Disease relevance of Udpgal

• We suggest that coupling the operon's constitutive promoter to the galE gene fulfills a physiological requirement for constitutive UDPgalactose 4-epimerase expression in Streptomyces [1].
• To test the hypothesis that the amount of galactose traversing the Leloir pathway contributes to the cellular UDPgalactose pool, we determined RBC UDPgalactose in patients with maple syrup urine disease (MSUD), phenylketonuria (PKU), and other metabolic diseases who were treated with a low-protein, and consequently, low-lactose diet [2].
• UDPgalactose 4-epimerase from Escherichia coli is rapidly inactivated by the compounds uridine 5'-diphosphate chloroacetol (UDC) and uridine 5'-diphosphate bromoacetol (UDB) [3].
• Defective galactosylation in galactosemia: is low cell UDPgalactose an explanation [4]?
• UDPgalactose epimerase in lens and fibroblasts: activity expression in patients with cataracts and mental retardation [5].

High impact information on Udpgal

• Third, addition of the GalTase catalytic substrate, UDPgalactose, produced a dose-dependent increase in the rate of cell migration [6].
• A variety of galactosyltransferase perturbants, including anti-galactosyltransferase antibodies, UDPgalactose, and the substrate modifier protein alpha-lactalbumin, inhibited the growth of F9 cells, whereas control reagents did not [7].
• Galactose supplementation of MSUD patients significantly increased their UDPgalactose concentrations in both RBCs and white blood cells (WBCs) from 29.5 +/- 1.5 to 42.3 +/- 5.8 nmol/g hemoglobin and from 69.0 +/- 7.5 to 193.0 +/- 49.0 nmol/g protein, respectively [2].
• In the presence of UDPgalactose, but not other sugar nucleotides, EC cell adhesion is reduced and preformed cell adhesions are dissociated [8].
• UDPgalactose inhibits blastocyst formation in the mouse. Implications for the mode of action of T/t-complex mutations [9].

Chemical compound and disease context of Udpgal

• Leukocyte UDPgalactose and UDPglucose values were determined in 60 normal individuals, 14 classic galactosemics, and 18 patients with other metabolic diseases on protein-restricted and low-lactose diets [10].
• By limiting galactosylation mechanisms, a cellular deficiency of the uridine sugar nucleotide, UDPgalactose, has been implicated as a cause of the long-term complications seen in patients with classic galactosemia despite dietary treatment [11].

Biological context of Udpgal

• No difference in cell growth or [3H]thymidine uptake was detected after 6 hours of exposure to UDPgalactose, but both were significantly decreased at 24 and 48 hours [12].
• Inhibition of either UDPgalactose hydrolysis or beta-galactosidase had no effect on galactosyltransferase activity [13].
• In calf serum supplemented Dulbecco's medium (CS-DMEM), 1.2 mM UDPgalactose (UDPgal) inhibited cell growth by 50% (IC50), and 5 mM UDPgalactose inhibited cell growth by 92% [12].
• Flow cytometric analysis of UDPgalactose effects on L1210 cells revealed no differences in the distribution of cells in G1, S, or G2-M of the cell cycle after 6 hours of incubation, but after 16 hours of UDPgalactose treatment, L1210 cells were arrested in early S phase [12].
• Its deduced amino acid sequence showed a high homology with monogalactosyldiacylglycerol synthase (UDPgalactose: 1,2-diacylglycerol 3-beta-D-galactosyl transferase; EC 2.4.1.46, MGDG synthase) from Arabidopsis thaliana; therefore, we named the gene OsMGD [14].

Anatomical context of Udpgal

• In order to characterize the activity of brain UDPgalactose: ceramide galactosyltransferase (CGalT), it has been stably expressed in CGalT-negative Chinese hamster ovary (CHO) cells [15].
• The data suggest that UDPgalactose inhibition of cell growth requires extracellular galactosyltransferase activity and that the effect is mediated via the cell membrane [12].
• 31P NMR spectra of intact red blood cells: quantitation of UDPGlucose and UDPGalactose [16].
• The fact that galactosemic fibroblasts demonstrate no abnormality in the concentration of these compounds suggests that the defective galactosylation that has been observed in galactosemic fibroblasts is not due to unavailability of UDPgalactose [10].
• Effect of estradiol and progesterone on UDPgalactose pyrophosphatase activity in the endometrium of ovariectomized rats [17].

Associations of Udpgal with other chemical compounds

• Uridine nucleotides, which inhibit galactosyltransferase activity, protected L1210 cells from the growth inhibitory effect of UDPgalactose when both were added simultaneously to culture media [12].
• Enhancement of UDPgalactose: glycoprotein galactosyltransferase in cultured human skin fibroblasts by cationic polypeptides [18].
• Product analysis suggested that UDPgalactose hydrolysis was due to nucleotide-sugar pyrophosphatase and galactose-1-phosphate phosphatase activities; ileum appeared to have little of the first activity and none of the latter [19].
• The specific radioactivity of UDPgalactose, when integrated over the whole period of radioactive synthesis, was four times higher in the galactosamine-treated animals than in the controls; the corresponding ratio of UDPglucose was 0.85 [20].

Gene context of Udpgal

• The modulation of UDPglucose and UDPgalactose concentrations, occurring after the presentation of galactose to cells, as a result of the combined actions of GALT and UDPgalactose-4-epimerase, may be important in determining rates of synthesis of complex glycoconjugates [21].
• The distribution and partial characterization of UDPgalactose: N-acetylgalactosamine mucin galactosyltransferase activity from rat small intestine and its sensitivity to Zn2+ [22].
• These results demonstrate that the S. cerevisiae UDPgalactose 4-epimerase is a bifunctional enzyme with aldose 1-epimerase activity [23].
• Impairment of the human enzyme UDPgalactose 4-epimerase (hGALE) results in epimerase-deficiency galactosaemia, an inborn error of metabolism with variable biochemical presentation and clinical outcomes reported to range from benign to severe [24].
• The levels of UDPglucose and UDPgalactose (UDPGal) have been measured in erythrocytes of seven patients with galactokinase deficiency [25].

Analytical, diagnostic and therapeutic context of Udpgal

• The concentration of red blood cell UDPglucose and UDPgalactose determined by high-performance liquid chromatography [26].
• 31P NMR analysis of red blood cell UDPGlucose and UDPGalactose: comparison with HPLC and enzymatic methods [27].
• Sequence analysis indicates that the yeast epimerase has an N-terminal domain (residues 1-377) that shows significant similarity with Escherichia coli and human UDPgalactose 4-epimerase, and a C-terminal domain (residues 378-699), which shows extensive identity to either the bacterial or human aldose 1-epimerase (mutarotase) [23].
• Addition of Zn2+ (4 mM) to assays containing Mn2+ (20 mM) did not cause appreciable UDPgalactose breakdown, as measured by high-voltage paper electrophoresis, suggesting that Zn2+ inhibition is not a result of pyrophosphatase activation [22].

References