Oral ingestion of mannose elevates blood mannose levels: A first step toward a potential therapy for carbohydrate-deficient glycoprotein syndrome type I
Oral ingestion of mannose elevates blood mannose levels: A first step toward a potential therapy for carbohydrate-deficient glycoprotein syndrome type I
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DOI：
10.1006/bmme.1997.2574
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发表时间：
1997-04-01
期刊：
影响因子：
--
通讯作者：
Freeze, HH
中科院分区：
文献类型：
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作者：
Alton, G;Kjaergaard, S;Freeze, HH
I 型碳水化合物缺乏糖蛋白综合征 (CDGS) 是一种遗传性代谢紊乱，由于未能将完整的 N 连接寡糖链添加到许多糖蛋白中而导致多系统异常。这些患者的成纤维细胞也异常地糖基化蛋白质，但是通过向培养基中提供250μM甘露糖可以纠正这种损害。这种蛋白质糖基化的校正表明，提供膳食甘露糖以提高血液甘露糖浓度也可能纠正这些患者中观察到的一些糖基化不足。我们发现，摄入的甘露糖可以被有效吸收，并增加正常受试者和 CDGS 患者的血液甘露糖水平。随着甘露糖口服剂量的增加（0.07-0.21克甘露糖/公斤体重），血液甘露糖水平以剂量依赖性方式增加。摄入后 1-2 小时出现血甘露糖浓度峰值，半清除时间约为 4 小时。在正常对照（类似于55μM）和CDGS患者中，以3小时间隔给予0.1g甘露糖/kg体重的剂量将血液甘露糖浓度维持在比基础水平高3至5倍的水平。该剂量方案没有观察到副作用。这些结果证实了使用甘露糖作为潜在的治疗性膳食补充剂（营养品）来治疗 CDGS 患者的可行性。 (C) 1996 年学术出版社。
Carbohydrate-deficient glycoprotein syndrome type I (CDGS) is an inherited metabolic disorder with multisystemic abnormalities resulting from a failure to add entire N-linked oligosaccharide chains to many glycoproteins. Fibroblasts hom these patients also abnormally glycosylate proteins, but this lesion is corrected by providing 250 mu M mannose to the culture medium. This correction of protein glycosylation suggests that providing dietary mannose to elevate blood mannose concentrations might also remedy some of the underglycosylation observed in these patients. We find that ingested mannose is efficiently absorbed and increases blood mannose levels in both normal subjects and CDGS patients. Blood mannose levels increased in a dose-dependent fashion with increasing oral doses of mannose (0.07-0.21 g mannose/kg body weight). Peak blood mannose concentrations occurred at 1-2 h following ingestion and the clearance half-time was approximately 4 h. Doses of 0.1 g mannose/kg body weight given at 3-h intervals maintained blood mannose concentrations at levels 3- to 5-fold higher than the basal level in both normal controls (similar to 55 mu M) and CDGS patients. No side effects were observed for this dosage regimen. These results establish the feasibility of using mannose as a potential therapeutic dietary supplement (nutraceutical) to treat CDGS patients. (C) 1996 Academic Press.