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Pathway Description
Familial Hypercholanemia (FHCA)
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-09-15
Familial Hypercholanemia can be caused by mutations in the TJP2, BAAT or EPHX1 genes which code for bile acid-CoA:amino acid N-acyltransferase, which plays a part in the metabolism of in bile acids. This enzyme plays a particularly important role in the hepatocytes of the liver. In this region the said enzyme is in part responsible for the catalysis of C24 bile acids (also known as choloneates) at a point preceding excretion into bile canaliculi. Bile is made up of many components, though two major ones are chenodeoxycholic acid and cholic acid. First, the bile acids undergo a process of conversion into acyl-CoA thioester. This occurs in two regions: in peroxisomes or endoplasmic reticulum (the latter are known as the secondary bile acids). Second, the bile acids undergo a process of conjugation which increases the detergent property, in particular in the intestine. In turn, the absorption of vitamins which are lipid soluble is faciliatated. In later steps, the deconjugation of bile acids is performed by bacteria and at this stage the bile acids are then returned to the liver to once again undergo the process of reconjugation. Familial hypercholanemia is characterized by increased bile acids in plasma. Symptoms include rickets and steatorrhea.
References
Familial Hypercholanemia (FHCA) References
Carlton VE, Harris BZ, Puffenberger EG, Batta AK, Knisely AS, Robinson DL, Strauss KA, Shneider BL, Lim WA, Salen G, Morton DH, Bull LN: Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. Nat Genet. 2003 May;34(1):91-6. doi: 10.1038/ng1147.
Pubmed: 12704386
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 SMP0000317
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