Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GALACTOSE”

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 1,063 records · Page 59Linked to original sources
PubMed1994

Galactose consumption, metabolism, and follicle-stimulating hormone concentrations in women of late reproductive age.

OBJECTIVE: To test the hypothesis that high galactose consumption and low activity of galactose-1-phosphate uridyl transferase (transferase) is associated with early ovarian senescence among nongalactosemic women. DESIGN: Cross-sectional study. Data collection consisted of a self-administered questionnaire with sections on diet (food frequency data to measure galactose consumption), reproductive, and medical histories. One blood sample was collected to measure FSH and transferase activity; FSH was used as a measure of ovarian senescence. Among women who were having menstrual periods at least every 8 weeks, the blood sample was drawn in the early follicular phase (days 2 to 4) of a menstrual cycle. PARTICIPANTS: Two hundred ninety-five women volunteers ages 38 to 49 years who had not had a hysterectomy or oophorectomy were recruited through posters and advertisements. MAIN OUTCOME MEASURE: Serum FSH concentrations. RESULTS: Controlling for age, smoking, and body mass, transferase activity and FSH were unrelated. However, FSH levels were 29% higher (95% confidence intervals, 9% to 52%) among women who reported consuming > or = 6 g galactose/d. CONCLUSION: These data do not support the hypothesis that low transferase activity represents a genetic predisposition for early ovarian senescence, as measured by FSH levels in women ages 38 to 49 years. However, the hypothesized positive association between galactose consumption and FSH was supported.

Adult↗
PubMed1994

Binding of sugar ligands to Ca(2+)-dependent animal lectins. II. Generation of high-affinity galactose binding by site-directed mutagenesis.

Changes have been introduced into the Ca(2+)-dependent carbohydrate-recognition domain (CRD) of rat serum mannose-binding protein by site-directed mutagenesis to model the binding sites of homologous galactose-binding CRDs. Binding assays reveal that galactose-binding activity nearly identical to that of the CRD from the asialoglycoprotein receptor can be introduced into the mannose-binding site by 3 single amino acid changes and insertion of a segment of 5 amino acids. Separate changes are required to establish high-affinity binding to galactose and create high selectivity by exclusion of mannose from the binding site. The mutagenesis studies and NMR analysis of sugar-CRD titrations demonstrate that an important component of high-affinity galactose binding is interaction between the B face of the sugar and tryptophan. The binding properties of the C-type CRD from the cartilage proteoglycan, aggrecan, can also be modeled based on the mannose-binding CRD frame-work. This lower affinity binding site involves stacking of a phenylalanine residue against the sugar ligand.

Amino Acid Sequence↗
PubMed1993

[Prefeeding of aldose reductase inhibitor inhibits galactose cataract].

To examine the effect of prefeeding the aldose reductase inhibitor (ARI) on the cataract induced by the subsequent feeding of galactose diet, rats were first fed rat chow with or without ARI for 2 weeks. The animals were then transferred to a 25% galactose diet for different periods of time. Lenses were enucleated and examined by light microscopy. The amount of galactitol in the lenses was examined biochemically. The cataract was less severe and there was less galactitol in the lenses in the rats first fed with ARI than in those without ARI. These results indicate that the feeding the ARI prior to galactose feeding partly inhibits galactose cataract.

Aldehyde Reductase↗
PubMed1993

Effect of pregnancy on development of galactose-induced cataract in rat.

The effect of pregnancy on the development of galactose-induced cataract was studied in rats. Eight-week-old rats were fed a 50% galactose diet for 4 weeks. The rats were divided into three groups: nonpregnant females, pregnant females, and males. All eyes were examined by slit-lamp biomicroscope at 11 and 12 weeks of age, and the lenses were morphologically examined at 12 weeks. Clinically, the cataract showed a less advanced stage in the eyes of pregnant rats than in the eyes of the other two groups. Morphologically, the lenses of pregnant rats retained their normal structure. However, the lenses of the other two groups showed extensive damage. The plasma galactose levels and galactitol levels in lenses showed no significant difference among the three groups. Pregnancy was proved to inhibit the development of galactose cataract.

Animals↗
PubMed1993

Effect of galactose regimen on glomerular heparan sulfate synthesis and albumin excretion in diabetic rats.

