acad Sci USA 84(8):2494–2496PubMedCentralPubMedGoogle Scholar
  138. Seedorf U, Raabe M, Ellinghaus P, Kannenberg F, Fobker M, Engel T, Denis S, Wouters F, Wirtz KW, Wanders RJ, Maeda N, Assmann G (1998) Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function. Genes Dev 12(8):1189–1201PubMedCentralPubMedGoogle Scholar
  139. Selkala EM, Kuusisto SM, Salonurmi T, Savolainen MJ, Jauhiainen M, Pirila PL, Kvist AP, Conzelmann E, Schmitz W, Alexson SE, Kotti TJ, Hiltunen JK, Autio KJ (2013) Metabolic adaptation allows Amacr-deficient mice to remain symptom-free despite low levels of mature bile acids. Biochim Biophys Acta 1831(8):1335–1343. doi: 10.1016/j.bbalip.2013.05.002 PubMedGoogle Scholar
  140. Setchell KD, Heubi JE, Shah S, Lavine JE, Suskind D, Al-Edreesi M, Potter C, Russell DW, O’Connell NC, Wolfe B, Jha P, Zhang W, Bove KE, Knisely AS, Hofmann AF, Rosenthal P, Bull LN (2013) Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. Gastroenterology 144(5):945–955 e946; quiz e914–945. doi: 10.1053/j.gastro.2013.02.004
  141. Smith EH, Gavrilov DK, Oglesbee D, Freeman WD, Vavra MW, Matern D, Tortorelli S (2010) An adult onset case of alpha-methyl-acyl-CoA racemase deficiency. J Inherit Metab Dis 33(Suppl 3):S349–S353. doi: 10.1007/s10545-010-9183-6 PubMedGoogle Scholar
  142. Suzuki Y, Jiang LL, Souri M, Miyazawa S, Fukuda S, Zhang Z, Une M, Shimozawa N, Kondo N, Orii T, Hashimoto T (1997) D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder. Am J Hum Genet 61(5):1153–1162. doi: 10.1086/301599 PubMedCentralPubMedGoogle Scholar
  143. Sztriha L, Al-Gazali LI, Wanders RJ, Ofman R, Nork M, Lestringant GG (2000) Abnormal myelin formation in rhizomelic chondrodysplasia punctata type 2 (DHAPAT-deficiency). Dev Med Child Neurol 42(7):492–495PubMedGoogle Scholar
  144. Takahara S (1952) Progressive oral gangrene probably due to lack of catalase in the blood (acatalasaemia); report of nine cases. Lancet 2(6745):1101–1104PubMedGoogle Scholar
  145. Teigler A, Komljenovic D, Draguhn A, Gorgas K, Just WW (2009) Defects in myelination, paranode organization and Purkinje cell innervation in the ether lipid-deficient mouse cerebellum. Hum Mol Genet 18(11):1897–1908. doi: 10.1093/hmg/ddp110 PubMedCentralPubMedGoogle Scholar
  146. ten Brink HJ, Wanders RJ, Stellaard F, Schutgens RB, Jakobs C (1991) Pristanic acid and phytanic acid in plasma from patients with a single peroxisomal enzyme deficiency. J Inherit Metab Dis 14(3):345–348PubMedGoogle Scholar
  147. Thompson SA, Calvin J, Hogg S, Ferdinandusse S, Wanders RJ, Barker RA (2009) Relapsing encephalopathy in a patient with alpha-methylacyl-CoA racemase deficiency. BMJ Case Rep 2009. doi: 10.1136/bcr.08.2008.0814
  148. Une M, Konishi M, Suzuki Y, Akaboshi S, Yoshii M, Kuramoto T, Fujimura K (1997) Bile acid profiles in a peroxisomal D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency. J Biochem 122(3):655–658PubMedGoogle Scholar
  149. van den Bosch H, de Vet EC (1997) Alkyl-dihydroxyacetonephosphate synthase. Biochim Biophys Acta 1348(1–2):35–44PubMedGoogle Scholar
  150. van den Brink DM, Wanders RJ (2006) Phytanic acid: production from phytol, its breakdown and role in human disease. Cell Mol Life Sci 63(15):1752–1765. doi: 10.1007/s00018-005-5463-y PubMedGoogle Scholar
  151. van Geel BM, Bezman L, Loes DJ, Moser HW, Raymond GV (2001) Evolution of phenotypes in adult male patients with X-linked adrenoleukodystrophy. Ann Neurol 49(2):186–194PubMedGoogle Scholar
  152. van Roermund CW, Visser WF, Ijlst L, Waterham HR, Wanders RJ (2011) Differential substrate specificities of human ABCD1 and ABCD2 in peroxisomal fatty acid beta-oxidation. Biochim Biophys Acta 1811(3):148–152. doi: 10.1016/j.bbalip.2010.11.010 PubMedGoogle Scholar
  153. Van Veldhoven PP (2010) Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism. J Lipid Res 51(10):2863–2895. doi: 10.1194/jlr.R005959 PubMedCentralPubMedGoogle Scholar
  154. Verheijden S, Bottelbergs A, Krysko O, Krysko DV, Beckers L, De Munter S, Van Veldhoven PP, Wyns S, Kulik W, Nave KA, Ramer MS, Carmeliet P, Kassmann CM, Baes M (2013) Peroxisomal multifunctional protein-2 deficiency causes neuroinflammation and degeneration of Purkinje cells independent of very long chain fatty acid accumulation. Neurobiol Dis 58C:258–269. doi: 10.1016/j.nbd.2013.06.006 Google Scholar
  155. Verhoeven NM, Jakobs C, Carney G, Somers MP, Wanders RJ, Rizzo WB (1998a) Involvement of microsomal fatty aldehyde dehydrogenase in the alpha-oxidation of phytanic acid. FEBS Lett 429(3):225–228PubMedGoogle Scholar
