utp hexose 1 phosphate uridylyltransferase


Summary: An enzyme that catalyzes the synthesis of UDPgalactose from UTP and galactose-1-phosphate. It is present in low levels in fetal and infant liver, but increases with age, thereby enabling galactosemic infants who survive to develop the capacity to metabolize galactose. EC

Top Publications

  1. Reichardt J, Levy H, Woo S. Molecular characterization of two galactosemia mutations and one polymorphism: implications for structure-function analysis of human galactose-1-phosphate uridyltransferase. Biochemistry. 1992;31:5430-3 pubmed
    ..Our data further support the notion of molecular heterogeneity of galactosemia and suggest that galactosemia mutations and GALT polymorphisms may be useful tools in highlighting different functional domains in human GALT...
  2. Murphy M, McHugh B, Tighe O, Mayne P, O NEILL C, Naughten E, et al. Genetic basis of transferase-deficient galactosaemia in Ireland and the population history of the Irish Travellers. Eur J Hum Genet. 1999;7:549-54 pubmed
    ..This represents the first molecular genetic description of classical transferase-deficient galactosaemia in Ireland and raises intriguing questions concerning the genetic history of the Irish Travellers...
  3. Reichardt J, Woo S. Molecular basis of galactosemia: mutations and polymorphisms in the gene encoding human galactose-1-phosphate uridylyltransferase. Proc Natl Acad Sci U S A. 1991;88:2633-7 pubmed
    ..It appears that galactosemia mutations tend to occur in regions that are highly conserved throughout evolution while the polymorphisms change variable residues...
  4. Kozak L, Francova H, Pijackova A, Macku J, Stastna S, Peskovová K, et al. Presence of a deletion in the 5' upstream region of the GALT gene in Duarte (D2) alleles. J Med Genet. 1999;36:576-8 pubmed
  5. Trbusek M, Francova H, Kozak L. Galactosemia: deletion in the 5' upstream region of the GALT gene reduces promoter efficiency. Hum Genet. 2001;109:117-20 pubmed
    ..We conclude that the -119/-116delGTCA promoter mutation is a crucial factor in reduction of Duarte allele enzyme activity...
  6. Calderon F, Phansalkar A, Crockett D, Miller M, Mao R. Mutation database for the galactose-1-phosphate uridyltransferase (GALT) gene. Hum Mutat. 2007;28:939-43 pubmed
    ..This free online scientific resource was developed with the clinical laboratory in mind to serve as a reference and repository for novel findings that are periodically collected, verified, and updated into the database...
  7. Lai K, Langley S, Singh R, Dembure P, Hjelm L, Elsas L. A prevalent mutation for galactosemia among black Americans. J Pediatr. 1996;128:89-95 pubmed
    ..To define the mutation causing galactosemia in patients of black American origin who have no galactose-1-phosphate uridyltransferase (GALT) activity in erythrocytes but good clinical outcome...
  8. Elsas L, Lai K, Saunders C, Langley S. Functional analysis of the human galactose-1-phosphate uridyltransferase promoter in Duarte and LA variant galactosemia. Mol Genet Metab. 2001;72:297-305 pubmed
    ..The -119 to -116delGTCA reduces hGALT transcription resulting in reduced GALT activity in the Duarte allele...
  9. Suzuki M, West C, Beutler E. Large-scale molecular screening for galactosemia alleles in a pan-ethnic population. Hum Genet. 2001;109:210-5 pubmed

More Information


  1. Langley S, Lai K, Dembure P, Hjelm L, Elsas L. Molecular basis for Duarte and Los Angeles variant galactosemia. Am J Hum Genet. 1997;60:366-72 pubmed
    ..A favorable codon bias for the mutated codon with consequently increased translation rates is postulated as the mechanism...
  2. Podskarbi T, Kohlmetz T, Gathof B, Kleinlein B, Bieger W, Gresser U, et al. Molecular characterization of Duarte-1 and Duarte-2 variants of galactose-1-phosphate uridyltransferase. J Inherit Metab Dis. 1996;19:638-44 pubmed
    ..The G1391A mutation may affect another cis-acting regulatory sequence. Alternatively, both mutations may be involved in an aberrant splice processing, which possibly results in a low level of correctly spliced mRNA...
