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 487 records · Page 27Linked to original sources
PubMed2000

Retinal capillary dilation: early diabetic-like retinopathy in the galactose-fed rat model.

UNLABELLED: The purpose of this study was to determine whether capillary dilation is one of the earliest structural changes in the diabetic-like retinopathy of the galactose-fed rat model and thus may represent a stage where intervention treatment might still be effective. Weanling female Sprague-Dawley rats were randomized into 3 groups and fed Purina laboratory chow plus one of the following for 4 months: 50% starch (CONTROL); 50% D-galactose (Galactose); or 50% D-galactose with ARI-509 (25 mg/kg body wt/day) (Inhibitor). One eye from each of 5 rats per treatment group was processed for retinal vasculature wholemounts using elastase digestion, stained with a standard periodic-acid-Schiff reaction and counterstained with hematoxylin. Average capillary width, overall capillary density and total capillary length were measured, using computerized image analysis, within an arc-shaped area (4.4 mm2) of each vasculature surrounding, but separated from, the optic disc margin by approximately 0.7 mm. Galactose rats exhibited significant (p < 0.001) increases in capillary width (Mean +/- SEM: 7.56 +/- 0.07 microm) and density (42.78 +/- 0.37%) compared with CONTROL rats (6.68 +/- 0.11 microm and 37.18 +/- 0.30%, respectively). These increases were prevented with inhibitor treatment (6.58 +/- 0.16 microm and 35.88 +/- 0.97%, respectively). Capillary length remained unchanged at 4 months ( CONTROL: 246.66 +/- 2.46 mm; Galactose: 250.75 +/- 1.26 mm; Inhibitor: 242.25 +/- 8.43 mm). Retinal capillary dilation, expressed as increased width and density, is one of the earliest detectable lesions in galactose-fed rats. In these rats, the lesion occurs as early as retinal capillary basement membrane thickening (RCBMT), one of the earliest reported changes in human diabetic retinopathy. Like RCBMT, capillary dilation can be prevented in rats with aldose reductase inhibitor treatment. Unlike RCBMT, capillary dilation could be clinically detectable and may be useful for the diagnosis of early retinopathy and for determining the timing of therapeutic intervention.

Aldehyde Reductase↗
PubMed1981

IMP1/imp1: a gene involved in the nucleo-mitochondrial control of galactose fermentation in Saccharomyces cerevisiae.

In some strains of Saccharomyces cerevisiae, the induction of enzymes of the Leloir pathway, galactose fermentation and growth on galactose depend on mitochondrial function; mitochondrial dependence is elicited through the recessive allele imp1 of the nuclear gene IMP1. The genetic element IMP1 is not allelic to any of the known GAL genes; IMP1 strains can grow on and ferment galactose in respiratory-deficient (RD) condition or in the presence of the mitochondrial inhibitors ethidium bromide and erythromycin; whereas, imp1 strains can grow on and ferment galactose only in respiratory-sufficient (RS) condition. The imp1 elicited mitochondrial dependence apparently involves regulation of the synthesis of the galactose catabolizing enzymes and synthesis of the galactose specific permease. IMP1 is not the only genetic determinant that elicits an interaction of the mitochondrion and the expression of the Gal system; the GAL3 gene, whose role in galactose utilization is demonstrated by the long-term adaptation phenotype of gal3 rS mutants, gives rise to a noninducible phenotype in RD condition or in the presence of mitochondrial inhibitors.

Cell Nucleus↗
PubMed2003

Galactose toxicity in the rat as a model for premature ovarian failure: an experimental approach readdressed.

BACKGROUND: The pathophysiological mechanisms underlying premature ovarian failure (POF) are largely unknown. Our objective was to develop a working animal model to explore the pathogenesis of POF. Since galactosaemic women eventually develop POF, we evaluated the potential of experimental galactose toxicity as the proposed model. METHODS: Pregnant rats were fed pellets supplemented with or without 35% galactose from day 3 of conception continuing through weaning of the litters. Female offspring were evaluated for serum levels of galactose and galactose-1-phosphate, growth rate, onset of puberty, reproductive cyclicity, ovarian complement of follicles, hypothalamo-pituitary-ovarian function and follicular response to gonadotrophins. RESULTS: Galactose toxicity delayed the onset of puberty and developed a state of hypergonadotrophic hypoestrogenism. The characteristic low FSH levels at weaning followed by pubertal spurts of gonadotrophins and estradiol (E(2)) secretion of the controls was replaced by a sustained high level of FSH and a low level of E(2) under galactose toxicity. The ovary developed with apparently normal or deficient complement of follicles. Ovarian response to exogenous gonadotrophin stimulation was blunted, but the response improved significantly when the stimulation was preceded by pituitary desensitization. CONCLUSION: Experimental galactose toxicity may serve as a model for exploring some of the basic tenets of POF.

