GGT1 缺陷导致 GLUTH
中文名称
通路描述
为了在尿液中排出，谷胱甘肽共轭物经历多个水解步骤形成巯基酸，这些巯基酸易于排出。第一步是由γ-谷氨酰转移酶（GGTs）催化γ-谷氨酰残基从共轭物中的水解。这些是膜结合、异二聚体酶，由轻链和重肽链组成。细胞外谷胱甘肽（GSH）或其共轭物可水解产生半胱氨酸甘氨酸（CG，或 CG 共轭物）和游离谷氨酸（L-Glu）。GSH 的水解为细胞提供局部半胱氨酸供应并有助于细胞内 GSH 水平（参见 Heisterkamp 等 2008）。GGT1 的缺陷可导致谷胱甘肽尿症（GLUTH；MIM:231950），这是一种常染色体隐性疾病，其特征是血浆和尿液中 GSH 浓度增加。导致 GLUTH 的突变可在 GGT1 二聚体的两条链中发生（参见 Heisterkamp 等 2008、Aoyama 和 Nakaki 2013）。
英文描述
Defective GGT1 causes GLUTH To be excreted in urine, glutathione conjugates undergo several hydrolysis steps to form mercapturic acids which are readily excreted. The first step is the hydrolysis of a gamma-glutamyl residue from the conjugate catalysed by gamma-glutamyltransferases (GGTs). These are membrane-bound, heterodimeric enzymes composed of light and heavy peptide chains. Extracellular glutathione (GSH) or its conjugates can be hydrolysed to give cysteinylglycine (CG, or CG conjugates) and free glutamate (L-Glu). Hydrolysis of GSH provides cells with a local cysteine supply and contributes to intracellular GSH levels (Heisterkamp et al. 2008). Defects in GGT1 can cause glutathionuria (GLUTH; MIM:231950), an autosomal recessive disorder characterised by increased GSH concentration in the plasma and urine. Mutations that cause GLUTH can occur in both chains of the GGT1 dimer (Heisterkamp et al. 2008, Aoyama & Nakaki 2013).
所含基因
1 个基因