The Formation of Sugar Derivatives of Dolichyl Phosphate in Mammalian Systems

1973 ◽  
Vol 1 (5) ◽  
pp. 1029-1033 ◽  
Author(s):  
F. W. HEMMING
Keyword(s):  
Dolichyl Phosphate ◽  
Sugar Derivatives ◽  
Derivatives Of

scholarly journals The effect of flavomycin on the synthesis and transfer of lipid-linked saccharides in pig brain

1982 ◽  
Vol 201 (3) ◽  
pp. 481-487 ◽  
Author(s):  
Ernst Bause ◽  
Günter Legler
Keyword(s):  
Mode Of Action ◽  
Direct Interaction ◽  
Inhibitory Effects ◽  
Dolichyl Phosphate ◽  
Pig Brain ◽  
Endogenous Protein ◽  
High Concentrations ◽  
Sugar Derivatives ◽  
Competitive Nature ◽  
Derivatives Of

Particulate membrane fractions from pig brain catalyse the synthesis of lipid-linked sugar derivatives of the dolichyl phosphate pathway. Flavomycin, a phosphoglycolipid antibiotic produced by various species of streptomycetes, interferes with the formation of these glycolipids to a different extent. The formation of dolichyl phosphate glucose was shown to be most susceptible to the antibiotic, being blocked by about 50% in the presence of 0.2mm-flavomycin, whereas the synthesis of dolichyl diphosphate N-acetylglucosamine, dolichyl diphosphate chitobiose and dolichyl diphosphate chitobiosyl mannose required higher concentrations to achieve a comparable inhibition. Although the formation of dolichyl phosphate mannose was hardly affected, the accumulation of oligosaccharides with five to seven sugar units was observed, when dolichyl diphosphate oligosaccharides were synthesized with GDP-[14C]mannose in the presence of 1mm-flavomycin. This indicates that the inhibition of the synthesis of larger-sized oligosaccharides, known to be mediated by lipid-bound mannose, was not caused by an actual deficiency in dolichyl phosphate mannose. At flavomycin concentrations that inhibited the formation of dolichyl phosphate glucose by 50%, the transfer of lipid-linked saccharides to either the hexapeptide Tyr-Asn-Gly-Thr-Ser-Val or endogenous protein acceptors was hardly influenced. The mode of action of flavomycin is still obscure, but seems not to be of a competitive nature, since the inhibition was unaffected by increasing concentrations of dolichyl phosphate. Some evidence indicates that, besides a direct interaction of the antibiotic with some transferases, a non-specific incorporation into the membrane and alteration of its properties might be responsible for those inhibitory effects on all enzymes which were observed at high concentrations of flavomycin.

Glomerular uracil nucleotide synthesis

1988 ◽  
Vol 255 (4) ◽  
pp. F635-F646 ◽  
Author(s):  
P. Cortes ◽  
F. Dumler ◽  
N. W. Levin
Keyword(s):  
Protein Glycosylation ◽  
Rapid Rate ◽  
Membrane Material ◽  
Nucleotide Synthesis ◽  
Initial Concentration ◽  
High Initial Concentration ◽  
Uracil Nucleotide ◽  
Sugar Derivatives ◽  
Derivatives Of

The biosynthesis of basement membrane material requires the sugar derivatives of uridine 5'-triphosphate (UTP) for protein glycosylation. Uridine and orotate utilization for the biosynthesis of uracil ribonucleotides was studied in isolated rat glomeruli incubated in vitro. At a 1 microM concentration total orotate utilization was 9.6 +/- 1.8 pmol.min-1.mg DNA-1 (1 mg DNA approximately 0.175 X 10(6) glomeruli), 51% of the total amount metabolized was used in ribonucleotide formation, and there was a significant UTP accretion. Except at a high initial concentration (50 microM), exogenous uridine failed to increase the UTP pool due to rapid uridine breakdown by a cytosolic phosphorylase. Inhibition of this enzyme with benzylacyclouridine resulted in increased biosynthesis and accretion of UTP, and in a 17-fold higher concentration of uridine, primarily produced from performed sources of nucleosides. Continuous addition of exogenous uridine to maintain its concentration at 1 microM resulted in a total uridine utilization of 550 +/- 30 pmol.min-1.mg DNA-1. Uridine salvage for ribonucleotide biosynthesis was only 3% of the total metabolized. In contrast to uridine, and presumably due to UTP pool compartmentation, orotate incorporation into uridine 5'-diphosphosugars was prominent. The metabolism of exogenous orotate was not decreased by the presence of large amounts of uridine and by an expanded UTP pool. It is concluded that when exogenous orotate is present, it is an important precursor for glomerular uracil ribonucleotide biosynthesis. Due to its rapid rate of catabolism, uridine cannot maintain ribonucleotide biosynthesis at a rate sufficient to result in UTP accretion unless it is provided continuously in substantial quantities.

