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.

SourceResearch connectionFrom yearThrough year

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

At least 145 records · Page 8Linked to original sources

PubMed1976

Modifications of drug metabolism by disulfiram and diethyldithiocarbamate. II. D-Glucuronic acid pathway.

Hepatic enzymes connected with the formation and metabolism of free D-glucuronic acid were affected in rats after treatment with disulfiram or diethyldithiocarbamate (300 mg/kg, intragastrically, per day, 4 X). The activities of UDPglucose dehydrogenase, UDPglucuronic acid pyrophosphatase, UDPglucuronosyltransferase and L-gulonate dehydrogenase were enhanced, while those of glucose-6-phosphate dehydrogenase, beta-glucuronidase and D-glucuronolactone dehydrogenase were inhibited. These changes were more pronounced with disulfiram than diethyldithiocarbamate. Treatment with phenobarbital (80 mg/kg, i.p., per day, 4 X) enhanced UDP glucuronosyl-transferase, but brought about different effects on the other enzymes. Concurrent administration of phenobarbital with disulfiram or diethyldithiocarbamate led to potentiation or antagonism of the primary effects of each compound when given alone. The results suggest that activation of the D-glucuronic acid pathway may proceed in various ways, and that it is not necessarily followed by a simultaneous induction of the microsomal mixed-function oxygenase activity.

Alcohol Oxidoreductases↗

PubMed2002

Conversion of glucuronic acid glycosides to novel bicyclic beta-lactams.

[reaction: see text] Methodology for the conversion of glucuronic acid glycosides to novel bicyclic beta-lactams is reported. Using this strategy, we prepared two novel templates suitable for use in combinatorial chemistry strategies for the construction of a number of interesting beta-lactam motifs. Key features of this strategy include a diastereoselective Ferrier reaction of a glucuronic acid glucal, selective beta-lactam ring formation using a cyclic allylic alcohol, and a chemoselective benzylic oxidation.

Combinatorial Chemistry Techniques↗

PubMed1976

An extracellular fungal polysaccharide composed of 2-acetamido-2-deoxy-D-glucuronic acid residues.

The black yeast-like fungus NRRL YB-4163, now tentatively identified as Rhinocladiella elatior Mangenot, has been found to produce an extracellular microbial polysaccharide composed mainly of 2-acetamido-2-deoxy-D-glucuronic acid residues. Polysaccharide (PS) YB-4163, when isolated in good yield as the neutral potassium salt, dissolves readily in water to produce extremely viscous solutions, which form stable foams and emulsions. By depolymerizing PS YB-4163 with [14C]methanol-HCl, the polysaccharide can be both identified and quantitated radiochemically by determining the individual [14C]methyl glycosides after their separation by paper chromatography. When the methyl glycosides of PS YB-4163 were reduced with NaB3H4, only the methyl glycosides of 2-acetamido-2-deoxy-D-[6-3H]glucose were found. Analysis of the monosaccharide released from carboxyl-reduced PS YB-4163 by acid hydrolysis or methanolysis also showed 2-acetamido-2-deoxy-D-glucuronic acid to be the main constituent. Previously, the only polysaccharides known to be composed entirely or hexosaminuronic acid have been cellular products from pathogens. Of these, the antigenic polysaccharide (SPSA) from Staphylococcus aureus is composed entirely of 2-amino-2-deoxy-D-glucuronic acid, but its amino groups are substituted equally with acetyl and N-acetylalanyl groups. The specific optical rotation of PS YB-4163, [alpha]20D -75 degrees (c 0.5, water), is similar to that of SPSA (-91 degrees), and suggests beta-D-linkages that must be either (1 leads to 3) or (1 leads to 4).

Glucuronates↗

PubMed1978

Isolation of a novel sphingoglycolipid containing glucuronic acid and 2-hydroxy fatty acid from Flavobacterium devorans ATCC 10829.

