Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GLUCURONIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,117 records · Page 62Linked to original sources
PubMed1997

Simultaneous quantitative determination of the major phase I and II metabolites of ibuprofen in biological fluids by high-performance liquid chromatography on dynamically modified silica.

Ibuprofen has previously, after ingestion by man, been demonstrated to yield four major phase I metabolites, which are excreted in the urine partly as glucuronic acid conjugates. However, in previous investigations the quantitative determinations of the conjugates were performed by indirect methods. The purpose of the present investigation was to develop a high-performance liquid chromatographic (HPLC) system for the simultaneous determination of the major phase I and II metabolites of ibuprofen in biological fluids. The separation was performed using bare silica dynamically modified with N-cetyl-N,N,N-trimethylammonium hydroxide ions contained in the mobile phase. The separation of the metabolites of ibuprofen is greatly improved with this system compared to other published reversed-phase HPLC systems intended for the same purpose. The method developed makes it possible to simultaneously determine the intact glucuronic acid conjugates of ibuprofen as well as its phase I metabolites in human urine. In a study involving four healthy volunteers, a total recovery in urine of the dose given was found to be 58-86% within 8 h. This may be compared to an average of 67% earlier reported in the literature.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Stimulation of phagocytosis and phagosome-lysosome fusion by glycosphingolipids from Sphingomonas paucimobilis.

Sphingomonas paucimobilis, a Gram-negative opportunistic pathogen, is actively phagocytosed by human peripheral polymorphonuclear leukocytes (PMN) in vitro. However, when live or killed cells were delipidated, the phagocytic rate was clearly decreased. Therefore, we have investigated the physiological role of membrane lipids in phagocytic processes. S. paucimobilis type strain 2395 produces four classes of acidic glycosphingolipids (GL-1, GL-2, GL-3, and GL-4) with the common components of glucuronic acid, 2-hydroxy myristic acid and d18:0 or d21:1 long-chain base. The effect of acidic glycosphingolipids on phagocytosis by PMN using killed Staphylococcus aureus cells coated with glucuronosyl ceramide (GL-1) or ceramide tetrahexoside (GL-4) was also examined. The rate of phagosome-lysosome fusion by PMN was determined by counting acridine orange-stained bacteria under a fluorescence microscope. Both phagocytosis and phagosome-lysosome fusion by PMN of glycosphingolipid-coated bacteria were stimulated markedly in a dose-dependent manner. It was noted that GL-1 or GL-4 stimulated phagosome-lysosome fusion dramatically, but synthetic lipid A did not. Superoxide anion release from PMN was enhanced significantly by the coating with synthetic lipid A at higher concentration, but only slightly with GL-1 or GL-4. Glucuronic acid was an inhibitor of phagocytosis of GL-1-coated S. aureus by PMN. The effect of acidic glycosphingolipids obtained from mammalian tissue on phagocytosis was also compared with that of bacterial glycosphingolipids. Ganglioside GM3 and sulfatide showed a marked stimulative activity for phagocytosis by PMN, while the neutral glycosphingolipids did not. Thus, bacterial acidic glycosphingolipid and mammalian acidic glycosphingolipid promote phagocytosis and phagosome-lysosome fusion by PMN.

Glycosphingolipids↗
PubMed2004

Heparins and heparinoids: occurrence, structure and mechanism of antithrombotic and hemorrhagic activities.

The correlation between structure, anticlotting, antithrombotic and hemorrhagic activities of heparin, heparan sulfate, low molecular weight heparins and heparin-like compounds from various sources that are in used in clinical practice or under development is briefly reviewed. Heparin-like molecules composed exclusively of iduronic acid 2-O-sulfate residues have weak anticlotting activities, whereas molecules that contain both iduronic acid 2-O sulfate, iduronic acid and small amounts of glucuronic acid, such as heparin, or mixed amounts of glucuronic and iduronic acids (mollusk heparins) possess high anticlotting and anti-Xa activities. These results also suggest that a proper combination of these elements might produce a strong antithrombotic agent. Heparin isolated from shrimp mimics the pharmacological activities of low molecular weight heparins. A heparan sulfate derived from bovine pancreas and a sulfated fucan from brown algae have a potent antithrombotic activity in arterial and venous thrombosis model "in vivo" with a negligible activity upon the serine-proteases of the coagulation cascade "in vitro". These and other results led to the hypothesis that antithrombotic activity of heparin and other antithrombotic agents is due at least in part by their action on endothelial cells stimulating the synthesis of an antithrombotic heparan sulfate. All the antithrombotic agents derived from heparin and other heparinoids have hemorrhagic activity. Exceptions to this are a heparan sulfate from bovine pancreas and a sulfated fucan derived from brown algae, which have no hemorrhagic activity but have high antithrombotic activities "in vivo". Once the structure of these compounds are totally defined it will be possible to design an ideal antithrombotic.

