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Pathway Description
Homocystinuria, Cystathionine beta-Synthase Deficiency
Homo sapiens
Disease Pathway
Created: 2022-12-20
Last Updated: 2023-10-25
Homocystinuria, Cystathionine beta-Synthase Deficiency, also known as homocystinuria, is a inherited disorder of amino acid methionine metabolism caused by a defective cystathionine beta-Synthase. Cystathionine beta-Synthase catalyzes the conversion of homocysteine and L-Serine into L-Cystathionine which is the substrate of cystathionine gamma-lyase. This disorder is characterized by a large accumulation of homocysteine in the cell. Symptoms of the disorder include thromboembolism, ectopia lentis and/or severe myopia, skeletal system deficiency and developmental delay. Treatment with homocystinuria aims at correct the biochemical abnormalities through disorder management (e.g. surveillance, circumstances to avoid, prevention of primary manifestations, etc.
References
Homocystinuria, Cystathionine beta-Synthase Deficiency References
https://en.wikipedia.org/wiki/Homocystinuria
Sacharow SJ, Picker JD, Levy HL: Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency.
Pubmed: 20301697
Finkelstein JD: Methionine metabolism in mammals. J Nutr Biochem. 1990 May;1(5):228-37. doi: 10.1016/0955-2863(90)90070-2.
Pubmed: 15539209
Griffith OW: Mammalian sulfur amino acid metabolism: an overview. Methods Enzymol. 1987;143:366-76. doi: 10.1016/0076-6879(87)43065-6.
Pubmed: 3309559
Stipanuk MH: Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. Annu Rev Nutr. 2004;24:539-77. doi: 10.1146/annurev.nutr.24.012003.132418.
Pubmed: 15189131
Kraus JP, Oliveriusova J, Sokolova J, Kraus E, Vlcek C, de Franchis R, Maclean KN, Bao L, Bukovsk, Patterson D, Paces V, Ansorge W, Kozich V: The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms. Genomics. 1998 Sep 15;52(3):312-24.
Pubmed: 9790750
Kraus JP, Janosik M, Kozich V, Mandell R, Shih V, Sperandeo MP, Sebastio G, de Franchis R, Andria G, Kluijtmans LA, Blom H, Boers GH, Gordon RB, Kamoun P, Tsai MY, Kruger WD, Koch HG, Ohura T, Gaustadnes M: Cystathionine beta-synthase mutations in homocystinuria. Hum Mutat. 1999;13(5):362-75. doi: 10.1002/(SICI)1098-1004(1999)13:5<362::AID-HUMU4>3.0.CO;2-K.
Pubmed: 10338090
Kraus JP, Le K, Swaroop M, Ohura T, Tahara T, Rosenberg LE, Roper MD, Kozich V: Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells. Hum Mol Genet. 1993 Oct;2(10):1633-8. doi: 10.1093/hmg/2.10.1633.
Pubmed: 7903580
Wang J, Hegele RA: Genomic basis of cystathioninuria (MIM 219500) revealed by multiple mutations in cystathionine gamma-lyase (CTH). Hum Genet. 2003 Apr;112(4):404-8. doi: 10.1007/s00439-003-0906-8. Epub 2003 Feb 6.
Pubmed: 12574942
Lu Y, O'Dowd BF, Orrego H, Israel Y: Cloning and nucleotide sequence of human liver cDNA encoding for cystathionine gamma-lyase. Biochem Biophys Res Commun. 1992 Dec 15;189(2):749-58. doi: 10.1016/0006-291x(92)92265-y.
Pubmed: 1339280
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Pineda M, Fernandez E, Torrents D, Estevez R, Lopez C, Camps M, Lloberas J, Zorzano A, Palacin M: Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids. J Biol Chem. 1999 Jul 9;274(28):19738-44. doi: 10.1074/jbc.274.28.19738.
Pubmed: 10391915
Rossier G, Meier C, Bauch C, Summa V, Sordat B, Verrey F, Kuhn LC: LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine. J Biol Chem. 1999 Dec 3;274(49):34948-54. doi: 10.1074/jbc.274.49.34948.
Pubmed: 10574970
Borsani G, Bassi MT, Sperandeo MP, De Grandi A, Buoninconti A, Riboni M, Manzoni M, Incerti B, Pepe A, Andria G, Ballabio A, Sebastio G: SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. Nat Genet. 1999 Mar;21(3):297-301. doi: 10.1038/6815.
Pubmed: 10080183
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