A new acidic sphingoglycolipid has been isolated from a Gram-negative, glucose-non-fermentative (obligatory aerobic) bacterium, Flavobacterium devorans ATCC 10829, by thin-layer chromatography on silica gel after mild alkaline hydrolysis of the cellular lipids. Chemical degradation studies, thin-layer chromatographic behavior, IR and mass-spectrometric analysis of the original and reduced glycolipid with LiA1H4 revealed that the lipid contained glucuronic acid, long-chain bases, and fatty acids in a molar ratio of approximately 1:1:1. The major long-chain bases were identified by gas chromatography-mass spectrometry as dihydrosphingosine (d-18 :0) and longer homologues, while the N-acyl group was exclusively 2-hydroxy myristic acid. The most probable structure of this glycolipid appeared to be a ceramide glucuronic acid (N-acyl dihydrosphingosine 1-glucuronic acid).

Flavobacterium↗

PubMed1970

Control of uridine diphosphate-glucose dehydrogenase synthesis and uridine diphosphate-glucuronic acid accumulation by a regulator gene mutation in Escherichia coli K-12.

Uridine diphosphate (UDP)-glucose dehydrogenase, the enzyme that converts UDP-glucose to UDP-glucuronic acid, was derepressed in a mucoid (capR9) strain of Escherichia coli K-12 and repressed in a nonmucoid (capR(+)) strain. A nonmucoid mutant (strain MC 152; capR9 non-2) derived from the mucoid strain accumulated large quantities of nucleotides. Among these nucleotides, UDP-glucuronic acid was identified as well as guanosine triphosphate and an adenosine diphosphate-sugar. UDP-glucose dehydrogenase was still derepressed in strain MC 152. When the nonmucoid mutant was transduced to the wild-type state for this regulator gene (capR(+)), the transductant was found to accumulate less total nucleotides, and the accumulation of UDP-glucuronic acid was abolished. UDP-glucose dehydrogenase was repressed in the capR(+)non-2 strain but not to the same extent that it was in the capR(+) strain.

Alcohol Oxidoreductases↗

PubMed1994

Determination of the HNK-1 epitope (3-sulphated glucuronic acid) in intact chondroitin sulphates by ELISA. Application to squid skin proteoglycans and their oversulphated carbohydrate structures.

The reactivity of the HNK-1 monoclonal antibody to chondroitin sulphates and derived disaccharides was studied using an ELISA inhibition test. The antibody readily reacted with its specific epitope (3-sulphated glucuronic acid) in intact chondroitin sulphates as well as with the equivalent oversulphated delta 4-disaccharides obtained by chondroitinase digestion and identified as sulphated at C-3 of the hexuronate. It is showed that by using the oversulphated delta 4-disaccharides as standards in an ELISA inhibition test, the amount of 3-sulphated glucuronic acid can be estimated also in the polymer preparations. When applying this ELISA test to the PG populations isolated from squid skin, most of the oversulphation seen in HPLC analyses of these preparations was found to be associated with 3-sulphation of the glucuronic acid.

Animals↗

PubMed2004

The biosynthesis of UDP-galacturonic acid in plants. Functional cloning and characterization of Arabidopsis UDP-D-glucuronic acid 4-epimerase.

UDP-GlcA 4-epimerase (UGlcAE) catalyzes the epimerization of UDP-alpha-D-glucuronic acid (UDP-GlcA) to UDP-alpha-D-galacturonic acid (UDP-GalA). UDP-GalA is a precursor for the synthesis of numerous cell-surface polysaccharides in bacteria and plants. Using a biochemical screen, a gene encoding AtUGlcAE1 in Arabidopsis (Arabidopsis thaliana) was identified and the recombinant enzyme biochemically characterized. The gene belongs to a small gene family composed of six isoforms. All members of the UGlcAE gene family encode a putative type-II membrane protein and have two domains: a variable N-terminal region approximately 120 amino acids long composed of a predicted cytosolic, transmembrane, and stem domain, followed by a large conserved C-terminal catalytic region approximately 300 amino acids long composed of a highly conserved catalytic domain found in a large protein family of epimerase/dehydratases. The recombinant epimerase has a predicted molecular mass of approximately 43 kD, although size-exclusion chromatography suggests that it may exist as a dimer (approximately 88 kD). AtUGlcAE1 forms UDP-GalA with an equilibrium constant value of approximately 1.9 and has an apparent K(m) value of 720 microm for UDP-GlcA. The enzyme has maximum activity at pH 7.5 and is active between 20 degrees C and 55 degrees C. Arabidopsis AtUGlcAE1 is not inhibited by UDP-Glc, UDP-Gal, or UMP. However, the enzyme is inhibited by UDP-Xyl and UDP-Ara, suggesting that these nucleotide sugars have a role in regulating the synthesis of pectin. The cloning of the AtUGlcAE1 gene will increase our ability to investigate the molecular factors that regulate pectin biosynthesis in plants. The availability of a functional recombinant UDP-GlcA 4-epimerase will be of considerable value for the facile generation of UDP-d-GalA in the amounts required for detailed studies of pectin biosynthesis.

