Chou Janice Y, Kim Goo-Young, Cho Jun-Ho
Section on Cellular Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Liver Res. 2017 Sep;1(3):174-180. doi: 10.1016/j.livres.2017.12.001.
Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC) that is expressed primarily in the liver, kidney, and intestine. G6Pase-α catalyzes the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis, and is a key enzyme for endogenous glucose production. The active site of G6Pase-α is inside the endoplasmic reticulum (ER) lumen. For catalysis, the substrate G6P must be translocated from the cytoplasm into the ER lumen by a G6P transporter (G6PT). The functional coupling of G6Pase-α and G6PT maintains interprandial glucose homeostasis. Dietary therapies for GSD-Ia are available, but cannot prevent the long-term complication of hepatocellular adenoma that may undergo malignant transformation to hepatocellular carcinoma. Animal models of GSD-Ia are now available and are being exploited to both delineate the disease more precisely and develop new treatment approaches, including gene therapy.
Ia型糖原贮积病（GSD-Ia）是一种常染色体隐性代谢紊乱疾病，由葡萄糖-6-磷酸酶-α（G6Pase-α或G6PC）缺乏引起，该酶主要在肝脏、肾脏和肠道中表达。G6Pase-α在糖异生和糖原分解的终末步骤中催化葡萄糖-6-磷酸（G6P）水解为葡萄糖和磷酸，是内源性葡萄糖生成的关键酶。G6Pase-α的活性位点在内质网（ER）腔内。为了进行催化，底物G6P必须通过G6P转运体（G6PT）从细胞质转运到ER腔内。G6Pase-α和G6PT的功能偶联维持餐间葡萄糖稳态。GSD-Ia有饮食疗法，但无法预防肝细胞腺瘤的长期并发症，而肝细胞腺瘤可能会恶变为肝细胞癌。现在已有GSD-Ia的动物模型，并正在用于更精确地描述该疾病以及开发新的治疗方法，包括基因治疗。