Decreased glomerular heparan sulfate synthesis could account for the increased albuminuria observed in experimental diabetes. A similar albuminuria has been observed in galactose-fed animals. To test whether heparan sulfate synthesis is also decreased in galactosemic animals we measured the heparan sulfate synthesis in isolated renal glomeruli from streptozotocin diabetic and normal rats fed regular diets or 30% galactose diets for 11-12 weeks. Albumin excretion and glomerular heparan sulfate synthesis were determined at the time of sacrifice. As predicted by this hypothesis glomerular heparan sulfate synthesis was significantly lower in the diabetic group than in normals given regular diets (309 +/- 23 vs 487 +/- 56 dpm/mg glomerular wt.; P < 0.01), and albumin excretion greater in these diabetics than in the normals (20 +/- 4.3 vs 2.0 +/- 0.7 mg/24 hr; P < 0.002). Albumin excretion and glomerular heparan sulfate synthesis were also consistent with the hypothesis, but unpredictably reversed, in the galactose-fed diabetic group. Glomerular heparan sulfate synthesis was significantly increased in this group (713 +/- 67 dpm/mg glomerular wt.) and albumin excretion decreased (10.7 +/- 3.6 mg/24 hr) compared to the diabetic on regular diet. Some possible explanations are discussed, but the galactose effect described here remains phenomenological.

Albuminuria↗
PubMed1993

Experimental galactose neuropathy: quantitative changes in intramembranous particles in fracture faces of the perineurium.

Peripheral nerves in rats fed a diet containing 40% galactose develop endoneurial oedema related to the accumulation of interstitial galactitol and sodium. Biochemical studies of the perineurium in galactose neuropathy indicate an increase in membrane bound Na+/K(+)-ATPase activity. The present study has analysed the intramembraneous particles (IMPs) on the P membrane fracture faces of the perineurium in galactose-fed rats and has demonstrated a significant increase in the density of IMPs. This finding may reflect changes in the perineurial cell membranes in galactose neuropathy, such as increased membrane bound Na+/K(+)-ATPase activity.

Animals↗
PubMed1995

Vitamin B6 deficiency and galactose induced alterations in morphology and osmotic fragility of rat erythrocytes.

Recently, red blood cells have been investigated mainly for alterations in ion transporting capacity, membrane bound enzymes or modifications in the structure of its individual constituents in clinical and experimental urolithiasis. However, the implication of such modifications on the physical state or morphology of cells has not been investigated. Scanning electron microscopic studies performed in vitamin B6 deficient and/or galactose fed rat (established hyperoxaluric models) erythrocytes, showed the presence of large number of stomatocytes, spherocytes and other variously deformed cells as compared to discocytic cells seen in normal control group. These changes in shape were in concurrence with red cell osmotic fragility, which decreased both in vitamin B6 deficient and vitamin B6 deficient + galactose fed group (19 % and 33 % hemolysis at 4 g/l NaCl, respectively) while it increased in galactose control group (73 % hemolysis at 4 g/l NaCl) as compared to normal control group (55 % hemolysis at 4 g/l NaCl). These morphological and physical state alterations could be correlated with red blood cells' membrane cholesterol and phospholipid sub-class distribution. These findings suggest that some structural membrane changes occur due to vitamin B6 deficiency and/or galactose feeding, which may be responsible for the altered membrane functions known to be associated with pathogenesis of urolithiasis.

Animals↗
PubMed1976

The in vivo effect of colchicine on the addition of galactose and sialic acid to rat hepatic serum glycoproteins.

Colchicine inhibits the secretion of plasma protein by rat hepatocytes and causes their intracellular accumulation in Golgi-derived secretory vesicles. This study examines whether colchicine affects secretion before or after galactose and sialic acid have been added to the secretory glycoproteins. D-[G-3H] Galactose was injected into rats and was found to be incorporated into serum glycoproteins contained within Golgi-derived secretory vesicles. The administration of colchicine (25 mumol/100 g, body weight), immediately before the injection of D-[G-3H] galactose, caused an increase in radioactivity of the serum glycoproteins in these cell fractions. D-[G-3H] Glucosamine was incorporated into serum glycoproteins contained within the rough and smooth endoplasmic reticulum and the Golgi cell fractions; however, its incorporation into the sialic acid moieties of these proteins only occurred in Golgi-derived cell fractions. Colchicine administration resulted in an increased incorporation of D-[G-3H] glucosamine into the sialic acid residues of serum glycoproteins contained within the Golgi cell fractions. These data indicate that colchicine inhibits secretion of serum proteins by rat liver after the addition of galactose and sialic acid to the secretory proteins has taken place.

