GCLC 缺陷导致 HAGGSD
中文名称
通路描述
在哺乳动物细胞中，存在许多抗氧化防御系统，以保护细胞免受氧化应激的后续暴露。一种抗氧化剂是谷胱甘肽（GSH），一种存在于几乎所有细胞中的三肽，调节细胞内氧化还原状态并保护细胞免受氧化损伤。它通过γ-谷氨酰循环代谢，该循环由六种酶催化。在人类中，已发现五种酶的遗传缺陷。γ-谷氨酰半胱氨酸合酶（GCL）催化 GSH 生物合成的第一步和限速步骤。GCL 是一个由催化重链（GCLC）和调节轻链（GCLM）组成的异二聚体。催化 GCLC 的缺陷可导致由于γ-谷氨酰半胱氨酸合酶缺陷引起的溶血性贫血（HAGGSD；MIM:230450），这是一种以溶血性贫血、谷胱甘肽缺乏、肌病、晚期脊髓小脑萎缩和周围神经病变为特征的疾病（参见 Ristoff 和 Larsson 2007、Aoyama 和 Nakaki 2013）。
英文描述
Defective GCLC causes HAGGSD In mammalian cells, many antioxidant defence systems exist which protect cells from subsequent exposure to oxidant stresses. One antioxidant is glutathione (GSH), a tripeptide present in virtually all cells that regulates the intracellular redox state and protects cells from oxidative injury. It is metabolised via the gamma-glutamyl cycle, which is catalysed by six enzymes. In man, hereditary deficiencies have been found in five of the six enzymes. Gamma-glutamylcysteine ligase (GCL) catalyses the first and rate-limiting step in GSH biosynthesis. GCL is a heterodimer of a catalytic heavy chain (GCLC) and a regulatory light chain (GCLM). Defects in the catalytic GCLC can cause hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD; MIM:230450), a disease characterised by hemolytic anemia, glutathione deficiency, myopathy, late-onset spinocerebellar degeneration, and peripheral neuropathy (Ristoff & Larsson 2007, Aoyama & Nakaki 2013).
所含基因
1 个基因