Gch在蝶啶代谢通路中参与鱼类体色形成

GTP Cyclohydrolase Functions in Fish Color Formation

鸟苷三磷酸环化水解酶(GTP cyclohydrolase,Gch)是具有GTP-cyclohydro结构域的蛋白酶,广泛存在于脊椎动物和无脊椎动物中。哺乳动物和鸟类中只具有Gch1,硬骨鱼类和两栖动物中Gch1存在旁系同源的Gch2和Gch3,且功能存在差异。Gch是以鸟苷三磷酸为底物,最终形成四氢生物蝶呤(tetrahydrobiopterin,BH4)的限速酶,而BH4是芳香族氨基酸羟化酶必须的辅助因子,参与多种激素和神经递质的合成。Gch是催化各种蝶呤生物合成的起始步骤,例如皮肤色素、眼色素、甲氨蝶呤、叶黄酸和BH4等,在体内一系列生理病理过程中发挥重要作用。Gch的生理功能与BH4的生物合成有着不可分割的联系,作为BH4生物合成的唯一限速酶,其活性可作为神经元和色素细胞的发育指示物,也是研究色素形成和神经递质生物合成的重要标志。目前,Gch在肿瘤和心血管等疾病的发病机制方面已获得广泛关注和解析,而色素合成和体色调控的作用研究多集中在昆虫方面,在硬骨鱼类中较少。因此,本文将重点对Gch基因、蛋白质、功能以及在鱼类体色方面中的作用进行总结归纳,对深入分析Gch在鱼类体色形成中的作用及后期鱼类体色改良具有重要的指导意义。

Guanosine triphosphate cyclohydrolase(GTP cyclohydrolase,Gch) is a protease with a GTP-cyclohydro domain, which is widely found in vertebrates and invertebrates. Mammals and birds only have Gch1. In teleost and amphibian, other two paralogs(Gch2 and Gch3) also exists besides Gch1, which also displayed functional differences. Gch is a rate-limiting enzyme that ultimately synthesized the tetrahydrobiopterin(BH4) using guanosine triphosphate as a substrate. BH4 is an essential coenzyme of aromatic amino acid hydroxylase and contributes to the synthesis of various hormones and neurotransmitters. The Gch is an initial step in the catalysis of various pterin biosynthesis and plays important roles in a series of physiological and pathological processes, such as skin pigmentation, ocular pigmentation, methotrexate, folic acid, and tetrahydrobiopterin. The physiological function of Gch is inextricably linked to the biosynthesis of BH4. As the only rate-limiting enzyme in BH4 biosynthesis, the activity of Gch is a useful indicator for the development of neurons and pigment cells. Besides, it is also an important marker of pigment synthesis and neurotransmitter biosynthesis. Nowadays, the functions of Gch in pathogenesis of tumor and cardiovascular diseases have been widely concerned, while the researches on the pigmentation and color formation are mainly concentrated in insects, and rarely in teleost. Therefore, this article summarized the characteristics of Gch genes, protein and the functions of Gch in fish coloration, which has important guiding significance for further illustration the mechanism of Gch in teleost pigmentation and fish color genetic improvements.