A partial deficiency of dehydrodolichol reduction is a cause of carbohydrate-deficient glycoprotein syndrome type I

Takashi Ohkura, Keiko Fukushima, Akira Kurisaki, Hiroshi Sagami, Kyozo Ogura, Kousaku Ohno, Sayuri Hara-Kuge, Katsuko Yamashita

研究成果: Article

35 引用 (Scopus)

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Carbohydrate-deficient glycoprotein (CDG) syndrome type I is a congenital disorder that involves the underglycosylation of N-glycosylated glycoproteins (Yamashita, K., Ideo, H., Ohkura, T., Fukushima, K., Yuasa, I., Ohno, K., and Takeshita, K. (1993) J. Biol. Chem. 268, 5783-5789). In an effort to further elucidate the biochemical basis of CDG syndrome type I in our patients, we investigated the defect in the multi-step pathway for biosynthesis of lipid-linked oligosaccharides (LLO) by the metabolic labeling method using [3H]glucosamine, [3H]mannose, and [3H]mevalonate. The LLO levels in synchronized cultures of fibroblasts from these patients were severalfold lower than those in control fibroblasts in the S phase, and the oligosaccharides released from LLO showed the same structural composition, Glc1-3·Man9·GlcNAc·GlcNAc, in the case of both the patients and controls. The amount of [3H]mannose incorporated into mannose 6-phosphate, mannose 1-phosphate, and GDP-mannose was greater in fibroblasts from these patients than in the control fibroblasts in the G1 period, although the ratios of these acidic mannose derivatives as indicated by the relative levels of radioactivity were the same for the two types of fibroblasts. Furthermore, upon metabolic labeling with [3H]mevalonate, the level of [3H]dehydrodolichol in fibroblasts from these patients increased in the S phase, and the levels of [3H]dolichol and [3H]dolichol-PP oligosaccharides concomitantly decreased, although the chain length distribution of the respective dolichols and dehydrodolichols was the same in the two types of fibroblasts. These results indicate that the conversion of dehydrodolichol to dolichol is partially defective in our patients and that the resulting loss of dolichol leads directly to underglycosylation.

元の言語English
ページ(範囲)6868-6875
ページ数8
ジャーナルJournal of Biological Chemistry
272
発行部数11
DOI
出版物ステータスPublished - 1997 3 14

ASJC Scopus subject areas

  • Biochemistry

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    Ohkura, T., Fukushima, K., Kurisaki, A., Sagami, H., Ogura, K., Ohno, K., Hara-Kuge, S., & Yamashita, K. (1997). A partial deficiency of dehydrodolichol reduction is a cause of carbohydrate-deficient glycoprotein syndrome type I. Journal of Biological Chemistry, 272(11), 6868-6875. https://doi.org/10.1074/jbc.272.11.6868