苯丙氨酸羥化酶
| 苯丙氨酸羥化酶 | |||||||||||||
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 苯丙氨酸羥化酶的三維結構預測 | |||||||||||||
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| 標識 | |||||||||||||
| 代號 | PAH; PH; PKU; PKU1 | ||||||||||||
| 擴展標識 | 遺傳學：612349 鼠基因：97473 同源基因：234 ChEMBL: 3076 GeneCards: PAH Gene | ||||||||||||
| EC編號 | 1.14.16.1 | ||||||||||||
| RNA表達模式 | |||||||||||||
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| 更多表達數據 | |||||||||||||
| 直系同源體 | |||||||||||||
| 物種 | 人類 | 小鼠 | |||||||||||
| Entrez | 5053 | 18478 | |||||||||||
| Ensembl | ENSG00000171759 | ENSMUSG00000020051 | |||||||||||
| UniProt | P00439 | P16331 | |||||||||||
| mRNA序列 | NM_000277 | NM_008777 | |||||||||||
| 蛋白序列 | NP_000268 | NP_032803 | |||||||||||
| 基因位置 |
Chr 12: 103.23 – 103.35 Mb |
Chr 10: 87.52 – 87.58 Mb | |||||||||||
| PubMed查詢 | [1] | [2] | |||||||||||
苯丙氨酸羥化酶 (英語：Phenylalanine hydroxylase，簡稱PheOH,或者PheH、PAH) (EC 1.14.16.1) 是一種將苯丙氨酸側鏈上的苯環羥基化為酪氨酸的羥化酶。 PheOH是使用四氫生物蝶呤(BH4,蝶啶類輔因子)和亞鐵離子(Fe2+)作為輔酶的單加氧酶類蛋白質三種中的一種。在反應中，一個氧分子的兩個氧原子被分別加入到BH4和苯丙氨酸中。[1]
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苯丙氨酸羥化酶是體內過量苯丙氨酸分解代謝的限速酶。Seymour Kaufman關於苯丙氨酸羥化酶的研究使一種新的生物輔酶四氫生物蝶呤被發現。[2] 此酶受到人類健康方面的關注是因為編碼該酶的PAH基因如果發生突變，會造成嚴重的代謝紊亂即苯丙酮尿症
酶反應機制
反應認為是按照以下步驟進行：
- 形成 Fe(II)-O-O-BH4 橋.
- O-O鍵異裂產生鐵氧羥化中間體 Fe(IV)=O.
- attack on Fe(IV)=O to hydroxylate phenylalanine substrate to tyrosine.[3]
酶調控
結構
51.9千道爾頓的PheOH蛋白質分子單體可以分為三個結構域: N端結構域 (氨基酸殘基1-117), 催化結構域 (殘基118-427), 以及負責相同單體聚合的C端結構域 (殘基428-453) 。
生物學功能
PheOH是苯丙氨酸完全分解代謝為二氧化碳和水這一過程的關鍵酶，催化限速步驟。[5]
有關酶
苯丙氨酸羥化酶與以下兩種酶密切相關：
這三種酶是同源的，由共同的祖先古羥化酶進化而來。
參考文獻
- ^ Fitzpatrick PF. Tetrahydropterin-dependent amino acid hydroxylases. Annu. Rev. Biochem. 1999, 68: 355–81. PMID 10872454. doi:10.1146/annurev.biochem.68.1.355.
- ^ KAUFMAN S. A new cofactor required for the enzymatic conversion of phenylalanine to tyrosine. J. Biol. Chem. February 1958, 230 (2): 931–9. PMID 13525410.
- ^ Fitzpatrick PF. Mechanism of aromatic amino acid hydroxylation. Biochemistry. December 2003, 42 (48): 14083–91. PMC 1635487
. PMID 14640675. doi:10.1021/bi035656u.
- ^ T. Selwood and E. K. Jaffe. Dynamic dissociating homo-oligomers and the control of protein function.. Arch. Biochem. Biophys. 2011, 519 (2): 131–43 [2013-04-28]. PMC 3298769 . PMID 22182754. doi:10.1016/j.abb.2011.11.020. （原始內容存檔於2007-05-12）.
- ^ Kaufman S. A model of human phenylalanine metabolism in normal subjects and in phenylketonuric patients. Proc. Natl. Acad. Sci. U.S.A. March 1999, 96 (6): 3160–4. PMC 15912 . PMID 10077654. doi:10.1073/pnas.96.6.3160.
擴展閱讀
- Eisensmith RC, Woo SL. Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene.. Hum. Mutat. 1993, 1 (1): 13–23. PMID 1301187. doi:10.1002/humu.1380010104.
- Konecki DS, Lichter-Konecki U. The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations.. Hum. Genet. 1991, 87 (4): 377–88. PMID 1679029. doi:10.1007/BF00197152.
- Cotton RG. Heterogeneity of phenylketonuria at the clinical, protein and DNA levels.. J. Inherit. Metab. Dis. 1991, 13 (5): 739–50. PMID 2246858. doi:10.1007/BF01799577.
- Erlandsen H, Fusetti F, Martinez A; et al. Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria.. Nat. Struct. Biol. 1998, 4 (12): 995–1000. PMID 9406548. doi:10.1038/nsb1297-995.
- Waters PJ, Parniak MA, Nowacki P, Scriver CR. In vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to function.. Hum. Mutat. 1998, 11 (1): 4–17. PMID 9450897. doi:10.1002/(SICI)1098-1004(1998)11:13.0.CO;2-L.
- Waters PJ. How PAH gene mutations cause hyper-phenylalaninemia and why mechanism matters: insights from in vitro expression.. Hum. Mutat. 2003, 21 (4): 357–69. PMID 12655545. doi:10.1002/humu.10197.