Amino Acid Sequence↗

PubMed1974

myo-Inositol 1-Phosphate Synthase Inhibition and Control of Uridine Diphosphate-d-glucuronic Acid Biosynthesis in Plants.

Of the eight intermediates associated with the two pathways of UDP-d-glucuronic acid biosynthesis found in plants, only d-glucuronic acid inhibited myo-inositol 1-phosphate synthase (EC 5.5.1.4), formerly referred to as d-glucose 6-phosphate cycloaldolase. Inhibition was competitive. An attempt to demonstrate over-all reversibility of the synthase indicated that it was less than 5% reversible, if at all.

Journal Article↗

PubMed1987

Determination of the distribution of D-glucuronic acid units within the chain of pig-skin dermatan sulfate near the linkage region.

A method for analyzing the distribution of D-glucuronic acid units within the chain and near the linkage region of dermatan sulfate has been developed. The method consists of a chemical modification of the reducing terminal residue in the polysaccharide by reductive amination with excess 1,2-diaminoethane in the presence of sodium cyanoborohydride, desulfative fragmentation of the polysaccharide, labeled with 2-aminoethylamino (AEA) groups, in hot dimethyl sulfoxide containing 10% of water followed by 2,4-dinitrophenylation of the 2-aminoethylamino group, separation of the 2-(2,4-dinitrophenylamino)ethylamino labeled dermatan fragments from nonlabeled fragments on Octyl-Sepharose CL-4B gel, and determination of the uronic acid composition of the labeled fragments having various chain-length. A preparation of pig-skin dermatan sulfate (Mr 21,000, ratio of GlcA to total uronic acid, 93:500) showed an average distribution pattern of D-glucuronic acid residues near the linkage region of one N-acetylchondrosine unit in the disaccharide sequence 1-5(6) linked to the Xyl----Gal----Gal----GlcA residue, a cluster of 6-8 N-acetyldermosine units in the sequence 6(7)-12(13), and four separate N-acetylchondrosine units between the sequence adjacent to the N-acetyldermosine cluster and the sequence 23 or higher.

Animals↗

PubMed1993

[Mechanisms of the stimulating effect of d-glucuronic acid on the processes of bone marrow granulomonocytopoiesis in cytostatic myelodepression].

The mechanisms of regulating influence of D-glucuronic acid on granulomonocytopoiesis++ have been studied by using the model of cyclophosphamide-induced myelodepression. Increase of colony-stimulating and interleukin-1 activities production by hemopoiesis inducing microenvironment cells, the stimulation of hemopoietic islets and the different granulomonocytopoiesis precursor cells forming have been shown to be the base of activating action of D-glucuronic acid on bone marrow granulomonocytopoiesis recovery.

Animals↗

PubMed2006

Phylogenetic and mutational analyses reveal key residues for UDP-glucuronic acid binding and activity of beta1,3-glucuronosyltransferase I (GlcAT-I).

