Disease relevance of D-Galactose 1-phosphate

• Galactosemia: alterations in sulfate metabolism secondary to galactose-1-phosphate uridyltransferase deficiency [1].
• In a case-control study, consumption of dairy foods by 235 white women with epithelial ovarian cancer and by 239 control women, and activity of red blood cell galactose-1-phosphate uridyl transferase (transferase) in a subset of 145 cases and 127 controls were determined [2].
• The nucleotide sequences of the gal E gene coding for UDP-galactose-4-epimerase and the gal T gene coding for galactose-1-P uridyltransferase of Escherichia coli have been determined [3].
• A patient with neonatal jaundice and cirrhosis who was previously reported homozygous for the Durate variant of galactose-1-phosphate uridyl transferase has the ZZ genotype for alpha1-antitrypsin [4].
• Mutation of galactose-1-phosphate uridyl transferase and its association with ovarian cancer and endometriosis [5].

Psychiatry related information on D-Galactose 1-phosphate

• The sequence of At5g18200.1 indicates a distant family relationship to the Escherichia coli galactose-1-P uridylyltransferase (GalT): the determined structure of the At5g18200.1 protein confirms this relationship [6].
• An 8-year-old boy with galactose-1-phosphate uridyl transferase (GALT) deficiency presented with hypotonia, muscle hypotrophy, hepatomegaly, bilateral cataract and mild mental retardation [7].
• PURPOSE: This study evaluates a genotype/phenotype relationship between developmental verbal dyspraxia (DVD) and the common, missense mutation of the galactose-1-phosphate uridyltransferase gene, Q188R, in patients with classic galactosemia (G/G) [8].
• We report a case of galactose-1-phosphate uridyl transferase (GALT) deficiency in a full-term Chinese neonate, who presented with atypical biochemical features of hyperammonaemia in addition to the classical presenting features of jaundice and lethargy after feeding [9].

High impact information on D-Galactose 1-phosphate

• Clinical course and mean erythrocyte galactose-1-phosphate and urinary galactitol levels did not correlate with ovarian function [10].
• Cultures of nonmutant as well as galactokinase-deficient fibroblasts incorporate 20 percent more [35S]sulfate when galactose is substituted for glucose in the medium; galactose-1-phosphate uridyltransferase-deficient cells incorporate 65.5 percent less [1].
• Human orythrocytes that are homozygous for the Duarte enzyme variant of galactosemia (D/D) have a characteristic isoform on isoelectric focusing and 50% reduction in galactose-1-phosphate uridyltransferase (GALT) enzyme activity [11].
• Evaluation of a family in which electrophoretic variants of the eznyme galactose-1-phosphate uridyl transferase (GALT) and 9qh variants occur demonstrates close linkage between these two traits: lod score of 3.67 at theta = 0 [12].
• Assignment of the human gene for galactose-1-phosphate uridyltransferase to chromosome 9: studies with Chinese hamster-human somatic cell hybrids [13].

Chemical compound and disease context of D-Galactose 1-phosphate

• Galactosemia is a human inborn error of galactose metabolism due to deficiency of galactose-1-phosphate uridyl transferase [14].
• Our results demonstrate that the enzyme transfers in vitro a galactose-1-phosphate from UDP-galactose to endogenous phosphoryl-polyprenol and that the C-terminal half of WsaP carries the galactosyltransferase function, as already observed for the UDP-Gal:phosphoryl-polyprenol Gal-1-phosphate transferase WbaP from Salmonella enterica [15].
• Uridine-containing sugar nucleotides, uridine diphosphate (UDP)-glucose and UDPgalactose are important intermediates in galactose metabolism, and tissue UDPgalactose may be a salient factor in the etiology of the long-term clinical manifestations of patients with galactose-1-phosphate uridyltransferase deficient galactosemia [16].
• We evaluated 132 galactosemia patients for the Q188R (glutamine-188 to arginine) mutation in the human galactose-1-phosphate uridyltransferase (GALT) gene and for GALT activity in their hemolysates by a sensitive radioisotopic method [17].
• A fusion enzyme consisting of UDP-galactose 4-epimerase and galactose-1-P uridylyltransferase with an intervening Ala3 linker was constructed by in-frame fusion of E. coli gene galT to the 3'-terminus of the E. coli gene galE that had been extended with the coding sequence for three alanine residues, all contained within a high-expression plasmid [18].

Biological context of D-Galactose 1-phosphate

• Chinese hamster-human somatic cell hybrids were analyzed for the expression of human galactose-1-phosphate uridyltransferase (GALT; UDPglucose:alpha-D-galactose-1-phosphate uridyltransferase, EC 2.7.7.12) by electrophoresis and for the presence of human chromosomes cytogenetically with the aid of Q-banding [13].
• The post-translational modification of proteins by nonenzymatic galactosylation may be of physiological significance in individuals with reduced galactokinase or galactose-1-phosphate uridyl transferase activities [19].
• Classical galactosemia is caused by one common missense mutation (Q188R) and by several rare mutations in the galactose-1-phosphate uridyltransferase (GALT) gene [20].
• Galactokinase (GalK) catalyses the first step of the Leloir pathway of galactose metabolism, the ATP-dependent phosphorylation of galactose to galactose-1-phosphate [21].
• Confirmation of the cytogenetic interpretation was obtained from the assay of the enzyme galactose-1-P uridyl transferase, the locus for which is on 9p, which showed twice the normal activity [22].