  3. Lin H, Kirby L, Ng W, Reichardt J. On the molecular nature of the Duarte variant of galactose-1-phosphate uridyl transferase (GALT). Hum Genet. 1994;93:167-9 pubmed
    ..We suggest that N314D encodes the D variant of GALT and that molecular testing for N314D might be useful to confirm a biochemical diagnosis of Duarte variant of GALT...
  4. Ashino J, Okano Y, Suyama I, Yamazaki T, Yoshino M, Furuyama J, et al. Molecular characterization of galactosemia (type 1) mutations in Japanese. Hum Mutat. 1995;6:36-43 pubmed
  5. Leslie N, Immerman E, Flach J, Florez M, Fridovich Keil J, Elsas L. The human galactose-1-phosphate uridyltransferase gene. Genomics. 1992;14:474-80 pubmed
    ..The most common of these is an A to G transition at nucleotide position 1470, converting a glutamine to an arginine at amino acid codon position 188 (Q188R).(ABSTRACT TRUNCATED AT 250 WORDS) ..
  6. Escalante A, Villegas J, Wacher C, García Garibay M, Farres A. Activity of the enzymes involved in the synthesis of exopolysaccharide precursors in an overproducing mutant ropy strain of Streptococcus thermophilus. FEMS Microbiol Lett. 2002;209:289-93 pubmed
    ..The observed variations among strains in the enzyme activities that were analysed in relation to EPS production suggest their involvement in the synthesis of sugar-nucleotide EPS precursors. ..
  7. Gajewska J, Ambroszkiewicz J, Radomyska B, Laskowska Klita T. Bone turnover markers in prepubertal children with classical galactosemia. Indian J Gastroenterol. 2006;25:221-2 pubmed
  8. Wehrli S, Reynolds R, Segal S. Evidence for function of UDP galactose pyrophosphorylase in mice with absent galactose-1-phosphate uridyltransferase. Mol Genet Metab. 2007;91:191-4 pubmed
    ..The finding is consistent with the function of UDP galactose pyrophosphorylase as an alternate pathway of galactose metabolism. ..
  9. Klipstein S, Bhagavath B, Topipat C, Sasur L, Reindollar R, Gray M. The N314D polymorphism of the GALT gene is not associated with congenital absence of the uterus and vagina. Mol Hum Reprod. 2003;9:171-4 pubmed
    ..32). It is unlikely that either maternal or fetal GALT enzyme activity could affect paramesonephric duct development, because neither galactosaemic subjects nor their children have an increased incidence of uterine anomalies. ..
  10. Henderson H, Leisegang F, Brown R, Eley B. The clinical and molecular spectrum of galactosemia in patients from the Cape Town region of South Africa. BMC Pediatr. 2002;2:7 pubmed
    ..Also, carrier frequency data predict a galactosemia incidence of approximately 1/14 400 for black newborns in the Cape Metropole, which is much higher than the current detection rate. It is thus likely that many patients go undetected. ..
  11. Reichardt J, Packman S, Woo S. Molecular characterization of two galactosemia mutations: correlation of mutations with highly conserved domains in galactose-1-phosphate uridyl transferase. Am J Hum Genet. 1991;49:860-7 pubmed
    ..Our data provide further evidence for the heterogeneity of galactosemia at the molecular level, heterogeneity which might be related to the variable clinical outcome observed in this disorder. ..
  12. Ko D, Chang H, Song S, Park K, Kim J, Kim M, et al. Molecular and biochemical characterization of the GALT gene in Korean patients with galactose-1-phosphate uridyltransferase deficiency. Clin Chim Acta. 2010;411:1506-10 pubmed publisher
    ..The genetic constitution of the GALT gene is responsible for galactosemia in the Korean population. ..
  13. Coffee B, Hjelm L, DeLorenzo A, Courtney E, Yu C, Muralidharan K. Characterization of an unusual deletion of the galactose-1-phosphate uridyl transferase (GALT) gene. Genet Med. 2006;8:635-40 pubmed
    ..Many of the individuals carrying the allele were of Ashkenazi Jewish ancestry suggesting that the deletion may be a common cause of galactosemia in that population. ..
  14. Linster C, Clarke S. L-Ascorbate biosynthesis in higher plants: the role of VTC2. Trends Plant Sci. 2008;13:567-73 pubmed publisher
    ..We hypothesize that regulation of L-ascorbate biosynthesis might occur at more than one step and warrants further investigation to allow for the manipulation of vitamin C levels in plants. ..