Animals↗
PubMed1989

Kinetics of excretion of 2-acetylaminofluorene in normal and xenobiotic-treated rats and in rats with hepatocyte nodules.

This study was designed to explore further the hypothesis that the special resistance phenotype seen in hepatocyte nodules during liver carcinogenesis could have a physiologic correlate in the manner with which a carcinogenic xenobiotic is handled. Hepatocyte nodules were induced in male rats by continuous or intermittent exposure to dietary 2-acetylaminofluorene over a 25-week period. Two or 5 weeks after the exposure, the animals were given a single dose of 9-14C-2-acetylaminofluorene. The amounts and rates of excretion of unconjugated compound and derivatives and of the glucuronic acid metabolites in the bile and urine and the amounts in the blood and liver were measured over a period of 180 minutes. For comparison, animals fed the basal diet alone, animals injected with phenobarbital or 3-methylcholanthrene, animals receiving a single dose of cobalt heme and animals fed the 2-acetylaminofluorene for only 2 weeks were studied. These groups were used as controls for different patterns of drug metabolism, especially relating to the cytochromes P-450. The nodule-bearing animals showed a pattern of handling of the carcinogen that is quite different than that of the animals of any other group. They excreted in the bile plus urine from 20 to 30% less. However, relatively much more was in the urine. The free and glucuronide-conjugated metabolic products of the carcinogen were assessed by high performance liquid chromatography. The nodule-bearing animals and the animals treated with 3-methylcholanthrene excreted much more glucuronic acid esters. The pattern of distribution of labeled 2-acetylaminofluorene is different in the nodule-bearing rats than in other animals in which variations in phase I and phase II drug-metabolizing enzymes were induced by treatment with cobalt heme, phenobarbital, 3-methylcholanthrene or short-term exposure to dietary 2-acetylaminofluorene.

2-Acetylaminofluorene↗
PubMed1985

Chemical characterization of capsular polysaccharide from Cryptococcus neoformans serotype A-D.

During a study of serotyping of Cryptococcus neoformans, we found that the type strain of C. neoformans (CBS 132) was serotype A-D. This strain agglutinated with both factor 7 serum (specific for serotype A) and factor 8 serum (specific for serotype D) in our serotyping system. Therefore, we investigated the chemical structure of the antigenic capsular polysaccharide of this strain. The soluble capsular polysaccharide was obtained from the culture supernatant fluid by precipitation with ethanol. Column chromatography of the polysaccharide on DEAE-cellulose yielded three fractions (F-1 to F-3). The major antigenic activity was found in the F-3 fraction. The results obtained by methylation analysis, controlled Smith degradation-methylation analysis, partial acid hydrolysis, and other structural studies of F-3 polysaccharide indicated that the polysaccharide contains mannose, xylose, and glucuronic acid at a ratio of 7:2:2, and has a backbone of alpha (1-3)-linked D-mannopyranoside residues with a single branch of beta (1-2)-xylose and glucuronic acid. The ratio of mannose residues with or without a branch in the F-3 polysaccharide was 4:3 and its molecular weight calculated from the average of the degree of polymerization was 46,500 daltons. These results indicate that the chemical structure of the capsular polysaccharide of serotype A-D is very similar to those from serotypes A and D, suggesting that small differences in the molar ratio and pattern of linkage of monosaccharides in the branch of the polysaccharides of the three serotypes may be responsible for their different specificities.

Antigens, Bacterial↗
PubMed2006

Cytokines and proteoglycans: an introductory overview.

