The core M3 O-mannosyl glycan on α-dystroglycan serves as the binding epitope for extracellular matrix molecules. Defects in core M3 glycans cause congenital muscular dystrophies that are collectively known as dystroglycanopathies. The core M3 glycan contains a tandem D-ribitol-5-phosphate (Rbo5P) structure, which is synthesized by the Rbo5P-transferases fukutin (FKTN) and fukutin-related protein (FKRP) using CDP-ribitol (CDP-Rbo) as a donor substrate. CDP-Rbo is synthesized from CTP and Rbo5P by CDP-Rbo pyrophosphorylase A (CRPPA). However, the Rbo5P biosynthesis pathway has yet to be elucidated in mammals. Here, we investigated the reductase activities toward four substrates including ribose, ribulose, ribose-phosphate, and ribulose-phosphate to identify the intracellular Rbo5P production pathway and elucidated the role of the aldo-keto reductases AKR1A1, AKR1B1, and AKR1C1 in those pathways. It was shown that the ribose reduction pathway is the endogenous pathway that contributes most to Rbo5P production in HEK293T cells and that AKR1B1 is the major reductase in this pathway.

中文翻译：

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哺乳动物中产生核糖醇磷酸（CDP-核糖醇前体）的内源性还原酶活性。

α-肌营养不良聚糖上的核心 M3 O-甘露糖基聚糖充当细胞外基质分子的结合表位。核心 M3 聚糖的缺陷会导致先天性肌营养不良症，统称为肌营养不良症。核心 M3 聚糖包含串联 D-核糖醇-5-磷酸 (Rbo5P) 结构，该结构由 Rbo5P 转移酶 fukutin (FKTN) 和 fukutin 相关蛋白 (FKRP) 使用 CDP-ribitol (CDP-Rbo) 作为合成物合成。供体底物。CDP-Rbo 由 CTP 和 Rbo5P 通过 CDP-Rbo 焦磷酸化酶 A (CRPPA) 合成。然而，哺乳动物中的 Rbo5P 生物合成途径尚未阐明。在这里，我们研究了四种底物（包括核糖、核酮糖、核糖磷酸和核酮糖磷酸）的还原酶活性，以确定细胞内 Rbo5P 生产途径，并阐明醛酮还原酶 AKR1A1、AKR1B1 和 AKR1C1 在这些途径中的作用。结果表明，核糖还原途径是对 HEK293T 细胞中 Rbo5P 产生贡献最大的内源途径，而 AKR1B1 是该途径中的主要还原酶。