苯丙氨酸羟化酶

苯丙氨酸羟化酶
苯丙氨酸羟化酶
	苯丙氨酸羟化酶的三维结构预测
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	1DMW, 1J8T, 1J8U, 1KW0, 1LRM, 1MMK, 1MMT, 1PAH, 1TDW, 1TG2, 2PAH, 3PAH, 4ANP, 4PAH, 5PAH, 6PAH
标识
代号	PAH; PH; PKU; PKU1
扩展标识	遗传学：612349 鼠基因：97473 同源基因：234 ChEMBL: 3076 GeneCards: PAH Gene
EC編號	1.14.16.1
基因本体论描述
分子功能	· phenylalanine 4-monooxygenase activity; · iron ion binding; · amino acid binding;
细胞成分	· cytosol;
生物过程	· L-phenylalanine catabolic process; · cellular amino acid biosynthetic process; · cellular nitrogen compound metabolic process; · neurotransmitter biosynthetic process; · catecholamine biosynthetic process; · small molecule metabolic process;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体
物种	人类
Entrez	5053
Ensembl	ENSG00000171759
UniProt	P00439
mRNA序列	NM_000277
蛋白序列	NP_000268
基因位置	Chr 12:; 103.23 – 103.35 Mb
PubMed查询	[1]
	查; 论; 编;

苯丙氨酸羟化酶 (英語：Phenylalanine hydroxylase，简称PheOH,或者PheH、PAH) (EC 1.14.16.1) 是一种将苯丙氨酸侧链上的苯环羟基化为酪氨酸的羟化酶。 PheOH是使用四氢生物蝶呤(BH₄,蝶啶类辅因子)和亚铁离子(Fe²⁺)作为辅酶的单加氧酶类蛋白质三种中的一种。在反应中，一个氧分子的两个氧原子被分别加入到BH₄和苯丙氨酸中。^[1]

Reaction catalyzed by PheOH. — PheOH催化的反应

苯丙氨酸羟化酶是体内过量苯丙氨酸分解代谢的限速酶。Seymour Kaufman关于苯丙氨酸羟化酶的研究使一种新的生物辅酶四氢生物蝶呤被发现。^[2] 此酶受到人类健康方面的关注是因为编码该酶的PAH基因如果发生突变，会造成严重的代谢紊乱即苯丙酮尿症

酶反应机制

反应认为是按照以下步骤进行：

形成 Fe(II)-O-O-BH₄ 桥.
O-O键异裂产生铁氧羟化中间体 Fe(IV)=O.
attack on Fe(IV)=O to hydroxylate phenylalanine substrate to tyrosine.^[3]

Formation and cleavage of a Fe(II)-O-O-BH4 bridge.. — PheOH mechanism, part I

酶调控

该酶可能以morpheein模式进行别构调节。^[4]

结构

苯丙氨酸羟化酶的化学式为：C₂₃₅₀H₃₆₂₅O₆₈₃N₆₁₉S₁₂（注：磷酸化苯丙氨酸羟化酶分子式为：C₂₃₅₀H₃₆₂₆O₆₈₆N₆₁₉S₁₂P ，Ser-16 位點的磷酸化增加了基礎活性並促進了底物苯丙氨酸的啟動。）^[5]，分子量为：51.9千道尔顿的PheOH蛋白质分子单体可以分为三个结构域: N端结构域 (氨基酸残基1-117), 催化结构域 (残基118-427), 以及负责相同单体聚合的C端结构域 (残基428-453) 。

生物学功能

PheOH是苯丙氨酸完全分解代谢为二氧化碳和水这一过程的关键酶，催化限速步骤。^[6]

有关酶

苯丙氨酸羟化酶与以下两种酶密切相关：

色氨酸羟化酶 (EC编号 1.14.16.4)，调控大脑与消化系统中的血清素水平。
酪氨酸羟化酶 (EC编号 1.14.16.2), 调控大脑与肾上腺髓质中的多巴胺、肾上腺素与去甲肾上腺素水平。

这三种酶是同源的，由共同的祖先古羟化酶进化而来。

参考文献

^ 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. （原始内容存档于2007-05-12）.
^ UniProt. UniProt. [2025-05-14] （英语）.
^ 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.

扩展阅读

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.

外部链接

[Fitzpatrick1999-1] Fitzpatrick PF. Tetrahydropterin-dependent amino acid hydroxylases. Annu. Rev. Biochem. 1999, 68: 355–81. PMID 10872454. doi:10.1146/annurev.biochem.68.1.355.

[pmid13525410-2] 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_2003-3] Fitzpatrick PF. Mechanism of aromatic amino acid hydroxylation. Biochemistry. December 2003, 42 (48): 14083–91. PMC 1635487 . PMID 14640675. doi:10.1021/bi035656u.

[pmid22182754-4] 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. （原始内容存档于2007-05-12）.

[5] UniProt. UniProt. [2025-05-14] （英语）.

[Kaufman_1999-6] 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.

[1]

[2]

[3]

[4]

[5]

[6]