Aging↗
PubMed1993

Disturbed galactose metabolism in elderly and diabetic humans is associated with cataract formation.

Lactose consumption has been associated with a high incidence of cataract in northern Indian and southern Italian populations. Galactose absorbed after hydrolysis of lactose from milk in individuals with normal lactase activity is considered responsible. However, lactase-deficient subjects who often avoid drinking milk are able to digest lactose and absorb free galactose in fermented milk and yogurt. This study was conducted to evaluate the relationships between milk and yogurt consumption, galactose metabolism and cataract risk. Milk ingestion was dose-related with cataract risk in lactose digesters (particularly in diabetics) but not in lactose maldigesters. Conversely, yogurt intake had a protective dose-effect on cataract formation for the whole population. Maximal galactose concentrations after an oral galactose test increased exponentially with age. Red blood cell galactokinase activity was significantly lower in elderly subjects (> 60 y) than in young individuals (P < 0.05), and galactose-1-phosphate uridyl-transferase activity was significantly lower in institutionalized subjects and in home-living elderly with cataract than in healthy elderly subjects (P < 0.05). We conclude that the cataractogenic action of milk lactose is dependent on the disturbance of galactose metabolism in elderly subjects and that yogurt is not cataractogenic, although the mechanism of the protective effect of yogurt remains unknown.

Adult↗
PubMed1997

BDNF attenuates functional and structural disorders in nerves of galactose-fed rats.

Galactose intoxication of rats was used to disrupt metabolism of Schwann cells and skeletal muscle, two sites that contain the polyol-forming enzyme aldose reductase (AR). Galactose-fed rats develop a neuropathy characterized by nerve conduction deficits and axonal atrophy. To investigate the possibility that galactose metabolism by AR influences axonal function and structure by altering production of neurotrophic factors, the impact of galactose intoxication on nerve and muscle BDNF levels and the effects of exogenous BDNF treatment on galactose neuropathy were examined using biochemical, electrophysiologic and morphometric techniques. Galactose feeding increased BDNF protein in peripheral nerve and muscle. Exogenous BDNF treatment attenuated motor nerve conduction velocity deficits in the sciatic nerve of galactose-fed animals and myelin splitting of motor axons in the ventral root. In contrast, sensory nerve conduction velocity (SNCV) deficits in the sciatic nerve and myelin splitting in the central projections of sensory neurons were not prevented by BDNF treatment. BDNF treatment did not attenuate reduced axonal caliber in the sciatic nerve, but did ameliorate the diminution of the caliber of central sensory projections in the dorsal root. These findings point to the potential use of BDNF in the treatment of peripheral neuropathies.

Aldehyde Reductase↗
PubMed1998

NT-3 attenuates functional and structural disorders in sensory nerves of galactose-fed rats.

The present study investigated the effect of NT-3, a neurotrophin expressed in nerve and skeletal muscle, on myelinated fiber disorders of galactose-fed rats. Adult, female Sprague-Dawley rats were fed diets containing complete micronutrient supplements and either 0% D-galactose (control) or 40% D-galactose. Treated controls received 20 mg/kg NT-3 and treated galactose-fed rats received 1, 5, or 20 mg/kg NT-3 three times per week by subcutaneous injections. After 2 months, sciatic and saphenous sensory nerve conduction velocity (SNCV) and sciatic motor nerve conduction velocity (MNCV) were measured and the sciatic, sural, peroneal and saphenous nerves and dorsal and ventral roots processed for light microscopy. Treatment of control animals with NT-3 had no effect on any functional or structural parameter. Compared to control values, galactose feeding induced a sensory and motor nerve conduction deficit and a reduction in axonal caliber. Treatment with 5 and 20 mg/kg NT-3 ameliorated deficits in sciatic and saphenous SNCV in galactose-fed rats but had no effect on the MNCV deficit. NT-3 treatment also attenuated the decrease in mean axonal caliber in the dorsal root and sural nerve but not in the saphenous nerve, ventral root and peroneal nerve. These observations show that NT-3 can selectively attenuate the sensory conduction deficit of galactose neuropathy in a dose-dependent manner that depends only in part on restoration of axonal caliber of large-fiber sensory neurons.

