Chou Janice Y, Mansfield Brian C
Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA; Foundation Fighting Blindness, Columbia, Maryland, USA.
Curr Top Membr. 2014;73:357-82. doi: 10.1016/B978-0-12-800223-0.00010-4.
The SLC37 family members are endoplasmic reticulum (ER)-associated sugar-phosphate/phosphate (P(i)) exchangers. Three of the four members, SLC37A1, SLC37A2, and SLC37A4, function as Pi-linked glucose-6-phosphate (G6P) antiporters catalyzing G6P:P(i) and P(i):P(i) exchanges. The activity of SLC37A3 is unknown. SLC37A4, better known as the G6P transporter (G6PT), has been extensively characterized, functionally and structurally, and is the best characterized family member. G6PT contains 10 transmembrane helices with both N and C termini facing the cytoplasm. The primary in vivo function of the G6PT protein is to translocate G6P from the cytoplasm into the ER lumen where it couples with either the liver/kidney/intestine-restricted glucose-6-phosphatase-α (G6Pase-α or G6PC) or the ubiquitously expressed G6Pase-β (or G6PC3) to hydrolyze G6P to glucose and P(i). The G6PT/G6Pase-α complex maintains interprandial glucose homeostasis, and the G6PT/G6Pase-β complex maintains neutrophil energy homeostasis and functionality. G6PT is highly selective for G6P and is competitively inhibited by cholorogenic acid and its derivatives. Neither SLC37A1 nor SLC37A2 can couple functionally with G6Pase-α or G6Pase-β, and the antiporter activities of SLC37A1 or SLC37A2 are not inhibited by cholorogenic acid. Deficiencies in G6PT cause glycogen storage disease type Ib (GSD-Ib), a metabolic and immune disorder. To date, 91 separate SLC37A4 mutations, including 39 missense mutations, have been identified in GSD-Ib patients. Characterization of missense mutations has yielded valuable information on functionally important residues in the G6PT protein. The biological roles of the other SLC37 proteins remain to be determined and deficiencies have not yet been correlated to diseases.
溶质载体家族37（SLC37）成员是内质网（ER）相关的糖磷酸/磷酸（P(i)）交换体。四个成员中的三个，即SLC37A1、SLC37A2和SLC37A4，作为与磷酸（Pi）偶联的葡萄糖-6-磷酸（G6P）反向转运体，催化G6P:Pi和Pi:Pi交换。SLC37A3的活性尚不清楚。SLC37A4，更广为人知的名称是G6P转运体（G6PT），在功能和结构上都得到了广泛的表征，是该家族中表征最充分的成员。G6PT包含10个跨膜螺旋，其N端和C端均面向细胞质。G6PT蛋白在体内的主要功能是将G6P从细胞质转运到内质网腔中，在那里它与肝脏/肾脏/肠道特异性的葡萄糖-6-磷酸酶-α（G6Pase-α或G6PC）或普遍表达的G6Pase-β（或G6PC3）偶联，将G6P水解为葡萄糖和Pi。G6PT/G6Pase-α复合物维持餐后葡萄糖稳态，G6PT/G6Pase-β复合物维持中性粒细胞能量稳态和功能。G6PT对G6P具有高度选择性，并受到绿原酸及其衍生物的竞争性抑制。SLC37A1和SLC37A2在功能上均不能与G6Pase-α或G6Pase-β偶联，且SLC37A1或SLC37A2的反向转运体活性不受绿原酸抑制。G6PT缺陷会导致I型b糖原贮积病（GSD-Ib），这是一种代谢和免疫紊乱疾病。迄今为止，在GSD-Ib患者中已鉴定出91种不同的SLC37A4突变，包括39种错义突变。错义突变的表征为G6PT蛋白中功能重要的残基提供了有价值的信息。其他SLC37蛋白的生物学作用仍有待确定，且尚未发现其缺陷与疾病相关。