SYNTHESIS OF AMINOACYL SUGAR DERIVATIVES AND THEIR TASTE CHARACTERISTICS. I. 2,3-DI- O-AMINOACYL DERIVATIVES OF ALKYL d-GLUCOPYRANOSIDES

2002 ◽  
Vol 21 (1-2) ◽  
pp. 131-142 ◽  
Author(s):  
Tomoya Machinami ◽  
Norihiro Iibuchi ◽  
Takushi Nomura ◽  
Takeshi Mitsumori ◽  
Tetsuo Suami ◽  
...  
Keyword(s):  
Sugar Derivatives ◽  
Derivatives Of

scholarly journals 8-Hydroxyquinoline Glycoconjugates: Modifications in the Linker Structure and Their Effect on the Cytotoxicity of the Obtained Compounds

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4181 ◽  
Author(s):  
Monika Krawczyk ◽  
Gabriela Pastuch-Gawołek ◽  
Aleksandra Pluta ◽  
Karol Erfurt ◽  
Adrian Domiński ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cytotoxic Effect ◽  
Copper Ions ◽  
Nitrogen Heterocycles ◽  
Anti Cancer ◽  
Hct 116 ◽  
Complexing Properties ◽  
Sugar Derivatives ◽  
Derivatives Of ◽  
Mcf 7

Small molecule nitrogen heterocycles are very important structures, widely used in the design of potential pharmaceuticals. Particularly, derivatives of 8-hydroxyquinoline (8-HQ) are successfully used to design promising anti-cancer agents. Conjugating 8-HQ derivatives with sugar derivatives, molecules with better bioavailability, selectivity, and solubility are obtained. In this study, 8-HQ derivatives were functionalized at the 8-OH position and connected with sugar derivatives (D-glucose or D-galactose) substituted with different groups at the anomeric position, using copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC). Glycoconjugates were tested for inhibition of the proliferation of cancer cell lines (HCT 116 and MCF-7) and inhibition of β-1,4-galactosyltransferase activity, which overexpression is associated with cancer progression. All glycoconjugates in protected form have a cytotoxic effect on cancer cells in the tested concentration range. The presence of additional amide groups in the linker structure improves the activity of glycoconjugates, probably due to the ability to chelate metal ions present in many types of cancers. The study of metal complexing properties confirmed that the obtained glycoconjugates are capable of chelating copper ions, which increases their anti-cancer potential.

Polyprenyl phosphates as coenzymes in protein and oligosaccharide glycosylation

1978 ◽  
Vol 284 (1002) ◽  
pp. 559-568 ◽  
Keyword(s):  
En Bloc ◽  
Plant Kingdom ◽  
Green Plants ◽  
Dolichyl Phosphate ◽  
Membrane Bound ◽  
Sugar Derivatives ◽  
Polyprenyl Phosphates ◽  
Algal Cellulose

Partly saturated polyprenols of the dolichol type occur in all branches of the plant kingdom although in green plants they are quantitatively minor compared with the shorter polyprenols of the ficaprenol and betulaprenol type. Nevertheless, in all members of the plant kingdom so far studied it is the dolichyl phosphates that function in glycosyl transfer. In yeasts, dolichyl phosphate mannose is primarily an intermediate in the O-mannosylation of some membrane-bound proteins. Further mannosylation of the mannoprotein does not involve dolichyl phosphate. Yeast membrane preparations also catalyse the sequential transfer from the appropriate nucleoside diphosphate sugar of N -acetylglucosaminyl phosphate, N -acetylglucosamine, several mannose residues and several glucose residues to dolichyl monophosphate to form a dolichyl diphosphate oligosaccharide. The oligosaccharide is then transferred en bloc to protein to form an N-glycosidically linked glycoprotein. The transfer of mannose and glucose to the dolichyl diphosphate oligosaccharide is probably via dolichyl monophosphate sugar derivatives. Tunicamycin inhibits specifically the transfer of JV-acetylglucosamine phosphate which in turn blocks protein N-glycosylation. Evidence for corresponding processes in O- and N-glycosylation of proteins of hyphal fungi is also available but much less well established. The N-glycosylation of proteins by membrane preparations of green plants appears to occur by a process very similar to that found in yeast. In addition, the biosynthesis of β1-3 and β1-4 linked oligoglucans and also of an algal cellulose primer (a glucoprotein) via dolichyl phosphate glucose has been reported. Possible consequences of these phenomena are discussed.

Towards a Simultaneous and Harmonized Regulation of Haemostasis and of the Cardiovascular System

1979 ◽  
Author(s):  
L. Mester ◽  
L. Szabados ◽  
J.M. Launay ◽  
M. Mester
Keyword(s):  
Cardiovascular System ◽  
Smooth Muscle Contraction ◽  
New Approach ◽  
Physiological Conditions ◽  
Spontaneous Formation ◽  
Vascular Smooth Muscle Contraction ◽  
Sugar Derivatives ◽  
Derivatives Of ◽  
Regulation Of Blood Pressure ◽  
Platelet Functions

I-Desoxy-l-(5-hydroxytryptamino)-D-fructose is a synthetic sugar derivative of serotonin, however, its spontaneous formation under physiological conditions is quite possible (5th Inter. Congr. Thromb. Haemost., Paris, 1975, Abstr. n°233). This, and similar sugar derivatives of serotonin show a serotonin-like activity, however, a discrepancy has been observed between their affinities towards D and M type tryptaminergic receptors, when compared with the affinity of serotonin for the same receptors. The sugar derivatives have been distinguished by an increased passage of the blood-brain barrier and by a limited uptake by theplatelet. They exhibit a mechanism which mildly inhibits platelet functions, while mildly supporting haemostasis by vascular smooth muscle contraction. Besides the regulation of blood pressure, heart rate and sinusal coronary flow, some typical central effects (anti-stress activity, suppression of the carotid occlusion response, etc.) have also been observed, which have a beneficial effect on the cardiovascular system. Progressing in this way, it is hoped to have a new approach to inhibiting thrombosis without significantly interfering with haemostasis.

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