Animals↗
PubMed1976

Uptake of galactose into Escherichia coli by facilitated diffusion.

Strains of Escherichia coli devoid of systems for the active transport of galactose (galP mgl) still grow on galactose but at rates that are a function of the galactose concentration of the medium: half-maximal growth rates require more than 2 mM-galactose to be present. Evidence is presented that galactose is taken up by such strains by facilitated diffusion on a carrier specified by the umg gene (or by a gene highly co-transducible with it) which is thus a part of, or closely associated with, an enzyme II for glucose of the phosphoenolpyruvate-phosphotransferase system. However, the entry of galactose does not require phosphotransferase activity, and the sugar taken up appears in the cells as free galactose.

Diffusion↗
PubMed1979

Urinary excretion of oligosaccharides induced by galactose given orally or intravenously.

The effect of oral administration of galactose, lactose, and sucrose and intravenous injection of galactose on the urinary excretion of blood-group-active oligosaccharides has been studied. Galactose given either as the free sugar, a glycoside (lactose) or a constituent of normal diet was an absolute requirement for the formation and excretion of A-trisaccharide, B-trisaccharide and 2'-fucosylgalactose in blood group A, B and O(H) secretors, respectively. Great individual variation was seen in the amounts of galactose-dependent oligosaccharides excreted. Injection of galactose resulted in excretion of 3-59% of the amount of oligosaccharide formed after oral administration to the same individual. The mean ratio A-trisaccharide/B-trisaccharide was 2.7 in four blood-group-A1B secretors and 0.22 in three A2B secretors and can thus serve as a parameter for chemical differentiation between the two blood groups. The excretion of larger blood-group-active oligosaccharides, including the A-pentasaccharide, the B-pentasaccharide and lactodifucotetraose, that are normal components in urine from, respectively, starved A, B, and H secretors, was about the same after oral administration of galactose or lactose. The B-trisaccharide was the only oligosaccharide detected in plasma after oral galactose administration to a blood-group-B secretor individual. The concentration was 0.38 mg/l of plasma.

ABO Blood-Group System↗
PubMed1981

UDP-galactose hydrolysis in brain and its effect on cerebroside synthesis.

The enzymatic hydrolysis of UDP-galactose in rat and calf brain was studied. The hydrolysis occurs in two steps: The first is the conversion of UDP-galactose to galactose-1-phosphate catalyzed by nucleotide pyrophosphatase (EC 3.6.1.9), and the second is the conversion of the latter to free galactose by alkaline phosphatase (EC 3.1.3.1). The overall conversion has a pH optimum of 9.0, but there is considerable activity at pH 7.4, which is the optimum for UDP-galactose:ceramide galactosyltransferase in the synthesis of cerebrosides. Preparations from cytosol from calf brain cerebellum or stem that were enriched in UDP-galactose hydrolytic activity inhibit cerebroside synthesis under conditions optimal for the synthesis. Microsome-rich and nuclear debris fractions contain the highest apparent specific activity among the subcellular fractions studied. Hydrolysis of UDP-galactose occurs in all areas of brain, brainstem having the highest activity. The apparent specific activity in jimpy mouse brain homogenate is nearly twice as high as in the control brain homogenate.

Animals↗
PubMed1981

Familial Fanconi syndrome with malabsorption and galactose intolerance, normal kinase and transferase activity. A report on two siblings.

Two siblings of Turkish-Assyrian extraction, whose parents were first cousins, had poor appetite, slow weight gain and retarded psychomotor development. When given milk the galactose concentration in blood increased. An oral galactose load showed a markedly reduced capacity to metabolize galactose. Fanconi syndrome was present as in classical galactosemia. A galactose-free diet reduced the aminoaciduria but did not normalize the renal tubular function nor the children's general condition. Galactokinase and galactose-1-phosphate uridyltransferase activities in red blood cells were normal. The physical appearance of the children (sparse subcutaneous fat, thin extremities and distended abdomen) and the results of vitamin A and xylose absorption tests, were in accordance with a malabsorption condition. Glucose, however, seemed to be absorbed normally from the gut. There was no evidence of primary liver disease. Since the condition did not normalize with a galactose-free diet, an enzyme defect of galactose metabolism is unlikely. Instead, a more general transport defect with autosomal recessive inheritance is proposed.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1968

Dietary regulation of galactose-metabolizing enzymes: adaptive changes in rat jejunum.

