The role of dolichol monophosphate in sugar transfer

Behrens, Nicolas; Parodi, Armando J.; Leloir, Luis F.; Krisman, Clara R.

doi:10.1016/0003-9861(71)90224-4

Cited by 127 publications

(41 citation statements)

References 19 publications

(8 reference statements)

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“…III addition, the chemical and chromatographic properties of the mannolipid are comparable to those of synthetic dolichol-monophosphate-mannose prepared according to Behrens, Leloir et al (16,32 reached a plateau after al)proximately 5 min of incubation in the presence of less than 10 pM GDP-mannosc.…”

Section: Richards and Hemming (8) Have Demonstratedsupporting

confidence: 61%

“…These results suggest that the lipid is a form of dolichol (15), a C-100 a-saturated polyisoprenol, which, as dolichol monophosphate, has been characterized as a glgcosyl acceptor in liver microsomes by Lcloir (16,32), and Hemming (8), and their co-workers.…”

Section: Richards and Hemming (8) Have Demonstratedmentioning

confidence: 93%

“…It is not yet clear whether the same lipid or distinct members of a family of isoprcnoid lipids function as carriers for different sugars, but there is strong evidence indicating that both glucose (16,32,45) and A-acetylglucosamine (46-48) are transferred to protein through glycolipid intermediates.…”

mentioning

confidence: 99%

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The Role of Mannosyl Phosphoryl Dihydropolyisoprenol in the Synthesis of Mammalian Glycoproteins

Heath¹,

Baynes²,

Hsu³

1974

Biology and Chemistry of Eukaryotic Cell Surfaces

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Section: Richards and Hemming (8) Have Demonstratedsupporting

confidence: 61%

Section: Richards and Hemming (8) Have Demonstratedmentioning

confidence: 93%

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The Role of Mannosyl Phosphoryl Dihydropolyisoprenol in the Synthesis of Mammalian Glycoproteins

Heath¹,

Baynes²,

Hsu³

1974

Biology and Chemistry of Eukaryotic Cell Surfaces

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“…In the case of glucose the microsomal enzymes of the liver catalyze the transfer of the monosaccharide from UDPglucose to dolichol monophosphate [ l-3). Behrens et al [3] also tried UDP~ucuronic acid (UDPGlcUA) as donor, but found very little incorporation with natural dolichol monophosphate and none with synthetic polyprenol. Winsnes [7] failed to find a GlcUA carrier in the glucuronidation of 'L-aminophenol.…”

Section: Introductionmentioning

confidence: 99%

Lipid acceptor in udpglucuronic acid metabolism in rat liver microsomes

Puhakainen

Hänninen

1974

FEBS Letters

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“…Since it is well established in a variety of systems in vitro that supplementation with dolichyl phosphate leads to enhanced glycosylation (e.g. [5,6]), it has been suggested that inhibition of oligosaccharide-lipid synthesis in cells arrested in protein synthesis results because of a deficiency in dolichyl phosphate [3,4]. Such deficiency might occur in the absence of synthesis of acceptor polypeptides, since the lack of transfer of the oligosaccharide chain from the oligosaccharide-lipid to the acceptor polypeptide would preclude concomitant regeneration of dolichyl (di)phosphate.…”

mentioning

confidence: 99%

Relationship between Oligosaccharide‐Lipid Synthesis and Protein Synthesis in Mouse LM Cells

Grant

Lennarz

1983

European Journal of Biochemistry

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Previous studies from several laboratories have reported that inhibition of protein synthesis results in a concomitant reduction in synthesis of oligosaccharide-diphosphoryldolichol. We have investigated this phenomenon in LM cells grown in defined culture medium. The results of this study indicate that incubation of LM cells with cycloheximide at a concentration sufficient to totally arrest polypeptide synthesis, results in a rapid reduction in the synthesis of [3H]mannose-labeled or [3H]glucosamine-labeled oligosaccharide-lipid within 2 min. Cycloheximide treatment had only a slight inhibitory effect on synthesis of GDP-Man. Furthermore, during the first 5 min after the addition of cycloheximide to L a cells, when [3H]mannose incorporation into oligosaccharidelipid was maximally reduced, the specific activity of the GDP-Man pool was identical to that observed in control cells. Labeling in vivo of the lipid-linked saccharide precursors of oligosaccharide-lipid revealed that cycloheximide had virtually no effect on the synthesis of Man-P-Dol, GlcNAc-PP-Dol, GlcNAcz-PP-Dol, and fLMan-(GlcNAc)z-PP-Dol (Do1 = dolichol). In agreement with this finding, results of experiments in vitro using microsomes prepared from LM cells indicate that cycloheximide did not directly inhibit the enzymes responsible for the synthesis of these lipid-linked saccharide precursors.Supplementation of mouse LM cells by preincubation for 1 h with dolichyl phosphate (5 pg/ml) resulted in a 300 % stimulation of oligosaccharide-lipid synthesis when compared to non-supplemented cells. However, dolichyl phosphate supplementation of cycloheximide-treated cells failed to restore oligosaccharide-lipid synthesis to the level observed in control cells. In control cells pre-labeled oligosaccharide-lipid turned over rapidly and, as expected, cycloheximide addition to the chase medium significantly retarded this turnover process. However, preincubation of cells with exogenous dolichyl phosphate had little or no effect on the turnover of oligosaccharide-lipid in control or cycloheximide-treated cells. These findings argue against dolichyl phosphate deficiency as the primary cause of reduced oligosaccharide-lipid synthesis when protein synthesis is blocked. The implications of these results, and an alternative hypothesis to explain the effect of inhibition of protein synthesis on oligosaccharide-lipid synthesis based on elevation of intracellular GTP levels, are discussed.Recently, several laboratories [l -41 have reported that inhibition of protein synthesis by a variety of drugs leads to inhibition of the incorporation of t3H] Man into oligosaccharide-PP-Dol. It seems likely that the mechanism of this inhibitory effect is related to regulation for N-linked glycosylation, since the various drugs employed [l -41 inhibit protein synthesis by different modes of action. Since it is well established in a variety of systems in vitro that supplementation with dolichyl phosphate leads to enhanced glycosylation (e.g. [5,6]), it has been suggested that inhibition ...

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The role of dolichol monophosphate in sugar transfer

Cited by 127 publications

References 19 publications

The Role of Mannosyl Phosphoryl Dihydropolyisoprenol in the Synthesis of Mammalian Glycoproteins

The Role of Mannosyl Phosphoryl Dihydropolyisoprenol in the Synthesis of Mammalian Glycoproteins

Lipid acceptor in udpglucuronic acid metabolism in rat liver microsomes

Relationship between Oligosaccharide‐Lipid Synthesis and Protein Synthesis in Mouse LM Cells

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