Animals↗
PubMed1996

High-resolution X-ray structure of UDP-galactose 4-epimerase complexed with UDP-phenol.

UDP-galactose 4-epimerase from Escherichia coli catalyzes the interconversion of UDP-glucose and UDP-galactose. In recent years, the enzyme has been the subject of intensive investigation due in part to its ability to facilitate nonstereospecific hydride transfer between beta-NADH and a 4-keto hexopyranose intermediate. The first molecular model of the epimerase from E. coli was solved to 2.5 A resolution with crystals grown in the presence of a substrate analogue, UDP-phenol (Bauer AJ, Rayment I, Frey PA, Holden HM, 1992, Proteins Struct Funct Genet 12:372-381). There were concerns at the time that the inhibitor did not adequately mimic the sugar moiety of a true substrate. Here we describe the high-resolution X-ray crystal structure of the ternary complex of UDP-galactose 4-epimerase with NADH and UDP-phenol. The model was refined to 1.8 A resolution with a final overall R-factor of 18.6%. This high-resolution structural analysis demonstrates that the original concerns were unfounded and that, in fact, UDP-phenol and UDP-glucose bind similarly. The carboxamide groups of the dinucleotides, in both subunits, are displaced significantly from the planes of the nicotinamide rings by hydrogen bonding interactions with Ser 124 and Tyr 149. UDP-galactose 4-epimerase belongs to a family of enzymes known as the short-chain dehydrogenases, which contain a characteristic Tyr-Lys couple thought to be important for catalysis. The epimerase/NADH/UDP-phenol model presented here represents a well-defined ternary complex for this family of proteins and, as such, provides important information regarding the possible role of the Tyr-Lys couple in the reaction mechanism.

20-Hydroxysteroid Dehydrogenases↗
PubMed1992

The molecular structure of UDP-galactose 4-epimerase from Escherichia coli determined at 2.5 A resolution.

UDP-galactose 4-epimerase catalyzes the conversion of UDP-galactose to UDP-glucose during normal galactose metabolism. The molecular structure of UDP-galactose 4-epimerase from Escherichia coli has now been solved to a nominal resolution of 2.5 A. As isolated from E. coli, the molecule is a dimer of chemically identical subunits with a total molecular weight of 79,000. Crystals of the enzyme used for this investigation were grown as a complex with the substrate analogue, UDP-benzene, and belonged to the space group P2(1)2(1)2(1) with unit cell dimensions of a = 76.3 A, b = 83.1 A, c = 132.1 A, and one dimer per asymmetric unit. An interpretable electron density map calculated to 2.5 A resolution was obtained by a combination of multiple isomorphous replacement with six heavy atom derivatives, molecular averaging, and solvent flattening. Each subunit of epimerase is divided into two domains. The larger N-terminal domain, composed of amino acid residues 1-180, shows a classic NAD+ binding motif with seven strands of parallel beta-pleated sheet flanked on either side of alpha-helices. The seventh strand of the beta-pleated sheet is contributed by amino acid residues from the smaller domain. In addition, this smaller C-terminal domain, consisting of amino acid residues 181-338, contains three strands of beta-pleated sheet, two major alpha-helices and one helical turn. The substrate analogue, UDP-benzene, binds in the cleft located between the two domains with its phenyl ring in close proximity to the nicotinamide ring of NAD+. Contrary to the extensive biochemical literature suggesting that epimerase binds only one NAD+ per functional dimer, the map clearly shows electron density for two nicotinamide cofactors binding in symmetry-related positions in the dimer. Likewise, each subunit in the dimer also binds one substrate analogue.

Computer Simulation↗
PubMed1995

Molecular cloning, characterization, and mapping of a full-length cDNA encoding human UDP-galactose 4'-epimerase.

Galactose metabolism in all organisms is catalyzed by three enzymatic steps: the galactokinase, galactose-1-phosphate uridyltransferase, and UDP galactose 4'-epimerase reactions. We report here the molecular cloning, characterization, and mapping of a full-length cDNA encoding human UDP-galactose 4'-epimerase (GALE). Our cDNA is 1488 bp long and matches the mRNA size of 1.5 kg detected in fibroblasts and lymphoblasts. The human GALE cDNA encodes a predicted protein of 348 amino acids with a molecular mass of 38,266. The human GALE enzyme is 87% identical to the rat protein, 53% identical to the homologous GAL10 protein from the yeast Kluyveromyces lactis, and 51% identical to the galE protein from the prokaryote Escherichia coli. This extraordinary degree of sequence identity has allowed us to build a homology model of the human protein based on the bacterial crystal structure. This predicted human structure is very similar to the E. coli galE enzyme, suggesting that both enzymes use similar mechanisms. The human gene encoding GALE maps, as expected, to a single locus on chromosome 1 and appears to be compact. The human GALE gene is structurally intact in 19 patients with epimerase-deficiency galactosemia, an inborn error of metabolism secondary to GALE deficiency. Therefore, we propose that this disorder is due to small mutations within the gene.