The effects of dietary galactose, sucrose, fructose, glucose, casein, and fasting upon the activity of four galactose-metabolizing enzymes (galactokinase, galactose-1-phosphate uridyltransferase, uridine diphosphate galactose 4-epimerase, and galactose dehydrogenase) were studied in the jejunum of rats. Galactose produced the greatest increase in enzyme activity, fructose and sucrose produced effects intermediate between galactose and glucose, and casein produced a greater activity increase than fasting, but less than the sugars.

Alcohol Oxidoreductases↗
PubMed1973

Carbohydrate metabolism in lactic streptococci: fate of galactose supplied in free or disaccharide form.

Phosphorylation of free galactose by lactic streptococci was mediated by an adenosine triphosphate (ATP)-dependent kinase. The phosphoenolpyruvate (PEP) phosphotransferase system (PTS) was involved to a limited extent in transport of the sugar. The conversion of free galactose to glucose also was demonstrated, and uridine diphosphogalactose-4-epimerase was demonstrated to account for this change. Galactose, supplied as lactose, was phosphorylated during transport by means of the PTS with PEP as the phosphate donor. Data also indicated that galactose derived from lactose was catabolized by the glycolytic pathway. Results showed the participation of ATP or PEP, or both, in the phosphorylation of five growth sugars for lactic streptococci, namely, galactose, glucose, lactose, maltose, and mannose. Free galactose was phosphorylated exclusively by ATP except when cells were grown on galactose; in this case, slight involvement of PEP in phosphorylation also was noted. Lactose phosphorylation was much more effective with PEP except when cells were grown on lactose, in which case ATP was equally effective. Glucose was phosphorylated to about the same degree by either ATP or PEP.

Adenosine Triphosphate↗
PubMed1976

Inhibitory action of D-galactose on phagocyte metabolism and function.

To account for enhanced susceptibility to infection among galactosemics, the acute effects of D-galactose on metabolic and functional activities of phagocytic cells in vitro were investigated. Human and guinea pig polymorphonuclear leukocytes (PMN) when incubated in medium containing 30 mM galactose displayed substantially less killing of Escherichia coli than when incubated in medium with 5 mM glucose. Impaired bactericidal activity was dependent upon galactose concentration but could be partially averted by supplementing the galactose-containing medium with 15 mM glucose. Phagocytic activities of guinea pig PMN and peritoneal macrophages were assayed by following ingestion of 32P-labeled E. coli and were also depressed by elevated galactose. Galactose was readily epimerized to glucose by resting PMN, and this conversion was stimulated by phagocytosis. Incubation of macrophages in the presence of galactose resulted in depletion of intracellular levels of adenosine 5' -triphosphate as well as other metabolities.

Adenosine Diphosphate↗
PubMed1969

Resistance of Salmonella typhimurium mutants to galactose death.

A class of galactose-resistant mutants has been derived from strains of Salmonella typhimurium which are defective in uridine diphosphoglucose-4-epimerase. Resistant strains are phenotypically similar to parent organisms but do not lyse in the presence of galactose. Low levels of functional epimerase can be detected in induced cells grown at 20 C but not at 37 C, and acid is not produced from galactose. Sufficient galactose is synthesized at reduced temperatures to fabricate smooth lipopolysaccharide and acceptor sites for phage P22 from galactose-deficient media. The leaky nature of these mutants may account for resistance to galactose death by maintaining galactose metabolites at a subcritical level. Glucose protects sensitive strains by control of levels of toxic metabolites by catabolite repression.

Bacteriolysis↗
PubMed1974

Genetic evidence for the physiological significance of the D-tagatose 6-phosphate pathway of lactose and D-galactose degradation in staphylococcus aureus.

Mutants of Staphylococcus aureus were isolated which were unable to utilize d-galactose or lactose, but which were able to utilize all other carbohydrates tested. Growth of the mutants on a peptone-containing medium was inhibited by d-galactose. Of those mutants selected for further study, one (tagI2) was missing d-galactose 6-phosphate isomerase, one (tagK3) was missing d-tagatose 6-phosphate kinase, and one (tagA4) was missing d-tagatose 1, 6-diphosphate aldolase. Each of these mutants accumulated the substrate of the missing enzyme intracellularly. Spontaneous revertants of each of the mutants simultaneously regained their ability to utilize d-galactose and lactose, lost their sensitivity to d-galactose, regained the missing enzymatic activities, and no longer accumulated intermediates of the d-tagatose 6-phosphate pathway. These data support our previous contention that the physiologically significant route for the metabolism of d-galactose and the d-galactosyl moiety of lactose in S. aureus is the d-tagatose 6-phosphate pathway. Furthermore, a mutant constitutive for all three enzymes of this pathway was isolated, indicating that the products of the tagI, tagK, and tagA genes are under common genetic control. This conclusion was supported by the demonstration that d-galactose 6-phosphate isomerase, d-tagatose 6-phosphate kinase, and d-tagatose 1, 6-diphosphate aldolase are coordinately induced in the parental strain.