The beta1,3-glucuronosyltransferases are responsible for the completion of the protein-glycosaminoglycan linkage region of proteoglycans and of the HNK1 epitope of glycoproteins and glycolipids by transferring glucuronic acid from UDP-alpha-D-glucuronic acid (UDP-GlcA) onto a terminal galactose residue. Here, we develop phylogenetic and mutational approaches to identify critical residues involved in UDP-GlcA binding and enzyme activity of the human beta1,3-glucuronosyltransferase I (GlcAT-I), which plays a key role in glycosaminoglycan biosynthesis. Phylogeny analysis identified 119 related beta1,3-glucuronosyltransferase sequences in vertebrates, invertebrates, and plants that contain eight conserved peptide motifs with 15 highly conserved amino acids. Sequence homology and structural information suggest that Y84, D113, R156, R161, and R310 residues belong to the UDP-GlcA binding site. The importance of these residues is assessed by site-directed mutagenesis, UDP affinity and kinetic analyses. Our data show that uridine binding is primarily governed by stacking interactions with the phenyl group of Y84 and also involves interactions with aspartate 113. Furthermore, we found that R156 is critical for enzyme activity but not for UDP binding, whereas R310 appears less important with regard to both activity and UDP interactions. These results clearly discriminate the function of these two active site residues that were predicted to interact with the pyrophosphate group of UDP-GlcA. Finally, mutation of R161 severely compromises GlcAT-I activity, emphasizing the major contribution of this invariant residue. Altogether, this phylogenetic approach sustained by biochemical analyses affords new insight into the organization of the beta1,3-glucuronosyltransferase family and distinguishes the respective importance of conserved residues in UDP-GlcA binding and activity of GlcAT-I.

Amino Acids↗

PubMed1980

Enterohepatic recycling of phenolphthalein, morphine, lysergic acid diethylamide (LSD) and diphenylacetic acid in the rat. Hydrolysis of glucuronic acid conjugates in the gut lumen.

1. Biliary elimination in female Wistar albino rats 3 h after i.p. injection of [3H]phenolphthalein, [3H]morphine, 14C-LSD and [14C]diphenylacetic acid was 90%, 45%, 75% and 57% respectively, predominantly as glucuronides. 2. Infusion of 3 h bile from the previous experiments into the duodena of bile-duct-cannulated animals demonstrated enterohepatic circulation, amounting in 24 h to 85%, 41%, 28% and 66% of the infused doses of the conjugates of phenolphthalein, morphine, LSD and diphenylacetic acid respectively. 3. Pretreatment with antibiotics to suppress intestinal microflora decreased this enterohepatic recirculation to 22%, 8.6% and 21% in 24 h for phenolphthalein, morphine and diphenylacetic acid glucuronides respectively. Antibiotic pretreatment did not influence the absorption and re-excretion of infused doses of the free aglycones, thus demonstrating the importance of bacterial beta-glucuronidase hydrolysis of the biliary conjugates. 4. The extent of intestinal absorption of the aglycones after bacterial beta-glucuronidase hydrolysis of the conjugates is related to their lipid-solubility as estimated by octan-1-ol:0.1 M phosphate buffer partition ratios (P-values). 5. The persistence of compounds in the enterohepatic circulation is determined by the faecal and urinary elimination of the circulating compounds. Faecal elimination is governed by the extent of intestinal absorption of the circulating compounds, which is influenced by the efficacy of intestinal hydrolysis of the conjugates and the relative lipophilicity of the aglycones released.

Animals↗

PubMed1995

Conformational analysis of segments of oxidized cellulose. Part I: Molecular modelling of glucuronic acid dimers considering the effect of counter-ions and a polar environment.

Conformational analysis of various forms of glucuronic acid dimers as the model structures of oxidized cellulose has been performed using molecular mechanics with a CVFF force field. The effects of ionization of carboxyl groups, ion pairing with explicit consideration of counter-ions (Na+, Mg2+) and the implicit inclusion of a solvent effect via the dielectric constant, epsilon, have been simulated. The non-ionized glucuronic acid dimer shows conformational behaviour similar to that of unoxidized cellobiose. The ionization of COOH groups leads to strong destabilization of C and D conformers (with both COO- groups on the same side of the molecule), while complexation with counter-ions leads to strong stabilization of these forms which yield highly wound low-pitch helices. An increase in the solvent polarity has an attenuating effect on the behaviour described above.

Anions↗

PubMed2002

Enzymatic synthesis of chondroitin with a novel chondroitin sulfate N-acetylgalactosaminyltransferase that transfers N-acetylgalactosamine to glucuronic acid in initiation and elongation of chondroitin sulfate synthesis.

