Peroxisomes biogenesis

Gould SJ et al The peroxisome biogenesis disorders. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR et al (editors). McGraw-Hill, 2001. 

Disorders of peroxisome biogenesis 689 Defects of single peroxisomal enzymes 691... 

Barth, P. G., Majoie, C. B., Gootjes, J. et al. Neuroimaging of peroxisome biogenesis disorders (Zellweger spectrum) with prolonged survival. Neurology 62 439-444, 2004. 

PBD peroxisome biogenesis disorders PTEN phosphatase and tensin homolog... 

Kunau, W. (1998). Peroxisome biogenesis from yeast to man. Curr. Opin. Microbiol. 1, 232-237. 

Olsen, L. (1998). The surprising complexity of peroxisome biogenesis. Plant Mol. Biol. 38, 163-189. 

UBCIO 165 [75] Unknown Also called Pas2/Pexl0. Peroxisome biogenesis [75] PexlO is a candidate E3 [78]... 

UbclO is required for the biogenesis of the peroxisome, an oxidative organelle [75]. This E2 plays a role in peroxisomal protein import [76] and is recruited to the peroxisomal membrane through an interaction with a partner protein [77]. Membrane-localized UbclO also seems to be spatially proximal to PexlO, which has a RING-like domain [78]. Whether PexlO is a cognate E3 of UbclO remains to be determined, as does the mechanistic role of ubiquitin conjugation in peroxisome biogenesis. 

WiEBEL, F. F. and Kunau, W. H. The Pas2 protein essential for peroxisome biogenesis is related to ubiquitin-conjugating enzymes. Nature 1992,... 

The analysis of cells lacking a specific E2 demonstrated that they are involved in a large variety of cellular processes, like cell cycle control, DNA repair, peroxisome biogenesis, stress response and resistance to heavy metals. However, the analysis of specific proteolytic substrates revealed that Ubc s seemed to be redundant in function. Furthermore, ubiquitin-con-jugating enzymes may function in dimeric complexes with ofiier Ubc s, which may alter the substrate specificity of the involved enzymes (Chen et al. 1993). The current knowledge on the yeast Ubc s is summarized in Table 1. 

Zellweger syndrome Is a llpid storage disorder caused by impaired peroxisome biogenesis due to deficiency or functional defect of one of eleven proteins involved in the complex mechanism of peroxisomal matrix protein import and assembly of the organelle. 

The presence of PA in patients with defective peroxisomal metabohsm may be a diagnostic tool in distinguishing the peroxisome biogenesis defects from isolated enzyme... 

Patients with a peroxisome biogenesis defect (Zellweger syndrome) are especially low in DHA for two reasons (1) they have no peroxisomal fatty acid /1-oxidation and... 

In contrast to the general peroxisome biogenesis defects, patients with X-linked adrenoleucodystrophy, whose very-long-chain fatty acid oxidation is impaired as a result of an uptake defect, show minimal abnormalities of their DHA levels. 

Phytanic and pristanic acid results should always be interpreted in conjunction with each other. In general, patients with a peroxisome biogenesis defect or a de-... 

Unfortunately, a minority of the patients with peroxisomal dysfunction cannot be diagnosed using plasma parameters. In the authors laboratory, patients have been seen with peroxisome biogenesis defects, D-bifunctional protein deficiency, and acyl-CoA oxidase deficiency in whom no abnormalities of plasma VLCFA, phytanic acid, pristanic acid or bile acids could be established. Hence, a strong clinical suspicion of peroxisomal disease should always be verified by fibroblast investigation, regardless of the outcome of plasma analyses. 

Rizzo C, Boenzi S, Wanders RJA, 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-MS. Pediatr Res 53 1-6... 

Peroxisomal disorders (Zellweger syndrome, Refsum s disease, neonatal adre-noleukodystrophy) are characterised by defective peroxisome biogenesis, or, being present, peroxisomes lacking / -oxidative enzymes. In the BA biosynthetic pathway, dihydroxycoprostanic acid (DHCA) and trihydroxycoprostanic acid (THCA) are /1-oxidised in peroxisomes to produce CA and CDCA, respectively, whereas peroxisomal disorders cause a defective oxidation of the BA precursor side chain, which leads to an accumulation of C27 bile acids, notably 3 ,7 -dihydroxy-5/3-cholesta-noic acid (DHCA) and 3a,7a,12a-trihydroxy-5/l-cholestanoic acid (THCA), in the plasma and urine of affected patients. 

Fujiki, Y (2000). Peroxisome biogenesis and peroxisome biogenesis disorders. FEBSLett. 476, 42-46. 

Martinez, M. (1996) Docosahexaenoic acid therapy in docosahexaenoic acid-deficient patients with disorders of peroxisomal biogenesis. Lipids. 31 S145-S152. 

R. Frdmann, F.F. Wiebel, A. Flessau, J. Rytka, a. Beyer, K. U. Frohlich, and W. H. Kunau, PASl, a yeast gene required for peroxisome biogenesis, encodes a member of a novel family of putative ATPases, Cell, 1991, 64, 499-510. 

Docosahexaenoic Acid Therapy for Disorders of Peroxisome Biogenesis... 

The rationale for DHA therapy in the disorders of peroxisome biogenesis is compelling at first glance DHA is essential for nonnal function of brain and retina PBD patients cannot synthesize DHA and, thus, have adeficicncy of this substance oral administration of DHA can normalize levels of DHA in plasma and red cells and probably also in brain and retina DHA therapy is simple and not excessively expensive and it appears to be free of significant side effects. Finally, the nonrandomized studies that have been published... 

Gartner J, Preuss N. Brosius U. Biermanns M. Mutations in PEXl in peroxisome biogenesis disorders G843D and a mild clinical phenotype. J Inherited Metab Dis 1999 22(3) 311-313. 

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