Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Zellweger Syndrome
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-08-16
Zellweger syndrome, also known as cerebrohepatorenal syndrome, is an autosomal recessive peroxisome biogenesis disorder that is part of the family of Zellweger spectrum disorders. It is caused by a defect in one of 12 or more of the PEX genes (PEX1, 2, 3, 5, 6, 10, 12, 13, 14, 16, 19 and 26) that produce proteins called peroxins. Peroxins are used in the formation of peroxisomes, and can be involved in recognition of proteins targeted for the peroxisome, as well as their transport into the peroxisome. Peroxisomes typically break down both very long chain and branched fatty acids, but if they aren't present, these fatty acids build up in the blood and body, harming organs such as the brain and liver. Additionally, due to the fact that some processes, such as plasmalogen biosynthesis, occur in or using peroxisomes, and can lead to deficiencies in plasmalogens. These are important in brain and lung function, leading to other symptoms.
Zellweger syndrome is characterized by an increase in levels of very long chain fatty acids in the blood plasma, as well as more visible physical symptoms, such as an abnormally large or small head at birth, characteristic facial features and poor muscle tone, which can lead to an inability of infants to feed. Other symptoms include an enlarged liver, skeletal abnormalities and low CNS function. Infants very rarely live longer than one year, and the only treatment is for symptoms the patient is experiencing, not for the syndrome itself.
References
Zellweger Syndrome References
Schutgens RB, Wanders RJ, Heymans HS, Schram AW, Tager JM, Schrakamp G, van den Bosch H: Zellweger syndrome: biochemical procedures in diagnosis, prevention and treatment. J Inherit Metab Dis. 1987;10 Suppl 1:33-45.
Pubmed: 3119940
Bile Acid Biosynthesis References
Pawlowski JE, Huizinga M, Penning TM: Cloning and sequencing of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. J Biol Chem. 1991 May 15;266(14):8820-5.
Pubmed: 1840601
Stolz A, Rahimi-Kiani M, Ameis D, Chan E, Ronk M, Shively JE: Molecular structure of rat hepatic 3 alpha-hydroxysteroid dehydrogenase. A member of the oxidoreductase gene family. J Biol Chem. 1991 Aug 15;266(23):15253-7.
Pubmed: 1714456
Cheng KC, White PC, Qin KN: Molecular cloning and expression of rat liver 3 alpha-hydroxysteroid dehydrogenase. Mol Endocrinol. 1991 Jun;5(6):823-8. doi: 10.1210/mend-5-6-823.
Pubmed: 1922097
Onishi Y, Noshiro M, Shimosato T, Okuda K: Molecular cloning and sequence analysis of cDNA encoding delta 4-3-ketosteroid 5 beta-reductase of rat liver. FEBS Lett. 1991 Jun 3;283(2):215-8. doi: 10.1016/0014-5793(91)80591-p.
Pubmed: 1710579
Onishi Y, Noshiro M, Shimosato T, Okuda K: delta 4-3-Oxosteroid 5 beta-reductase. Structure and function. Biol Chem Hoppe Seyler. 1991 Dec;372(12):1039-49.
Pubmed: 1789929
Zhu Y, Fillenwarth MJ, Crabb D, Lumeng L, Lin RC: Identification of the 37-kd rat liver protein that forms an acetaldehyde adduct in vivo as delta 4-3-ketosteroid 5 beta-reductase. Hepatology. 1996 Jan;23(1):115-22. doi: 10.1002/hep.510230116.
Pubmed: 8550030
Usui E, Noshiro M, Okuda K: Molecular cloning of cDNA for vitamin D3 25-hydroxylase from rat liver mitochondria. FEBS Lett. 1990 Mar 12;262(1):135-8. doi: 10.1016/0014-5793(90)80172-f.
Pubmed: 2318307
Su P, Rennert H, Shayiq RM, Yamamoto R, Zheng YM, Addya S, Strauss JF 3rd, Avadhani NG: A cDNA encoding a rat mitochondrial cytochrome P450 catalyzing both the 26-hydroxylation of cholesterol and 25-hydroxylation of vitamin D3: gonadotropic regulation of the cognate mRNA in ovaries. DNA Cell Biol. 1990 Nov;9(9):657-67. doi: 10.1089/dna.1990.9.657.