  15. Endo T, Koizumi S, Tabata K, Kakita S, Ozaki A. Large-scale production of N-acetyllactosamine through bacterial coupling. Carbohydr Res. 1999;316:179-83 pubmed
    ..N-Acetyllactosamine was accumulated at 279 mM (107 g L-1) after a 38 h reaction (2.5 L in volume) starting from orotic acid, D-galactose, and 2-acetamido-2-deoxy-D-glucose. ..
  16. Seyrantepe V, Ozguc M, Coskun T, Ozalp I, Reichardt J. Identification of mutations in the galactose-1-phosphate uridyltransferase (GALT) gene in 16 Turkish patients with galactosemia, including a novel mutation of F294Y. Mutation in brief no. 235. Online. Hum Mutat. 1999;13:339 pubmed
  17. Geeganage S, Ling V, Frey P. Roles of two conserved amino acid residues in the active site of galactose-1-phosphate uridylyltransferase: an essential serine and a nonessential cysteine. Biochemistry. 2000;39:5397-404 pubmed
    ..Ser 161 is most likely involved in donating a hydrogen bond to the beta-phosphoryl group of a substrate, thereby providing proper orientation for nucleophilic catalysis. ..
  18. Kushner R, Ryan E, Sefton J, Sanders R, Lucioni P, Moberg K, et al. A Drosophila melanogaster model of classic galactosemia. Dis Model Mech. 2010;3:618-27 pubmed publisher
    ..Using this new Drosophila model, we have begun to dissect the timing, extent and mechanism(s) of galactose sensitivity in the absence of GALT activity. ..
  19. Milánkovics I, Schuler A, Kamory E, Csokay B, Fodor F, Somogyi C, et al. Molecular and clinical analysis of patients with classic and Duarte galactosemia in western Hungary. Wien Klin Wochenschr. 2010;122:95-102 pubmed publisher
    ..The most serious clinical phenotypes in our population were associated with mutations p. Q188R, p.K285N, p.X380R, p.S297P, p.M142K, p.R.204X, p.Q169K and p.R407P, but manifestations depend on other genetic and environmental factors. ..
  20. Vaillancourt K, Moineau S, Frenette M, Lessard C, Vadeboncoeur C. Galactose and lactose genes from the galactose-positive bacterium Streptococcus salivarius and the phylogenetically related galactose-negative bacterium Streptococcus thermophilus: organization, sequence, transcription, and activity of the gal gene p. J Bacteriol. 2002;184:785-93 pubmed
    ..thermophilus galK differed from that of S. salivarius by two nucleotides, suggesting that the S. thermophilus galK gene might be poorly translated. This was confirmed by measurements of enzyme activities. ..
  21. Lima C, D Amico K, Naday I, Rosenbaum G, Westbrook E, Hendrickson W. MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family. Structure. 1997;5:763-74 pubmed
    ..A structural comparison of FHIT with PKCI and galactose-1-phosphate uridylyltransferase (GaIT) reveals additional implications for the structural and functional evolution of the ubiquitous HIT family of proteins. ..
  22. Brenner C. Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases. Biochemistry. 2002;41:9003-14 pubmed
  23. Kumar K, Rao K, Vedula S, Kanakavalli M, Vaddamani P, Deendayal M, et al. Screening of the galactose-1-phosphate uridyltransferase gene in Indian women with ovarian failure. Reprod Biomed Online. 2005;11:444-8 pubmed
  24. Torino M, Mozzi F, Font de Valdez G. Exopolysaccharide biosynthesis by Lactobacillus helveticus ATCC 15807. Appl Microbiol Biotechnol. 2005;68:259-65 pubmed
  25. Henderson J, Wells L, Fridovich Keil J. Covalent heterogeneity of the human enzyme galactose-1-phosphate uridylyltransferase. J Biol Chem. 2000;275:30088-91 pubmed
    ..Together, these data suggest that uridylylated hGALT comprises a significant fraction of the total GALT enzyme pool in normal human cells and that three of the most common patient mutations do not disrupt this distribution. ..
  26. Reichardt J. Genetic basis of galactosemia. Hum Mutat. 1992;1:190-6 pubmed
    ..In contrast, all protein polymorphisms alter variable amino acids which presumably are not important for the enzyme's function. ..