Aldehyde-Lyases↗
PubMed1977

Galactose transport in Salmonella typhimurium.

We have studied the various systems by which galactose can be transported in Salmonella typhimurium, in particular the specific galactose permease (GP). Mutants that contain GP as the sole galactose transport system have been isolated, and starting from these mutants we have been able to select point mutants that lack GP. The galP mutation maps close to another mutation, which results in the constitutive synthesis of GP, but is not linked to galR. Growth of wild-type strains on glaactose induces GP but not the beta-methylgalactoside permease (MGP). Strains lacking GP are able to grow slowly on galactose, and MGP is induced; however, D-fucose is a much better inducer of MGP. Induction of GP or MGP is not prevented by a pts mutation, although this mutation changes the apparent Km of MGP for galactose. pts mutations have no effect on GP. GP has a rather broad specificity: galactose, glucose, mannose, fucose, 2-deoxygalactose, and 2-deoxyglucose are substrates, but only galactose and fucose can induce this transport system.

Biological Transport, Active↗
PubMed1980

Characterization and regulation of galactose transport in Neurospora crassa.

Two galactose uptake systems were found in the mycelia of Neurospora crassa. In glucose-grown mycelia, galactose was transported by a low-affinity (Km = 400 mM) constitutive system which was distinct from the previously described glucose transport system I (R. P. Schneider and W. R. Wiley, J. Bacteriol. 106:479--486, 1971). In carbon-starved mycelia or mycelia incubated with galactose, a second galactose transport activity appeared which required energy, had a high affinity for galactose (Km = 0.7 mM), and was shown to be the same as glucose transport system II. System II also transported mannose, 2-deoxyglucose, xylose, and talose and is therefore a general monosaccharide transport system. System II was derepressed by carbon starvation, completely repressed by glucose, mannose, and 2-deoxyglucose, and partially repressed by fructose and xylose. Incubation with galactose yielded twice as much activity as starvation. This extra induction by galactose required protein synthesis, and represented an increase in activity of system II rather than the induction of another transport system. Glucose, mannose, and 2-deoxyglucose caused rapid degradation of preexisting system II; fructose and xylose caused a slower degradation of activity.

Biological Transport, Active↗
PubMed1980

Galactose transport systems in Streptococcus lactis.

Galactose-grown cells of Streptococcus lactis ML3 have the capacity to transport the growth sugar by two separate systems: (i) the phosphoenolpyruvate-dependent phosphotransferase system and (ii) an adenosine 5'-triphosphate-energized permease system. Proton-conducting uncouplers (tetrachlorosalicylanilide and carbonyl cyanide-m-chlorophenyl hydrazone) inhibited galactose uptake by the permease system, but had no effect on phosphotransferase activity. Inhibition and efflux experiments conducted using beta-galactoside analogs showed that the galactose permease had a high affinity for galactose, methyl-beta-D-thiogalactopyranoside, and methyl-beta-D-galactopyranoside, but possessed little or no affinity for glucose and lactose. The spatial configurations of hydroxyl groups at C-2, C-4, and C-6 were structurally important in facilitating interaction between the carrier and the sugar analog. Iodoacetate had no inhibitory effect on accumulation of galactose, methyl-beta-D-thiogalactopyranoside, or lactose via the phosphotransferase system. However, after exposure of the cells to p-chloromercuribenzoate, phosphoenolpyruvate-dependent uptake of lactose and methyl-beta-D-thiogalactopyranoside were reduced by 75 and 100%, respectively, whereas galactose phosphotransferase activity remained unchanged. The independent kinetic analysis of each transport system was achieved by the selective generation of the appropriate energy source (adenosine 5'-triphosphate or phosphoenolpyruvate) in vivo. The maximum rates of galactose transport by the two systems were similar, but the permease system exhibited a 10-fold greater affinity for sugar than did the phosphotransferase system.

Adenosine Triphosphate↗