Anatomical context of D-Galactose 1-phosphate

• The activity of galactose-1-phosphate uridyltransferase (transferase) and galactokinase in several organs from human fetuses 7-28 weeks old was measured by using radioactive substrates and column chromatography for product identification [23].
• We compared galactose-1-phosphate uridyltransferase among erythrocytes, leukocytes, and transformed lymphoblasts, as well as total body oxidation of D-(13C)-galactose to 13CO2 among three genotypes for GALT (S135L/S135L, Q188R/Q188R, and Normal/Normal) [24].
• Characteristics of galactokinase and galactose-1-phosphate uridyltransferase in cultivated fibroblasts and amniotic fluid cells [25].
• Galactose-1-phosphate was not detectable in umbilical cord blood from one infant [26].
• Clinical and biochemical evidence of skeletal muscle involvement in galactose-1-phosphate uridyl transferase deficiency [7].

Associations of D-Galactose 1-phosphate with other chemical compounds

• Other data demonstrate that lac10c mutations have pleiotrophic effects, there being constitutive levels not only of beta-galactosidase activity, but also the other lactose-inducible activities of galactokinase (EC 2.7.5.1), galactose-1-phosphate uridyl transferase (EC 2.7.7.10), and lactose transport [27].
• However, recent findings of lower average red blood cell (RBC) UDPgalactose concentrations in galactose-1-phosphate uridyltransferase-deficient patients suggest that other factors play a role in determining its concentration [28].
• The associations were analyzed between POF and the mutations in GALT, the highest erythrocyte galactose-1-phosphate (Gal-1-P) level at diagnosis, the age at which dietary treatment was initiated, mean erythrocyte Gal-1-P level during treatment, and whole-body carbon 13-labeled galactose oxidation to (13)CO(2) [29].
• In vitro biochemical analysis showed that UDP-glucose pyrophosphorylase had bifunctional properties and could catalyze the conversion of galactose-1-phosphate to UDP-galactose in the presence of UTP [30].
• This difference disappeared when the N/N tissue homogenate was dialyzed to remove residual UDP-glucose, confirming that careful elimination of residual GALT activity is necessary, since GALT has 1000-fold greater activity toward galactose-1-phosphate than that of UDP-galPP in liver homogenates [31].

Gene context of D-Galactose 1-phosphate

• A sequence of pedigree, biochemical, and molecular analyses of the galactose-1-phosphate uridyltransferase (GALT) enzyme and genetic locus in both affected and carrier individuals revealed three distinct base substitutions in this family, two (Q188R and S135L) that had been reported previously and one (V151A) that was novel [32].
• By complementing appropriate gal lesions in Escherichia coli K802, we were able to isolate the galactokinase (galK) and galactose-1-phosphate uridyl transferase (galT) genes of Lactobacillus helveticus [33].
• We present the nucleotide sequence of a 1599-base pair (bp) DNA fragment containing the entire GAL7 gene that encodes galactose-1-phosphate uridyltransferase of Saccharomyces cerevisiae [34].
• It activates Gal4p by interacting with Gal80p--a function that can also served by Gal3p--and it catalyzes the formation of galactose-1-phosphate [35].
• Screening of 46 742 newborns yielded 1 false-positive result (in a heterozygous carrier), 1 patient with glucose-6-phosphate dehydrogenase deficiency, and no apparent false negatives as judged by concurrent measurements of galactose and galactose-1-phosphate [36].

Analytical, diagnostic and therapeutic context of D-Galactose 1-phosphate

• We identified 14 mutations in 15 Japanese subjects from 13 families with galactose-1-phosphate uridyltransferase (GALT) deficiency using denaturing gradient gel electrophoresis (DGGE) and direct sequence analysis [37].
• Newborn galactosemia screening programs using the fluorescence spot test to detect red cell galactose-1-phosphate uridyltransferase activity are prone to inaccuracy if the screened infants have received blood transfusions [38].
• The red blood cell (RBC) concentration of galactitol and galactonate was measured in 27 patients with galactose-1-phosphate uridyltransferase (GALT) deficiency galactosemia and 19 non-galactosemic subjects by a newly devised isotope dilution gas chromatography/mass spectrometry (GC/MS) method [39].
• Assay of galactose-1-phosphate uridyl transferase in cultured amniotic cells for prenatal diagnosis of galactosaemia [40].
• Starch gel electrophoresis for galactose-1-phosphate uridylyl-transferase applied to dried filter paper blood specimens [41].

References