  27. Carney A, Sanders R, Garza K, McGaha L, Bean L, Coffee B, et al. Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase. Hum Mol Genet. 2009;18:1624-32 pubmed publisher
  28. Heidenreich R, Mallee J, Segal S. Rat galactose-1-phosphate uridyltransferase coding sequence, transcription start site and genomic organization. DNA Seq. 1993;3:311-8 pubmed
    ..The derived rat amino acid sequence is 90% identical to the human sequence. The isolation of rat GALT genomic sequence will facilitate future investigations of the regulation of expression of the rat GALT gene. ..
  29. Ninfali P, Bresolin N, Dallapiccola B, Novelli G. Molecular basis of galactose-1-phosphate uridyltransferase deficiency involving skeletal muscle. J Neurol. 1996;243:102-3 pubmed
  30. Kozak L, Francova H, Fajkusova L, Pijackova A, Macku J, Stastna S, et al. Mutation analysis of the GALT gene in Czech and Slovak galactosemia populations: identification of six novel mutations, including a stop codon mutation (X380R). Hum Mutat. 2000;15:206 pubmed
    ..In summary, galactosemia is a heterogeneous disorder at the molecular level, and mutation N314D, appears to be an ancient genetic variant of the GALT gene. Hum Mutat 15:206, 2000. ..
  31. Zondervan K, Cardon L, Kennedy S. Development of a Web site for the genetic epidemiology of endometriosis. Fertil Steril. 2002;78:777-81 pubmed
    ..This Web site should provide a useful information tool for the endometriosis researcher. We encourage researchers worldwide to use it, contribute to it, and share their knowledge about the condition. ..
  32. Greber Platzer S, Guldberg P, Scheibenreiter S, Item C, Schuller E, Patel N, et al. Molecular heterogeneity of classical and Duarte galactosemia: mutation analysis by denaturing gradient gel electrophoresis. Hum Mutat. 1997;10:49-57 pubmed
    ..We conclude that the mutations causing galactosemia are highly heterogeneous and that K285N is a second common galactosemia mutation in our population. ..
  33. Berry G, Leslie N, Reynolds R, Yager C, Segal S. Evidence for alternate galactose oxidation in a patient with deletion of the galactose-1-phosphate uridyltransferase gene. Mol Genet Metab. 2001;72:316-21 pubmed
    ..Further knowledge of this alternate galactose oxidative route and its regulation may aid in formulating new strategies for the treatment of galactosemia. ..
  34. Ross K, Davis C, Fridovich Keil J. Differential roles of the Leloir pathway enzymes and metabolites in defining galactose sensitivity in yeast. Mol Genet Metab. 2004;83:103-16 pubmed
    ..These results both confirm and significantly extend prior knowledge of galactose metabolism in yeast, and set the stage for future studies into the mediators and mechanism of Leloir-impaired galactose sensitivity in eukaryotes. ..
  35. Elsas L, Lai K. The molecular biology of galactosemia. Genet Med. 1998;1:40-8 pubmed
    ..In this review, we discuss the structural biology of these mutations as they affect both the GALT enzyme and patient outcome. ..
  36. Muralidharan K, Zhang W. Molecular detection of galactosemia mutations by PCR-ELISA. Methods Mol Biol. 2003;217:111-8 pubmed
  37. Barbouth D, Slepak T, Klapper H, Lai K, Elsas L. Prevention of a molecular misdiagnosis in galactosemia. Genet Med. 2006;8:178-82 pubmed
    ..Since a deletion of the GALT gene is a common mutation causing galactosemia among Ashkenazim Jewish families, this deletion should be suspected and tested for by genomic hybridization or by using primers specific for the 5 kb deletion. ..
  38. Segal S. Of mice and men: galactosemia. Mol Genet Metab. 2006;89:401-2 pubmed
  39. Wedekind J, Frey P, Rayment I. Three-dimensional structure of galactose-1-phosphate uridylyltransferase from Escherichia coli at 1.8 A resolution. Biochemistry. 1995;34:11049-61 pubmed
    ..Several of the latter residues have been implicated in human galactosemia. The present structure explains the deleterious effects of many of those mutations. ..
  40. Karas Kuzelicki N, Pfeifer V, Lukac Bajalo J. Synergistic effect of high lactase activity genotype and galactose-1-phosphate uridyl transferase (GALT) mutations on idiopathic presenile cataract formation. Clin Biochem. 2008;41:869-74 pubmed publisher
    ..High lactase activity genotypes and mutations in galactose-1-phosphate uridyl transferase have a synergistic effect on presenile cataract formation. ..
