Disease relevance of GALE

• Identification and characterization of a mutation, in the human UDP-galactose-4-epimerase gene, associated with generalized epimerase-deficiency galactosemia [1].
• Unlike the Escherichia coli enzyme, human GALE (hGALE) also efficiently interconverts a larger pair of substrates: UDP-N-acetylgalactosamine and UDP-N-acetylglucosamine [2].
• Comment on: Gale EAM (2005) Latent autoimmune diabetes in adults: a guide for the perplexed. Diabetologia 48:2195-2199 [3].
• Accordingly, cell lines inducibly expressing NS5A were found to rescue EMCV growth (S. J. Polyak, D. M. Paschal, S. McArdle, M. J. Gale, Jr., D. Moradpour, and D. R. Gretch, Hepatology 29:1262-1271, 1999) [4].
• The amino acid sequence of the enzyme showed a significant similarity to that of UDP-glucose 4-epimerase from Staphylococcus aureus and belongs to the short-chain dehydrogenase-reductase superfamily [5].

High impact information on GALE

• The specific activity of the V94M-hGALE protein expressed in yeast was severely reduced with regard to UDP-galactose and partially reduced with regard to UDP-N-acetylgalactosamine [1].
• UDP-galactose-4-epimerase (GALE) is a highly conserved enzyme that catalyzes the interconversion of UDP-galactose and UDP-glucose [6].
• Furthermore, we have expressed and characterized two mutant alleles, L183P-hGALE and N34S-hGALE, both derived from a patient with no detectable GALE activity in red blood cells but with approximately 14% activity in cultured lymphoblasts [6].
• Reversal of UDP-galactose 4-epimerase deficiency of human leukocytes in culture [7].
• Possible explanations for the appearance of UDP-galactose 4-epimerase activity in stimulated lymphocytes include an increased rate of synthesis of a mutant enzyme and a derepression of an epimerase locus during lymphocyte transformation [7].

Chemical compound and disease context of GALE

• Epimerase deficiency galactosemia is an autosomal recessive condition resulting from the impairment of UDP-galactose 4'-epimerase (hGALE) [8].

Biological context of GALE

• Together, these results serve to validate the wild-type hGALE crystal structure and fully support the hypothesis that residue 307 acts as a gatekeeper mediating substrate access to the hGALE active site [2].
• The biosynthesis gene cassette was a approximately 4.2-kb region located between ctrA of the capsule transport operon and galE, which encodes the UDP-glucose-4-epimerase [9].
• During Dr. Gale Gardner's tenure as Committee chairman, manuscripts were reviewed and edited by Dr. Nels Olson, and The American Journal of Otology agreed to publish the manual [10].
• UDP-galactose-4-epimerase in a boy with a trisomy 21 [11].
• Inherited deficiencies of UDP-galactose 4-epimerase (GALE) have been associated with two distinct phenotypes [12].

Anatomical context of GALE

• The gene I12A1, which codes for a UDP-glucose 4-epimerase homolog, was identified as a putative target gene within the prt7.1/brt7.1 QTL region, as it is involved in the cell wall biogenesis pathway and hence may be implicated in modulating the ability of rice roots to penetrate further into the substratum when exposed to drought conditions [13].
• Masticatory muscle pain level was determined by muscle palpation, scored on a scale of 0 to 3 each period, according to the method of Gross and Gale [14].

Associations of GALE with chemical compounds

• Human UDP-galactose 4-epimerase. Accommodation of UDP-N-acetylglucosamine within the active site [15].
• A structural comparison of ADP-hep 6-epimerase with UDP-galactose 4-epimerase, which utilizes an NAD(+) cofactor, has identified the regions of ADP-hep 6-epimerase, which defines its specificity for NADP(+) [16].
• Comment on: Gale EAM (2005) Spring harvest? Reflections on the rise of type 1 diabetes. Diabetologia 48:2245-2250; and Walker M, Mari A, Jayapaul MK et al (2005) Impaired beta cell glucose sensitivity and whole-body insulin sensitivity as predictors of hyperglycaemia in non-diabetic subjects. Diabetologia 48:2470-2476 [17].
• 13C NMR analysis of electrostatic interactions between NAD+ and active site residues of UDP-galactose 4-epimerase: implications for the activation induced by uridine nucleotides [18].
• The aetiology among transient cases was unknown in 55, delayed closure of the ductus venosus in 19, heterozygous UDP-galactose 4-epimerase (GALE) deficiency in 16, and heterozygous galactose-1-phosphate uridyltransferase (GALT) deficiency in 6 [19].

Other interactions of GALE

• [1-14C]Galactose oxidation was normal in erythrocytes, but reduced in fresh minced liver tissue, despite normal activities of hepatic galactokinase, uridyltransferase, and UDP-glucose 4-epimerase in homogenates of frozen liver [20].
• An efficient method to assay both UDP-glucose pyrophosphorylase and UDP-glucose-4-epimerase in a crude extract of the red seaweed, Solieria chordalis is described [21].
• This method contains two coupling enzymes of UDP-galactose-4-epimerase and UDP-glucose dehydrogenase, and conversion of NAD to NADH [22].

Analytical, diagnostic and therapeutic context of GALE

• A new mass screening method of detecting UDP-galactose-4-epimerase deficiency [23].
• The aim of this study was to compare porphyrin levels in leukemic patients undergoing chemotherapy or not.We analysed porphyrin values in patients with acute emyelogenous leukemia, who had or had not received chemotherapy according to Gale [24].
• An HPLC method for the assay of UDP-glucose pyrophosphorylase and UDP-glucose-4-epimerase in Solieria chordalis (Rhodophyceae) [21].

References