  156. Verhoeven NM, Wanders RJ, Poll-The BT, Saudubray JM, Jakobs C (1998b) The metabolism of phytanic acid and pristanic acid in man: a review. J Inherit Metab Dis 21(7):697–728PubMedGoogle Scholar
  157. Wanders RJ, Waterham HR (2006a) Biochemistry of mammalian peroxisomes revisited. Annu Rev Biochem 75:295–332. doi: 10.1146/annurev.biochem.74.082803.133329 PubMedGoogle Scholar
  158. Wanders RJ, Waterham HR (2006b) Peroxisomal disorders: the single peroxisomal enzyme deficiencies. Biochim Biophys Acta 1763(12):1707–1720. doi: 10.1016/j.bbamcr.2006.08.010 PubMedGoogle Scholar
  159. Wanders RJ, Romeyn GJ, van Roermund CW, Schutgens RB, van den Bosch H, Tager JM (1988) Identification of L-pipecolate oxidase in human liver and its deficiency in the Zellweger syndrome. Biochem Biophys Res Commun 154(1):33–38PubMedGoogle Scholar
  160. Wanders RJ, Denis S, van Berkel E, Wouters F, Wirtz KW, Seedorf U (1998) Identification of the newly discovered 58 kDa peroxisomal thiolase SCPx as the main thiolase involved in both pristanic acid and trihydroxycholestanoic acid oxidation: implications for peroxisomal beta-oxidation disorders. J Inherit Metab Dis 21(3):302–305PubMedGoogle Scholar
  161. Wanders RJ, Komen J, Ferdinandusse S (2011) Phytanic acid metabolism in health and disease. Biochim Biophys Acta 1811(9):498–507. doi: 10.1016/j.bbalip.2011.06.006 PubMedGoogle Scholar
  162. Waterham HR, Ebberink MS (2012) Genetics and molecular basis of human peroxisome biogenesis disorders. Biochim Biophys Acta 1822(9):1430–1441. doi: 10.1016/j.bbadis.2012.04.006 PubMedGoogle Scholar
  163. Weinhofer I, Forss-Petter S, Kunze M, Zigman M, Berger J (2005) X-linked adrenoleukodystrophy mice demonstrate abnormalities in cholesterol metabolism. FEBS Lett 579(25):5512–5516. doi: 10.1016/j.febslet.2005.09.014 PubMedGoogle Scholar
  164. Westin MA, Hunt MC, Alexson SE (2005) The identification of a succinyl-CoA thioesterase suggests a novel pathway for succinate production in peroxisomes. J Biol Chem 280(46):38125–38132. doi: 10.1074/jbc.M508479200 PubMedGoogle Scholar
  165. Westin MA, Hunt MC, Alexson SE (2008) Short- and medium-chain carnitine acyltransferases and acyl-CoA thioesterases in mouse provide complementary systems for transport of beta-oxidation products out of peroxisomes. Cell Mol Life Sci 65(6):982–990. doi: 10.1007/s00018-008-7576-6 PubMedGoogle Scholar
  166. Weylandt KH, Chiu CY, Gomolka B, Waechter SF, Wiedenmann B (2012) Omega-3 fatty acids and their lipid mediators: towards an understanding of resolvin and protectin formation. Prostaglandins Other Lipid Mediat 97(3–4):73–82. doi: 10.1016/j.prostaglandins.2012.01.005 PubMedGoogle Scholar
  167. White AL, Modaff P, Holland-Morris F, Pauli RM (2003) Natural history of rhizomelic chondrodysplasia punctata. Am J Med Genet A 118A(4):332–342. doi: 10.1002/ajmg.a.20009 PubMedGoogle Scholar
  168. Wierzbicki AS, Lloyd MD, Schofield CJ, Feher MD, Gibberd FB (2002) Refsum’s disease: a peroxisomal disorder affecting phytanic acid alpha-oxidation. J Neurochem 80(5):727–735PubMedGoogle Scholar
  169. Wiese S, Gronemeyer T, Ofman R, Kunze M, Grou CP, Almeida JA, Eisenacher M, Stephan C, Hayen H, Schollenberger L, Korosec T, Waterham HR, Schliebs W, Erdmann R, Berger J, Meyer HE, Just W, Azevedo JE, Wanders RJ, Warscheid B (2007) Proteomics characterization of mouse kidney peroxisomes by tandem mass spectrometry and protein correlation profiling. Mol Cell Proteomics 6(12):2045–2057. doi: 10.1074/mcp.M700169-MCP200 PubMedGoogle Scholar
  170. Wiesinger C, Kunze M, Regelsberger G, Forss-Petter S, Berger J (2013) Impaired very long-chain acyl-CoA beta-oxidation in human X-linked adrenoleukodystrophy fibroblasts is a direct consequence of ABCD1 transporter dysfunction. J Biol Chem 288(26):19269–19279. doi: 10.1074/jbc.M112.445445 PubMedCentralPubMedGoogle Scholar
  171. Willemsen MA, IJlst L, Steijlen PM, Rotteveel JJ, de Jong JG, van Domburg PH, Mayatepek E, Gabreels FJ, Wanders RJ (2001) Clinical, biochemical and molecular genetic characteristics of 19 patients with the Sjogren-Larsson syndrome. Brain 124(Pt 7):1426–1437PubMedGoogle Scholar

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© Springer-Verlag Wien 2014

Authors and Affiliations

  1. 1.Department of Pathobiology of the Nervous System, Center for Brain ResearchMedical University of ViennaViennaAustria

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