  41. Heidenreich R, Mallee J, Rogers S, Segal S. Developmental and tissue-specific modulation of rat galactose-1-phosphate uridyltransferase steady state messenger RNA and specific activity levels. Pediatr Res. 1993;34:416-9 pubmed
    ..These findings suggest that genetic regulation is important in the variable expression of GALT tissue sp act. ..
  42. Reichardt J, Novelli G, Dallapiccola B. Molecular characterization of the H319Q galactosemia mutation. Hum Mol Genet. 1993;2:325-6 pubmed
  43. Freer D, Ficicioglu C, Finegold D. Newborn screening for galactosemia: a review of 5 years of data and audit of a revised reporting approach. Clin Chem. 2010;56:437-44 pubmed publisher
    ..665 mmol/L (> or = 30 mg/dL) for urgent notification/referral dramatically reduces false positives and unnecessary follow-up, thereby reducing the stress on healthcare resources. ..
  44. Nishimoto M, Kitaoka M. One-pot enzymatic production of beta-D-galactopyranosyl-(1-->3)-2-acetamido-2-deoxy-D-galactose (galacto-N-biose) from sucrose and 2-acetamido-2-deoxy-D-galactose (N-acetylgalactosamine). Carbohydr Res. 2009;344:2573-6 pubmed publisher
    ..2007, 71, 2101-2104]. The reaction yield of GNB was 88% from GalNAc. GNB was isolated from the reaction mixture by crystallization after yeast treatment to obtain approximately 45 g of GNB in 95% purity from a 280-mL reaction mixture. ..
  45. Slepak T, Tang M, Slepak V, Lai K. Involvement of endoplasmic reticulum stress in a novel Classic Galactosemia model. Mol Genet Metab. 2007;92:78-87 pubmed
  46. Cozen W, Peters R, Reichardt J, Ng W, Felix J, Wan P, et al. Galactose-1-phosphate uridyl transferase (GALT) genotype and phenotype, galactose consumption, and the risk of borderline and invasive ovarian cancer (United States). Cancer Causes Control. 2002;13:113-20 pubmed
    ..More data are needed if this latter suggestion is to be definitively addressed. ..
  47. Ohtake A, Amemiya S. [Galactosemia]. Nihon Rinsho. 2006;Suppl 3:215-9 pubmed
  48. Mirzajani F, Mirfakhraie R, Nabati F, Tabatabaei N, Talachian E, Houshmand M. The first study of galactose-1-phosphate uridyl transferase mutations in Iranian galactosemia patients. Clin Biochem. 2006;39:697-9 pubmed
    ..1%. The allelic frequencies for S135L, Y209S, A320T, and K285N were found to be 7.1%, 7.1%, 7.1%, and 3.57% respectively. Our results show that galactosemia is a heterogeneous disorder at the molecular level among the Iranian population. ..
  49. Di Blasio A, Di Francesco S, Abbiati A, Vigano P. Genetics of endometriosis. Minerva Ginecol. 2005;57:225-36 pubmed
  50. Antshel K, Epstein I, Waisbren S. Cognitive strengths and weaknesses in children and adolescents homozygous for the galactosemia Q188R mutation: a descriptive study. Neuropsychology. 2004;18:658-64 pubmed
    ..Cognitive complications in galactosemia appear to emerge even in well-treated children...
  51. Thoden J, Ruzicka F, Frey P, Rayment I, Holden H. Structural analysis of the H166G site-directed mutant of galactose-1-phosphate uridylyltransferase complexed with either UDP-glucose or UDP-galactose: detailed description of the nucleotide sugar binding site. Biochemistry. 1997;36:1212-22 pubmed
    ..As such, the mutant protein structures presented here represent valid models for understanding substrate recognition and binding in the native galactose-1-phosphate uridylyltransferase. ..
  52. Mlinar B, Gersak K, Karas N, Zitnik I, Battelino T, Lukac Bajalo J. Galactose-1-phosphate uridyl transferase gene mutations in women with premature ovarian failure. Fertil Steril. 2005;84:253-5 pubmed
    ..No association of the mutations with POF was found. ..
  53. Tyfield L. Galactosaemia and allelic variation at the galactose-1-phosphate uridyltransferase gene: a complex relationship between genotype and phenotype. Eur J Pediatr. 2000;159 Suppl 3:S204-7 pubmed
    ..However, clinical galactosaemia is a complex trait in which multiple developmental and metabolic pathways are involved. Ultimately the phenotype is beyond the control of the single gene itself. ..