The defining characteristic of the glycoproteins known as proteoglycans is the presence of O-linked acidic polysaccharides known as GAGs (glycosaminoglycans). The backbone of these linear polysaccharides is a repeating disaccharide, comprising N-acetyl hexosamine alternating with beta-D-glucuronic acid, alpha-L-iduronic acid, or galactose. For some GAGs, partial deacetylation, epimerization of glucuronic acid, and substitution with N- and O-sulphates result in highly complex, heterogeneous structures. The interactions with proteins through which GAGs exert their biological effects depend on the resulting sequences. Some proteins, for example antithrombin, have highly specific sequence requirements for their GAG ligand [in this case heparin or HS (heparan sulphate)]; others, for example the fibroblast growth factors, are less demanding. GAGs, in particular HS, play a role as co-receptors for some cytokines. In addition, HS is thought to be important for the localization of cytokines, acting both as a tissue store and as a mediator of morphogen gradient formation in development. The structural determinants of GAG-cytokine interactions are therefore clearly important to understanding the biology of development, wound healing and the immune system. No single paradigm has been identified for such interactions, and the search for general principles underlying involvement of GAGs in cytokine function is at an early stage.

Animals↗
PubMed1985

Studies on monovalent anaphylactogens: evidence for a minimal size of the carbohydrate auxiliary group.

N-[6-(DNCP-amino)hexanoyl]-beta-D-glucopyranosylamine was synthesized and was found to be unable to elicit DNCP-specific passive cutaneous anaphylaxis in the guinea pig. This contrasts with the considerable anaphylactogenicity of N1,N5-bis[2-deoxy-beta-D-glucopyranos-2-yl]-N2-[N3-DNCP-beta -alanyl]glutaminamide which likewise carries a single DNCP haptenic group but a larger carbohydrate moiety, comprised of two glucopyranosylamine groups instead of one. It is concluded that monovalent anaphylactogens, carrying in addition to the haptenic part a carbohydrate auxiliary group, generally require carbohydrate moieties larger than a single monosaccharide unit in order to be effective. Metabolic glucuronic acid conjugation will, therefore, not transform an inactive monovalent hapten into an anaphylactogen when only one glucuronic acid residue is attached.

Anaphylaxis↗
PubMed2004

Characterization of human UDP-glucose dehydrogenase. CYS-276 is required for the second of two successive oxidations.

UDP-glucose dehydrogenase (UGDH) catalyzes two oxidations of UDP-glucose to yield UDP-glucuronic acid. Pathological overproduction of extracellular matrix components may be linked to the availability of UDP-glucuronic acid; therefore UGDH is an intriguing therapeutic target. Specific inhibition of human UGDH requires detailed knowledge of its catalytic mechanism, which has not been characterized. In this report, we have cloned, expressed, and affinity-purified the human enzyme and determined its steady state kinetic parameters. The human enzyme is active as a hexamer with values for Km and Vmax that agree well with those reported for a bovine homolog. We used crystal coordinates for Streptococcus pyogenes UGDH in complex with NAD+ cofactor and UDP-glucose substrate to generate a model of the enzyme active site. Based on this model, we selected Cys-276 and Lys-279 as likely catalytic residues and converted them to serine and alanine, respectively. Enzymatic activity of C276S and K279A point mutants was not measurable under normal assay conditions. Rate constants measured over several hours demonstrated that K279A continued to turn over, although 250-fold more slowly than wild type enzyme. C276S, however, performed only a single round of oxidation, indicating that it is essential for the second oxidation. This result is consistent with the postulated role of Cys-276 as a catalytic residue and supports its position in the reaction mechanism for the human enzyme. Lys-279 is likely to have a role in positioning active site residues and in maintaining the hexameric quaternary structure.

Binding Sites↗
PubMed1999

Meristem-localized inducible expression of a UDP-glycosyltransferase gene is essential for growth and development in pea and alfalfa.

PsUGT1, which encodes a microsomal UDP-glucuronosyltransferase, was cloned from root tips of Pisum sativum. PsUGT1 expression is correlated with mitosis and strongly induced in dividing cells. A region at the C terminus of the encoded protein is closely related to the UDP-glucuronic acid binding site consensus sequence, and the protein encoded by PsUGT1 catalyzes conjugation of UDP-glucuronic acid to an unknown compound. Overexpression of PsUGT1 sense mRNA has no detectable effect on transgenic pea hairy root cultures or regenerated alfalfa. However, inhibiting PsUGT1 expression by the constitutive expression of antisense mRNA (under the control of the cauliflower mosaic virus 35S promoter) markedly retards growth and development of transgenic alfalfa. Cell structure and organization in the antisense plants are similar to those of controls, but plant growth is reduced and development is delayed. This inhibition in growth is correlated with a twofold delay in the time required for completion of a cell cycle and with a >99% inhibition of border cell production. Inhibition of PsUGT1 expression by meristem-localized inducible expression of PsUGT1 antisense mRNA (under the control of its own promoter) is lethal both in pea hairy roots and in transgenic alfalfa plants. These results indicate that PsUGT1 expression is required for normal plant growth and development, and they are consistent with the hypothesis that this UDP-glycosyltransferase regulates activity of a ligand(s) needed for cell division.

Amino Acid Sequence↗
PubMed1999

Regio- and Stereoselective Synthesis of beta-D-Gluco-, alpha-L-Ido-, and alpha-L-Altropyranosiduronic Acids from Delta(4)-Uronates.

The stereoselective synthesis of beta-D-glucopyranosiduronic, alpha-L-idopyranosiduronic, and alpha-L-altropyranosiduronic acids has been performed from different Delta(4)-uronate monosaccharides. Bromination of the C-4,5 double bond provided the trans-diaxial bromohydrin derivatives, which were converted to the corresponding epoxides in high yields. Direct reduction of the epoxides using borane-tetrahydrofuran complex led to the corresponding glucuronic acids in low to good yields. Glucuronic acids were also obtained in satisfactory yields through a two-steps procedure involving bromination of the epoxide with titanium(IV) bromide followed by reduction using tributyltin hydride. Lewis acid-catalyzed rearrangement of these epoxides led to the corresponding alpha-L C-4 ketopyranosides adopting the (1)C(4) chair conformation. Hydride reduction afforded the alpha-L-idopyranosiduronic or the alpha-L-altropyranosiduronic acids, the stereoselectivity of the reduction being controlled by the appropriate substitution pattern.

Journal Article↗
PubMed1991

The structure of the O-specific polysaccharide chain of Proteus penneri strain 16 lipopolysaccharide.

O-Specific polysaccharide was obtained by mild acid degradation of Proteus penneri strain 16 lipopolysaccharide and found to contain D-glucose, D-glucuronic acid, 2-acetamido-2-deoxy-D-glucose, and 3,6-dideoxy-3-[(R)-3-hydroxybutyramido]- D-galactose in the ratio of 2:1:1:1 as well as a small proportion of O-acetyl groups. On the basis of one-dimensional 1H-NMR13C-NMR and NOE spectroscopy, two-dimensional homonuclear-shift-correlated spectroscopy with one-step and two-step relayed coherence transfer and heteronuclear 1H/13C NMR shift-correlated spectroscopy, it was concluded that the O-specific polysaccharide of P. penneri strain 16 has the following structure: (formula; see text) This structure was confirmed by methylation analysis and structural analysis of a linear tetrasaccharide fragment prepared by cleavage of the polysaccharide with anhydrous hydrogen fluoride followed by conversion of the alpha-tetrosyl fluoride obtained in to the corresponding free oligosaccharide and alditol. O-Acetyl groups were tentatively located at position 3 of the glucuronic acid residue and at position 4 of the 6-substituted glucose residue, the degree of acetylation being less than 20% of the total. Cross-reactions of P. penneri strain 16 anti-(O-specific polysaccharide) antiserum with lipopolysaccharides from several other Proteus strains and the role of 3,6-dideoxy-3-(R)-3-hydroxybutyramido-D-galactose in the serological specificity of P. penneri strain 16 are discussed.

Carbohydrate Conformation↗
PubMed1995

(S)oxazepam glucuronidation is inhibited by ketoprofen and other substrates of UGT2B7.

1,4-Benzodiazepine anxiolytics such as diazepam and halazepam are converted in vivo to oxazepam, an active metabolite with a hydroxyl group at the asymmetric C3 position. D-glucuronic acid couples with the C3 hydroxyl group of oxazepam to form pharmacologically inactive diastereomeric glucuronide conjugates. Conjugation with glucuronic acid is catalysed by the microsomal UDP-glucuronosyltransferase (UGT) enzyme system, which includes an undetermined number of isozymes. Although 1,4-benzodiazepines are ultimately cleared as oxazepam glucuronide, little is known about the particular UGT isozyme(s) responsible for the conjugation at the C3 position of these molecules. Microsomal preparations from three human livers were used to study the glucuronidation of (R,S)oxazepam in vitro. The predominant formation of the S- over the R-glucuronide was reflected by the kinetic parameters: For (S)oxazepam glucuronide, the constants were Km = 0.18 +/- 0.02 mM and Vmax = 202.6 +/- 25.0 nmol min-1 per mg protein; for (R)oxazepam glucuronide, they were Km = 0.22 +/- 0.02 mM, Vmax = 55.4 +/- 9.5 nmol min-1 per mg protein. Inhibition studies suggest that the two diastereomeric glucuronidations are catalysed by different UGT isozymes. That is, there was competitive inhibition of (S)oxazepam glucuronidation by non-steroidal anti-inflammatory drugs (NSAIDs), including ketoprofen while (R)oxazepam glucuronidation was not equally inhibited by these compounds. The order of potency of inhibitors of (S)oxazepam glucuronidation in this study was the same as the rank order of substrates conjugated by UGT2B7; hyodeoxycholic acid, estriol, (S)naproxen, ketoprofen, ibuprofen, fenoprofen, clofibric acid, and morphine (in descending order). The inhibition profile of (S)oxazepam glucuronidation suggests that UGT2B7 is the catalysing enzyme.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Tandem mass spectrometric determination of the 4S/6S sulfation sequence in chondroitin sulfate oligosaccharides.

Chondroitin sulfate (CS) is a glycosaminoglycan consisting of repeating uronic acid, N-acetylgalactosamine sulfate disaccharide units [-UroA(beta1,3)-GalNAcS(beta1,4)]n. Chondroitin sulfate type A (CSA) contains glucuronic acid, and 90% of the GalNAc residues are sulfated at the 4-position with 10% at the 6-position. Chondroitin sulfate type C (CSC) contains glucuronic acid, and 90% of the GalNAc residues are sulfated at the 6-position with 10% sulfated at the 4-position. These molecules are fragile due to their high degree of sulfation and are challenging to analyze as a result. This work presents the first evidence that tandem mass spectrometry can be used for the determination of a CS oligosaccharide sequence with respect to the positions of GalNAc sulfation. Using this technique, it is possible to analyze individual components from mixtures, saving much purification effort. Oligosaccharides produced from CSA and CSC are used in this work to demonstrate that CID MS/MS can be used to distinguish positional sulfation isomers. For charge states where charge equals the number of sulfates, abundant odd-numbered Bn and Yn ions are observed. The percent total ion abundances of these ions indicate the position of sulfation.

Carbohydrate Sequence↗
PubMed2005

Partial characterization and anticoagulant activity of a heterofucan from the brown seaweed Padina gymnospora.

The brown algae Padina gymnospora contain different fucans. Powdered algae were submitted to proteolysis with the proteolytic enzyme maxataze. The first extract of the algae was constituted of polysaccharides contaminated with lipids, phenols, etc. Fractionation of the fucans with increasing concentrations of acetone produced fractions with different proportions of fucose, xylose, uronic acid, galactose, and sulfate. One of the fractions, precipitated with 50% acetone (v/v), contained an 18-kDa heterofucan (PF1), which was further purified by gel-permeation chromatography on Sephadex G-75 using 0.2 M acetic acid as eluent and characterized by agarose gel electrophoresis in 0.05 M 1,3 diaminopropane/acetate buffer at pH 9.0, methylation and nuclear magnetic resonance spectroscopy. Structural analysis indicates that this fucan has a central core consisting mainly of 3-beta-D-glucuronic acid 1-> or 4-beta-D-glucuronic acid 1 ->, substituted at C-2 with alpha-L-fucose or beta-D-xylose. Sulfate groups were only detected at C-3 of 4-alpha-L-fucose 1-> units. The anticoagulant activity of the PF1 (only 2.5-fold lesser than low molecular weight heparin) estimated by activated partial thromboplastin time was completely abolished upon desulfation by solvolysis in dimethyl sulfoxide, indicating that 3-O-sulfation at C-3 of 4-alpha-L-fucose 1-> units is responsible for the anticoagulant activity of the polymer.

Anticoagulants↗
PubMed1986

Isolation and purification of rat liver morphine UDP-glucuronosyltransferase.

A UDP-glucuronosyltransferase (UDPGT) isoenzyme capable of morphine glucuronidation has been purified to apparent homogeneity and partially characterized from hepatic microsomes of female Wistar rats which have low 3 alpha-hydroxysteroid UDPGT. A rapid and sensitive assay was developed to quantify morphine glucuronide formation using 14C-UDP-glucuronic acid and reverse phase C-18 minicolumns whereby radioactive glucuronides were differentially eluted from 14C-UDP-glucuronic acid. Trisacryl-DEAE and chromatofocusing chromatographic procedures were employed to separate and purify morphine UDPGT in the presence of exogenous phosphatidylcholine. The addition of phospholipid was necessary to stabilize UDPGT activities throughout the purification procedures. Morphine UDPGT was isolated to apparent homogeneity and displayed a pl of 7.9 upon chromatofocusing. A monomeric molecular weight of 56,000 was obtained. The purified enzyme reacted with morphine but not with 4-hydroxybiphenyl, p-nitrophenol, testosterone, androsterone, estrone, bilirubin, 4-aminobiphenyl, or alpha-naphthylamine. The MgCl2 requirement for maximal expression of morphine glucuronidation was higher for the purified enzyme than for solubilized and intact microsomes. Codeine competitively inhibits morphine glucuronidation with an apparent Ki of 1.1 mM with the purified morphine UDPGT. 4-Hydroxybiphenyl UDPGT was separated from morphine UDPGT using a chromatofocusing procedure for Emulgen 911-solubilized microsomes. An apparent pl value of 5.5 was obtained for this protein. Based on this work we conclude that morphine and 4-hydroxybiphenyl can react with separate UDPGT isoforms.

Animals↗
PubMed1991

[Antigenic polysaccharides of Shigella bacteria. Structure of the polysaccharide chain of the lipopolysaccharide from Shigella boydii, type 11].

On mild acid degradation of the Shigella boydii, type 11 lipopolysaccharide, the corresponding O-specific polysaccharide composed of D-glucuronic acid, 2-acetylamino-2-deoxy-D-glucose, D-ribose and L-rhamnose residues in the ratio 1:1:1:3 was obtained. Methylation, partial acid hydrolysis and 13C-NMR spectral data for the polysaccharide led to the structure of the oligosaccharide repeating unit as a branched hexasaccharide: [formula: see text]. Numerous O-acetyl groups attached non-stoichiometrically to the residues of D-glucuronic acid, L-rhamnose and 2-acetylamino-2-deoxy-D-glucose were located with the use of 13C-NMR spectroscopy.

Antigens, Bacterial↗
PubMed1998

(4-O-Methyl-alpha-D-glucurono)-D-xylan from Rudbeckia fulgida, var. sullivantii (Boynton et Beadle).

From the medicinal plant Rudbeckia fulgida, var. sillivantii (Boynton et Beadle) a low-molecular-mass (4-O-methyl-alpha-D-glucurono)-D-xylan was isolated by alkaline extraction, followed by ethanol precipitation, ion-exchange chromatography and gel filtration. The results of compositional and linkage analyses, supported by those of 1H and 13C NMR measurements of oligomers generated on partial acid hydrolysis, showed the (1-->4)-linked beta-D-xylopyranosyl backbone with about 18% of 4-O-methyl-D-glucuronic acid attached to O-2 of the xylose residues. From the mean distance of adjacent carboxyl groups, obtained from experimentally determined single-ion activity coefficients of calcium counterions, it followed that the uronic acid units are separated and distributed regularly along the xylan chain, i.e. approximately each sixth D-xylose unit bears a 4-O-methyl-D-glucuronic acid residue.

Carbohydrate Sequence↗