We found a novel glycosyltransferase gene having a hypothetical beta 1,4-galactosyltransferase motif (GenBank accession number ) by a BLAST search and cloned its full-length open reading frame using the 5'-rapid amplification of cDNA ends method. The truncated form was expressed in insect cells as a soluble enzyme. It transferred N-acetylgalactosamine, not galactose, to para-nitrophenyl-beta-glucuronic acid. The N-acetylgalactosamine-glucuronic acid linkage has been identified only in chondroitin sulfate; therefore, we examined its chondroitin elongation and initiation activities. N-Acetylgalactosaminyltransferase activity was observed toward chondroitin poly- and oligosaccharides, chondroitin sulfate oligosaccharides, and linkage tetrasaccharide (GlcA-Gal-Gal-Xyl-O-methoxyphenyl), and the chondroitin polysaccharide and linkage tetrasaccharide were better acceptor substrates than the others. Northern blot analysis and quantitative real-time PCR analysis revealed that its 4-kb transcripts were highly expressed in thyroid and placenta, although they were ubiquitously expressed in various tissues and cells. These results suggest that this enzyme has N-acetylgalactosaminyltransferase activity in both the elongation and initiation of chondroitin sulfate synthesis. Furthermore, we performed enzymatic synthesis of chondroitin pentasaccharide in vitro. In one tube reaction with four enzymes, beta 1,4-galactosyltransferase-VII, beta 1,3-galactosyltransferase-VI, glucuronyltransferase-I, and this enzyme, and a synthetic xylose-peptide acceptor, the structure GalNAc-GlcA-Gal-Gal-Xyl-peptide was constructed. This is the first report of a chondroitin pentasaccharide constructed with recombinant glycosyltransferases in vitro.

Acetylgalactosamine↗

PubMed1980

Structural studies on heparan sulphate from human lung fibroblasts. Characterization of oligosaccharides obtained by selective periodate oxidation of D-glucuronic acid residues followed by scission in alkali.

1. (3)H- and (35)S-labelled heparan sulphate was isolated from monolayers of human lung fibroblasts and subjected to degradations by (a) deaminative cleavage and (b) periodate oxidation/alkaline elimination. Fragments were resolved by gel- and ion-exchange-chromatography. 2. Deaminative cleavage of the radioactive glycan afforded mainly disaccharides with a low content of ester-sulphate and free sulphate, indicating that a large part (approx. 80%) of the repeating units consisted of uronosyl-glucosamine-N-sulphate. Blocks of non-sulphated [glucuronosyl-N-acetyl glucosamine] repeats (3-4 consecutive units) accounted for the remainder of the chains. 3. By selective oxidation of glucuronic acid residues associated with N-acetylglucosamine, followed by scission in alkali, the radioactive glycan was degraded into a series of fragments. The glucuronosyl-N-acetylglucosamine-containing block regions yielded a compound N-acetylglucosamine-R, where R is the remnant of an oxidized and degraded glucuronic acid. Periodate-insensitive uronic acid residues were recovered in saccharides of the general structure glucosamine-(uronic acid-glucosamine)(n)-R. 4. Further degradations of these saccharides via deaminative cleavage and re-oxidations with periodate revealed that iduronic acid may be located in sequences such as glucosamine-N-sulphate-->iduronic acid-->N-acetylglucosamine. Occasionally the iduronic acid was sulphated. Blocks of iduronic acid-containing repeats may contain up to five consecutive units. Alternating arrangements of iduronic acid- and glucuronic acid-containing repeats were also observed. 5. (3)H- and (35)S-labelled heparan sulphates from sequential extracts of fibroblasts (medium, EDTA, trypsin digest, dithiothreitol extract, cell-soluble and cell-insoluble material) afforded similar profiles after both periodate oxidation/alkaline elimination and deaminative cleavage.

Alkalies↗

PubMed1996

Two kinetically-distinct components of UDP-glucuronic acid transport in rat liver endoplasmic reticulum.