Pubmed: 2175615
Shayiq RM, Avadhani NG: Sequence complementarity between the 5'-terminal regions of mRNAs for rat mitochondrial cytochrome P-450c27/25 and a growth hormone-inducible serine protease inhibitor. A possible gene overlap. J Biol Chem. 1992 Feb 5;267(4):2421-8.
Pubmed: 1733943
Falany CN, Xie X, Wheeler JB, Wang J, Smith M, He D, Barnes S: Molecular cloning and expression of rat liver bile acid CoA ligase. J Lipid Res. 2002 Dec;43(12):2062-71. doi: 10.1194/jlr.m200260-jlr200.
Pubmed: 12454267
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Reichel C, Brugger R, Bang H, Geisslinger G, Brune K: Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen. Mol Pharmacol. 1997 Apr;51(4):576-82. doi: 10.1124/mol.51.4.576.
Pubmed: 9106621
Schmitz W, Helander HM, Hiltunen JK, Conzelmann E: Molecular cloning of cDNA species for rat and mouse liver alpha-methylacyl-CoA racemases. Biochem J. 1997 Sep 15;326 ( Pt 3):883-9. doi: 10.1042/bj3260883.
Pubmed: 9307041
Kotti TJ, Savolainen K, Helander HM, Yagi A, Novikov DK, Kalkkinen N, Conzelmann E, Hiltunen JK, Schmitz W: In mouse alpha -methylacyl-CoA racemase, the same gene product is simultaneously located in mitochondria and peroxisomes. J Biol Chem. 2000 Jul 7;275(27):20887-95. doi: 10.1074/jbc.M002067200.
Pubmed: 10770938
Baumgart E, Vanhooren JC, Fransen M, Van Leuven F, Fahimi HD, Van Veldhoven PP, Mannaerts GP: Molecular cloning and further characterization of rat peroxisomal trihydroxycoprostanoyl-CoA oxidase. Biochem J. 1996 Nov 15;320 ( Pt 1):115-21. doi: 10.1042/bj3200115.
Pubmed: 8947475
Van Veldhoven PP, Vanhove G, Assselberghs S, Eyssen HJ, Mannaerts GP: Substrate specificities of rat liver peroxisomal acyl-CoA oxidases: palmitoyl-CoA oxidase (inducible acyl-CoA oxidase), pristanoyl-CoA oxidase (non-inducible acyl-CoA oxidase), and trihydroxycoprostanoyl-CoA oxidase. J Biol Chem. 1992 Oct 5;267(28):20065-74.
Pubmed: 1400324
Moser K, White FM: Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS. J Proteome Res. 2006 Jan;5(1):98-104. doi: 10.1021/pr0503073.
Pubmed: 16396499
Dieuaide-Noubhani M, Novikov D, Baumgart E, Vanhooren JC, Fransen M, Goethals M, Vandekerckhove J, Van Veldhoven PP, Mannaerts GP: Further characterization of the peroxisomal 3-hydroxyacyl-CoA dehydrogenases from rat liver. Relationship between the different dehydrogenases and evidence that fatty acids and the C27 bile acids di- and tri-hydroxycoprostanic acids are metabolized by separate multifunctional proteins. Eur J Biochem. 1996 Sep 15;240(3):660-6. doi: 10.1111/j.1432-1033.1996.0660h.x.
Pubmed: 8856068
Corton JC, Bocos C, Moreno ES, Merritt A, Marsman DS, Sausen PJ, Cattley RC, Gustafsson JA: Rat 17 beta-hydroxysteroid dehydrogenase type IV is a novel peroxisome proliferator-inducible gene. Mol Pharmacol. 1996 Nov;50(5):1157-66.
Pubmed: 8913347
Qin YM, Poutanen MH, Helander HM, Kvist AP, Siivari KM, Schmitz W, Conzelmann E, Hellman U, Hiltunen JK: Peroxisomal multifunctional enzyme of beta-oxidation metabolizing D-3-hydroxyacyl-CoA esters in rat liver: molecular cloning, expression and characterization. Biochem J. 1997 Jan 1;321 ( Pt 1):21-8. doi: 10.1042/bj3210021.
Pubmed: 9003397
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000316
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings