Disease relevance of galactitol

• Furthermore, our findings suggest that the inositol depletion associated with sorbitol or galactitol accumulation in various cell types during hyperglycemia may be a function of cellular osmoregulation [1].
• Dulcitol similarly accumulates in the presence of galactosemia [2].
• In humans, GK deficiency results in congenital cataracts due to an accumulation of galactitol within the lens [3].
• Molecular analysis of the gat genes from Escherichia coli and of their roles in galactitol transport and metabolism [4].
• Using in vivo proton magnetic resonance spectroscopy, we detected approximately 8 mmol galactitol per kilogram of brain tissue, an amount potentially relevant to the pathogenesis of brain edema [5].

High impact information on galactitol

• Moreover, galactose feeding results in changes in tissue AR activities that are not related, temporally or quantitatively, to the alterations in tissue AR mRNA or galactitol levels [6].
• There were no large differences observed in survival sensitivities anywhere in the cell cycle, suggesting that galactitol was not a cell-cycle phase-specific agent [7].
• Synchronized mitotic and G1 phase cells were equally sensitive to galacitol, with approximately 90% of the cells killed by 1-hour exposures to 12.5 mug galactitol/ml [7].
• Cells in mitosis or G1 phases of the cell cycle at the time of treatment with galacitol progressed normally into the next stage of the cell cycle; however, cells exposed to galactitol in S or G2 phases exhibited dose-dependent delays in those phases of the cell cycle [7].
• In addition, both galactose and galactitol accumulated in tissues of GK-deficient mice [3].

Chemical compound and disease context of galactitol

• Pasteurella multocida is composed of three subspecies that are often differentiated by fermentation of sorbitol and dulcitol [8].
• Among the five families of EIIs identified in Escherichia coli, the galactitol-specific transporter (II(gat)) belongs to the glucitol family and is structurally the least well-characterized [9].
• In enteric bacteria, the hexitol galactitol (Gat) (formerly dulcitol) is taken up through enzyme II (II(Gat)) of the phosphoenolpyruvate-dependent phosphotransferase system (PTS), and accumulated as galactitol 1-phosphate (Gat1P) [4].
• The data suggest that high galactose 1-phosphate levels do not cause galactose toxicity and that high galactitol in combination with galactose 1-phosphate may be a prerequisite [10].
• Plasma galactose and galactitol concentration in patients with galactose-1-phosphate uridyltransferase deficiency galactosemia: determination by gas chromatography/mass spectrometry [11].

Biological context of galactitol

• These retain the DeltaagaW' EF 'A deletion and carry suppressor mutations in the gat and nag genes for galactitol and N-acetyl-glucosamine metabolism, respectively, that allow growth on Aga but not on GalN [12].
• Excreted amounts of galactose and galactitol increased with age in all subjects, but were consistently greater in the compound heterozygotes [13].
• Examination of the deletion mutants for phenotype revealed novel loci required for dulcitol, melibiose, raffinose, beta-hydroxybutyrate, acetoacetate, protocatechuate and quinate utilization [14].
• (iii) Mutations affecting the transport and catabolism of galactitol are clustered in a third operon, gatC A D, located at 40.5 min [15].
• Physical characterization of lambda specialized transducing phages carrying the ribitol-arabitol or galactitol genes demonstrates that this exclusion results because these genes have identical locations in their respective chromosomes [16].

Anatomical context of galactitol

• When the transgenic mice were fed food containing 30% galactose, significant levels of galactitol accumulated in the sciatic nerve [17].
• The galactitol content of the sorbinil-treated cells was significantly reduced compared with the galactitol levels in cells cultured in 30 mM galactose; however, galactitol levels remained significantly elevated over control cells [18].
• Galactose-fed dogs had a remarkable accumulation of galactitol in their aortas [19].
• After 44 months, morphometric analyses of coronary arteries were carried out and the galactitol contents in aortas were measured [19].
• Erythrocyte and retinal galactitol levels were decreased by 91% and 95%, respectively, with inhibitor treatment [20].

Associations of galactitol with other chemical compounds

• Galactose feeding resulted in a great accumulation of galactitol and reduction in AR mRNA levels in renal papillae [1].
• They also demonstrated collateral resistance to Actinomycin D, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, galactitol, and X-rays, but showed no change in sensitivity to 5-fluorouracil, bleomycin, and Adriamycin [21].
• Accumulation of galactitol in the nerves of galactose-fed mice was prevented by aldose reductase inhibition, but there were no alterations in myo-inositol levels in the sciatic nerves of any group [22].
• Compounds within these series were evaluated in vitro for their ability to inhibit glyceraldehyde reduction by bovine lens aldose reductase and in vivo by their ability to inhibit galactitol accumulation in the lens and sciatic nerve of galactose-fed rats [23].
• Measurements were made under aerobic and anaerobic conditions of lactic acid production, retinal adenosine triphosphate (ATP), lactic acid content, the hexose monophosphate shunt pathway, aldose reductase activity, and levels of sorbitol and galactitol [24].

Gene context of galactitol

• In this pathway, galactitol is catabolised by the lad1-encoded l-arabinitol-4-dehydrogenase, because a gal1/lad1 double delta-mutant failed to grow on d-galactose [25].
• Other genes coding for two additional enzymes involved in galactitol catabolism apparently are not linked to gatC A D [15].
• In SORD-deficient patients, the enzymatic deficiency was observed in both crude haemolysate and SORD-M preparations with sorbitol, galactitol, xylitol or ribitol as substrates [26].
• There was correlation between galactitol levels and aldose reductase levels [27].
• Erythritol, threitol, ribitol, arabitol, and galactitol are polyols found in variable quantities in these tissues, which have a variable influence on the activity of sorbitol dehydrogenase and therefore alter sorbitol quantitation with this enzyme [28].

Analytical, diagnostic and therapeutic context of galactitol

• HPLC analysis of lens tissue indicated progressive accumulation of galactitol, 18 mM after 3 days, which plateaued to about 30 mM between 6 and 14 days [29].
• This stable isotope dilution assay is a rapid accurate method for measurement of galactitol in amniotic fluid for prenatal diagnosis of galactosemia [30].
• Galactitol levels in the lens epithelium were quantified by gas chromatography [31].
• There was no difference in the levels of RBC galactitol, galactonate, and Gal-1-P between D/G newborns on a lactose-restricted diet and the control group [32].
• The levels of lens aldose reductase activity, galactitol and the onset of cataract were evaluated during and after treatment with the inhibitor.Topical application of 1-3% Tolrestat (10 microl) four times daily resulted, after 9 days, in a significant decrease in the enzyme activity [33].

References