Amino Acid Sequence↗
PubMed1999

Recognition of Amphiphiles with Many Pendent Galactose Residues by Ricinus communis Agglutinin.

Amphiphiles which carry many pendent galactose residues as side chains were prepared by telomerization of 2-methacryloyloxyethyl beta-D-galactopyranoside (MEGal) or 3-(2-methacryloyl aminoethylthio)propyl D-galactopyranoside (MEPGal, alpha:beta = 3.9:1) using a lipophilic radical initiator. The galactose-carrying amphiphiles (DP (degree of polymerization) = 15) incorporated in liposomes were recognized by a lectin from Ricinus communis (RCA120), which was proven by the increase in turbidity of the liposome suspension after mixing with the lectin. The recognition was largely affected by the distance between the galactose residues and the polymer main chain, and the surface density of the amphiphile in the liposomes. The liposomes containing these galactolipids were not taken up by mouse peritoneal macrophages, probably due to a steric hindrance of polymer main chains from the uptake of D-galactose receptors on the macrophages. Copyright 1999 Academic Press.

Journal Article↗
PubMed1981

Reversion from deficiency of galactose-1-phosphate uridylytransferase (GALT) in an SV40-transformed human fibroblast line.

Control SV40-transformed human fibroblasts can be readily adapted to growth on medium containing galactose as sole hexose source (galactose-MEH). However, most cells from a line of SV40-transformed skin fibroblasts from a patient with galactosemia (galactose-1-phosphate uridylyltransferase (GALT) deficiency) died in galactose-MEM. Surviving cells of this line either grew in completely sugar-free media or had acquired significant amounts of GALT activity. Two presumptive revertant cell lines with GALT activity were characterized in detail. The expression of GALT in these two lines was stable in nonselective conditions. Each had different reaction maximum velocities with respect to uridine diphosphoglucose (UDPg) concentration as compared to residual activity in the parental cell strain or control cells. Both appeared to demonstrate heat-inactivation profiles for GALT than differed from the parental cells or controls. UDPG concentration was found to significantly alter the thermostability of GALT. A competitive radioimmunoassay for GALT showed that these two lines had amounts of the GALT protein comparable to that of the parental cell strain or control cells. The electrophoretic mobility of GALT from the two presumptive revertants was found to differ from control cells. It was concluded that structural gene changes were probably responsible for the apparent reversion in these lines.

Cell Line↗
PubMed1975

Zero-trans and equilibrium-exchange efflux and infinite-trans uptake of galactose by human erythrocytes.

1. The zero-trans and equilibrium exchange efflux and the infinite-trans uptake of galactose in human erythrocytes were measured as a function of galactose concentration at 20 %. 2. The zero-trans procedure with cells loaded with 285 mM galactose revealed a low affinity site for galactose transport at the inner face of the membrane having a maximal velocity of 255 plus or minus 96 mmol/l isotonic cell water and Km equals 240 plus or minus 57, the V/K ratio being 1.01 plus or minus 0.04 min-1. 3. The equibirum-exchange procedure yielded a maximal velocity of 432 plus or minus 44 mmol/cell unit per min and K equals 138 plus or minus 57, the V/K ratio being3.19 plus or minus 0.52 min-1. 4. The infinite-trans uptake revealed a high affinity site at the outer face of the membrane having a maximal velocity of 239 plus or minus 11 mmol/cell unit per min, and K equals 21 plus or minus 2 mM. 5. These results combined with previous findings (Ginsburg, H. and Stein, W. D. (1975) Biochim. Biophys. Acta 000, 000-000) force us to reject the following models for sugar transport in human erythrocytes: a single asymmetric carrier; two symmetric carriers in parallel, the original form of the internal transfer model.

Biological Transport, Active↗
PubMed1990

The N-linked carbohydrate chain of the 85-kilodalton glycoprotein from Trypanosoma cruzi trypomastigotes contains sialyl, fucosyl and galactosyl (alpha 1-3)galactose units.

