Biopterin defect in cofactor biosynthesis（四氢生物蝶呤缺乏） |
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由于四氢生物喋呤（BH4）是苯基丙氨酸代谢过程中的辅助物质。BH4对于许多氨基酸的生成起关键作用，如将苯丙氨酸转化为酪氨酸；BH还参与一些神经递质的合成，如多巴胺和血清素，从而影响大脑对人体物理运动、情绪、情感和睡眠等的控制。GCH1,PCBD1,PTS,QDPR这几个基因指导合成和回收四氢生物喋呤的关键酶，这几个基因突变导致四氢生物喋呤缺乏，苯基丙氨酸在体内堆积从而对机体形成损害。
GCH1编码三磷酸鸟苷环水解酶1，该酶参与BH4生成反应的第一步。已发现140多种基因突变会导致多巴反应性肌张力障碍，表现为肌肉不随意收缩、颤动，可以通过服用左旋多巴胺来治疗；另外至少有7种突变会导致四氢蝶呤缺乏症，占比4%，苯丙氨酸无法转化为酪氨酸，有害产物堆积对机体造成毒性。
| 基因名称 | 基因全名 | 基因位置 | 外显子个数 | CDS长度 |
|---|---|---|---|---|
| GCH1 | GTP cyclohydrolase 1 | 14q22.1-q22.2 | 6 | 约2925 bp |
| 基因摘要 | This gene encodes a member of the GTP cyclohydrolase family. The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an essential cofactor required by aromatic amino acid hydroxylases as well as nitric oxide synthases. Mutations in this gene are associated with malignant hyperphenylalaninemia and dopa-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all variants give rise to a functional enzyme. [provided by RefSeq, Jul 2008]. | |||