PathBank

Pathway Description

Homocarnosinosis

Rattus norvegicus

Category:

Metabolite Pathway

Sub-Category:

Disease

Created: 2018-09-10

Last Updated: 2019-08-16

Homocarnosinosis is caused by an inherited defect in serum carnosinase, which converts homocarnosine to GABA (gamma aminobutyric acid). A defect in serum carnosinase causes accumulation of the brain specific dipeptide homocarnosine (Hca), in the CSF and brain. Symptoms include hypotonia, mental retardation, retinitis pigmentosa and spastic diplegia/quadriplegia.

References

Homocarnosinosis References

Lenney JF: Carnosinase and homocarnosinosis. J Oslo City Hosp. 1985 Feb-Mar;35(2-3):27-40.

Pubmed: 3891936

Glutamate Metabolism References

Chung-Bok MI, Vincent N, Jhala U, Watford M: Rat hepatic glutaminase: identification of the full coding sequence and characterization of a functional promoter. Biochem J. 1997 May 15;324 ( Pt 1):193-200. doi: 10.1042/bj3240193.

Pubmed: 9164856

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

Smith EM, Watford M: Molecular cloning of a cDNA for rat hepatic glutaminase. Sequence similarity to kidney-type glutaminase. J Biol Chem. 1990 Jun 25;265(18):10631-6.

Pubmed: 2191954

Huynh QK, Gulve EA, Dian T: Purification and characterization of glutamine:fructose 6-phosphate amidotransferase from rat liver. Arch Biochem Biophys. 2000 Jul 15;379(2):307-13. doi: 10.1006/abbi.2000.1895.

Pubmed: 10898949

Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.

Pubmed: 22673903

Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F: Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004 Apr 1;428(6982):493-521. doi: 10.1038/nature02426.

Pubmed: 15057822

Florea L, Di Francesco V, Miller J, Turner R, Yao A, Harris M, Walenz B, Mobarry C, Merkulov GV, Charlab R, Dew I, Deng Z, Istrail S, Li P, Sutton G: Gene and alternative splicing annotation with AIR. Genome Res. 2005 Jan;15(1):54-66. doi: 10.1101/gr.2889405.

Pubmed: 15632090

Hinderlich S, Nohring S, Weise C, Franke P, Stasche R, Reutter W: Purification and characterization of N-acetylglucosamine kinase from rat liver--comparison with UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Eur J Biochem. 1998 Feb 15;252(1):133-9. doi: 10.1046/j.1432-1327.1998.2520133.x.

Pubmed: 9523722

Nyunoya H, Broglie KE, Widgren EE, Lusty CJ: Characterization and derivation of the gene coding for mitochondrial carbamyl phosphate synthetase I of rat. J Biol Chem. 1985 Aug 5;260(16):9346-56.

Pubmed: 2991241

Lagace M, Howell BW, Burak R, Lusty CJ, Shore GC: Rat carbamyl-phosphate synthetase I gene. Promoter sequence and tissue-specific transcriptional regulation in vitro. J Biol Chem. 1987 Aug 5;262(22):10415-8.

Pubmed: 3038878

Pekkala S, Martinez AI, Barcelona B, Gallego J, Bendala E, Yefimenko I, Rubio V, Cervera J: Structural insight on the control of urea synthesis: identification of the binding site for N-acetyl-L-glutamate, the essential allosteric activator of mitochondrial carbamoyl phosphate synthetase. Biochem J. 2009 Nov 11;424(2):211-20. doi: 10.1042/BJ20090888.

Pubmed: 19754428

Iwahana H, Yamaoka T, Mizutani M, Mizusawa N, Ii S, Yoshimoto K, Itakura M: Molecular cloning of rat amidophosphoribosyltransferase. J Biol Chem. 1993 Apr 5;268(10):7225-37.

Pubmed: 8463258

Iwahana H, Honda S, Tsujisawa T, Takahashi Y, Adzuma K, Katashima R, Yamaoka T, Moritani M, Yoshimoto K, Itakura M: Rat genomic structure of amidophosphoribosyltransferase, cDNA sequence of aminoimidazole ribonucleotide carboxylase, and cell cycle-dependent expression of these two physically linked genes. Biochim Biophys Acta. 1995 Apr 26;1261(3):369-80. doi: 10.1016/0167-4781(95)00036-g.

Pubmed: 7742366

Ishiguro M, Suzuki M, Takio K, Matsuzawa T, Titani K: Complete amino acid sequence of rat liver cytosolic alanine aminotransferase. Biochemistry. 1991 Jun 18;30(24):6048-53. doi: 10.1021/bi00238a031.

Pubmed: 2043642

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 SMP0000385

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

		1-Pyrroline-5-carboxylic acid
		4Fe-4S
		5-Phosphoribosylamine
		Acetyl-CoA
		Adenosine diphosphate
		Adenosine diphosphate ribose
		Adenosine monophosphate
		Adenosine triphosphate
		Ammonia
		Biotin
		Carbamoyl phosphate
		Carbon dioxide
		Carbonic acid
		Chitin
		Coenzyme A
		FAD
		Fructose 6-phosphate
		Glucosamine 6-phosphate
		Glutathione
		Glycine
		Guanosine monophosphate
		Hydrogen Ion
		L-Alanine
		L-Aspartic acid
		L-Cysteine
		L-Glutamic acid
		L-Glutamine
		Magnesium
		N-Acetyl-D-Glucosamine 6-Phosphate
		NAD
		NADH
		NADP
		NADPH
		Nicotinic acid adenine dinucleotide
		Oxalacetic acid
		Oxidized glutathione
		Oxoglutaric acid
		Phosphate
		Phosphoribosyl pyrophosphate
		Phosphoric acid
		Pyridoxal 5'-phosphate
		Pyrophosphate
		Pyruvic acid
		Succinic acid
		Succinic acid semialdehyde
		Water
		Xanthylic acid
		Zinc (II) ion
		γ-Aminobutyric acid
		γ-Glutamylcysteine

Visualize Protein Data

		4-aminobutyrate aminotransferase, mitochondrial
		Alanine aminotransferase 1
		Amidophosphoribosyltransferase
		Aspartate aminotransferase, mitochondrial
		Carbamoyl-phosphate synthase [ammonia], mitochondrial
		Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial
		Glucosamine-phosphate N-acetyltransferase 1
		Glutamate decarboxylase 1
		Glutamate dehydrogenase 1, mitochondrial
		Glutamate--cysteine ligase catalytic subunit
		Glutamate--cysteine ligase regulatory subunit
		Glutaminase liver isoform, mitochondrial
		Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 1
		Glutamine--tRNA ligase
		Glutamine-dependent NAD(+) synthetase
		Glutamyl-tRNA synthetase 2, mitochondrial
		Glutathione reductase
		Glutathione synthetase
		GMP synthase [glutamine-hydrolyzing]
		N-acetyl-D-glucosamine kinase
		Succinate-semialdehyde dehydrogenase, mitochondrial
		Unknown

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Homocarnosinosis

Homocarnosinosis References

Glutamate Metabolism References