The structure of the N-linked oligosaccharide of the 85-kDa surface glycoprotein (Tc-85) from the infective trypomastigote form of Trypanosoma cruzi was investigated. Tc-85 metabolically labeled with [14C]glucose was purified by affinity chromatography on wheat germ agglutinin-Sepharose. Binding to the lectin was lost on treatment of Tc-85 with neuraminidase. The N-linked asialo-oligosaccharide was released by endo-beta-N-acetylglucosaminidase F digestion of asialo-Tc-85 and was further analyzed using specific exoglycosidases. [14C]fucose was detected after alpha-L-fucosidase treatment or mild acid hydrolysis. The afucosyl oligosaccharide was 3H-labeled by the galactose oxidase-NaB3H4 method. [3H]Galactose was released by alpha-galactosidase, and only then was beta-galactosidase effective in removing another galactose. The gal(alpha 1-3)gal unit was demonstrated by periodate oxidation studies on the [3H]galactose-labeled asialo-glycoprotein. The presence of gal(alpha 1-3)gal in Tc-85 could be related to the recent finding of elevated antibody levels against this epitope in patients with Chagas' disease.

Acetylglucosaminidase↗
PubMed1991

Dynamics of activation of a galactose-inducible promoter in Saccharomyces cerevisiae.

We have investigated the dynamics of accumulation of the Escherichia coli beta-galactosidase (beta-gal) under the control of a promoter containing the galactose-inducible upstream activating sequence (UASG) in single Saccharomyces cerevisiae cells. The accumulation of beta-gal in single cells following the addition of the inducer, galactose, was determined using an in situ combined DNA and immunofluorescent stain in conjunction with flow cytometry. Two strains were studied, D603/2i, which has two copies of the galactose-inducible fusion gene integrated into its genome, and D603/pLGSD5, which carries a 2 microns-based plasmid containing the fusion gene. Flow cytometry results indicate that accumulation of beta-gal within the first three hours following the addition of galactose is dependent on cell cycle position. Two proposed mechanisms explaining this observed behavior are (1) the cell-cycle-dependent synthesis of the fusion protein or (2) the unequal partitioning of the protein at cell division between mother and daughter cells.

Cell Cycle↗
PubMed1985

Aldose reductase, NADPH and NADP+ in normal, galactose-fed and diabetic rat lens.

NADPH and NADP+ levels were measured in rat lens from normal controls, from galactose-fed and diabetic rats during the first week of cataract formation. The level of NADPH in normal rat lens was determined to be 12.3 +/- 0.4 nmol/g wet weight, and that of NADP+ 4.6 +/- 0.2 nmol/g wet weight. In early cataract formation NADPH levels decreased rapidly during the first 2 days and then remained stable at 76% of control for galactose-fed and 84% for diabetic rats. NADP+ levels increased by 38% of control for galactose-fed and 54% for diabetic rats. Calculated NADPH/NADP+ ratios dropped from 3.36 +/- 0.21 to 1.86 +/- 0.16 in galactose fed rats, and from 2.81 +/- 0.15 to 1.61 +/- 0.16 in diabetic rats (P less than 0.001 for both experimental groups). These data are consistent with rapid NADPH oxidation during onset of lens cataracts. No significant changes in aldose reductase enzymatic activity levels were observed in either the galactosemic or the diabetic rats during the times measured.

Aldehyde Reductase↗
PubMed1984

Plasmid vectors for positive galactose-resistance selection of cloned DNA in Escherichia coli.

Insertion of a HindIII-EcoRI fragment carrying part of the gal operon from lambda gal+ into pBR322 yields a plasmid (pAA3) which confers strong galactose sensitivity on E. coli strains deleted for the gal operon. Sensitivity to galactose is caused by the expression of kinase and transferase (but not epimerase) genes from a promoter located in the tet gene of pBR322. Insertion of a DNA fragment carrying Tn9 at the HindIII junction blocks gal expression and produces a galactose-resistant phenotype. Hence, galactose resistance can be used to select DNA fragments cloned at the HindIII site. The system was used efficiently for cloning lambda, yeast, and human DNA. The cloned fragments can be screened directly for the presence of promoters by testing for tetracycline resistance. Alternatively, these plasmids can be used as cosmids for cloning large fragments of DNA at a number of sites. Construction of several related vectors is described.

Bacterial Proteins↗