Previous studies have documented the presence of protein-mediated transport of UDP-glucuronic acid (UDP-GlcUA) in rat liver endoplasmic reticulum (ER). Measurement of uptake at varying concentrations of high specific activity [beta-32P]UDP-GlcUA has revealed the presence of a two component UDP-GlcUA transporting system. Transport at low substrate concentrations occurred predominantly via a high affinity component (K(m) = 1.6 microM), whereas a low affinity component (K(m) = 38 microM) predominated at high substrate concentrations. The K(m) for the high affinity system is in agreement with that previously published, while the low affinity component is a new finding. The uptake of UDP-GlcUA was temperature-sensitive, time dependent, and saturable for both components. The high affinity transport was affected by trans-stimulation and cis-inhibition by UDP-N-acetylglucosamine (UDP-GlcNAc); however, the same concentrations of UDP-GlcNAc had less effect on the low affinity system. In order to further study the two transport components, various inhibitors of anion transport carriers were tested. The high affinity component was strongly inhibited by 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and furosemide, while the low affinity system was less sensitive to these reagents. Dose-dependent inhibition by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) was found for both transport systems. Probenecid was found to be a weak inhibitor of both components of the UDP-GlcUA uptake. Finally, the major metabolite of 3'-azido-3'-deoxythymidine, 3'-azido-3'-deoxythymidine monophosphate (AZTMP), was able to inhibit the uptake of UDP-GlcUA by both components. The results indicate the presence of two carrier-mediated UDP-glucuronic acid transporting components in rat liver ER.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

PubMed2001

Oxidative decarboxylation of UDP-glucuronic acid in extracts of polymyxin-resistant Escherichia coli. Origin of lipid a species modified with 4-amino-4-deoxy-L-arabinose.

Addition of the 4-amino-4-deoxy-l-arabinose (l-Ara4N) moiety to the phosphate groups of lipid A is implicated in bacterial resistance to polymyxin and cationic antimicrobial peptides of the innate immune system. The sequences of the products of the Salmonella typhimurium pmrE and pmrF loci, both of which are required for polymyxin resistance, recently led us to propose a pathway for l-Ara4N biosynthesis from UDP-glucuronic acid (Zhou, Z., Lin, S., Cotter, R. J., and Raetz, C. R. H. (1999) J. Biol. Chem. 274, 18503-18514). We now report that extracts of a polymyxin-resistant mutant of Escherichia coli catalyze the C-4" oxidation and C-6" decarboxylation of [alpha-(32)P]UDP-glucuronic acid, followed by transamination to generate [alpha-(32)P]UDP-l-Ara4N, when NAD and glutamate are added as co-substrates. In addition, the [alpha-(32)P]UDP-l-Ara4N is formylated when N-10-formyltetrahydrofolate is included. These activities are consistent with the proposed functions of two of the gene products (PmrI and PmrH) of the pmrF operon. PmrI (renamed ArnA) was overexpressed using a T7 construct, and shown by itself to catalyze the unprecedented oxidative decarboxylation of UDP-glucuronic acid to form uridine 5'-(beta-l-threo-pentapyranosyl-4"-ulose diphosphate). A 6-mg sample of the latter was purified, and its structure was validated by NMR studies as the hydrate of the 4" ketone. ArnA resembles UDP-galactose epimerase, dTDP-glucose-4,6-dehydratase, and UDP-xylose synthase in oxidizing the C-4" position of its substrate, but differs in that it releases the NADH product.

Amino Sugars↗

PubMed2003

Synthesis of the trisaccharide portion of soyasaponin beta g: evaluation of a new glucuronic acid acceptor.

The synthesis of the trisaccharide portion of soyasaponin beta g was successfully achieved using a new glucuronic acid acceptor: methyl 1-O-allyl-3,4-di-O-methoxymethyl-beta-D-glucuronate (9). This compound and methyl 1-O-allyl-3,4-di-O-tert-butyldimethylsilyl-beta-D-glucuronate (8) were both prepared from glucuronolactone via a glycal intermediate. The former compound 9 was successfully coupled to ethyl 2-O-benzoyl-3,4,6-tri-O-benzyl-1-thio-beta-D-galactopyranoside (13) in excellent yield. Synthesis of the protected trisaccharide was then completed by the addition of a suitably protected rhamnose derivative to the disaccharide portion. The reactivity of the glucuronic acid derivative 9 was also explored with trichloroacetimidate and fluoride donors.

Carbohydrate Sequence↗