The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

GLA  -  galactosidase, alpha

Homo sapiens

Synonyms: Alpha-D-galactosidase A, Alpha-D-galactoside galactohydrolase, Alpha-galactosidase A, GALA, Melibiase
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of GLA


High impact information on GLA

  • It consists of a single chain of 46-50 amino acids, according to the species, and contains three vitamin K-dependent gamma-carboxyglutamic acid residues (GLA), involved in its binding to calcium and hydroxylapatite [6].
  • Fabry disease is an X-linked inborn error of metabolism resulting from the deficient activity of the lysosomal hydrolase, alpha-galactosidase A (alpha-Gal A; alpha-D-galactoside galactohydrolase, EC [7].
  • These results strongly suggest that there is coordinate reactivation of GLA and HPRT [8].
  • The N-terminal amino acid sequences of light chain GLA extracted from the renal biopsy and light chain CHO from myocardial tissue were each identical to the respective light chains isolated from the urines and to the V-region amino acid sequences translated from the cloned cDNAs obtained from bone marrow cells [9].
  • These results indicate that determinants in both the GLA and the first EGF domain contribute to the specific binding of Factor IX to the endothelial cell surface and that structural requirements for Factor IX-cell surface interaction are distinct from those for Factor IX binding to lipids [10].

Chemical compound and disease context of GLA


Biological context of GLA

  • Using pulsed field gel electrophoresis we have constructed a long-range restriction map that shows that the alpha-galactosidase A gene (GLA) and DXS178 lie no more than 140 kb apart on a stretch of DNA containing a number of putative CpG islands [15].
  • We have produced physical maps of the proximal part of Xq22, containing the Bruton's tyrosine kinase (BTK) and alpha-galactosidase A (GLA) gene loci, using long range physical mapping techniques and yeast artificial chromosomes (YACs) [16].
  • Study subjects were obligate heterozygotes for mutations in GLA [17].
  • The ratios of GUSB to GLA were similar at all phases of cell growth, but the level of GUSB expression from the double copy vector was several-fold higher than from the single copy vector [18].
  • The age-score trendline of Fabry females who had a predominantly inactivated X-chromosome bearing a wild-type GLA allele (10 of 38 females) was markedly steeper than in the rest of the cohort [19].

Anatomical context of GLA

  • In this study, the contributions of the gamma-carboxyglutamic acid-containing (GLA) and growth factor domains to the finding of Factor IX to the endothelium were assessed [10].
  • The dose-dependent effect of dietary supplemented gamma-linolenic acid (GLA, 18:3n-6)-enriched borage oil (Bor) and black-currant oil on the ability of calcium ionophore-activated human polymorphonuclear neutrophils (PMN) to generate leukotriene B4 (LTB4) was investigated in adult healthy human volunteers [20].
  • We examined how y-linolenic acid (GLA; 18: 3n-6), the most promising UFA in the treatment of human tumors, affects the effectiveness of the lipophilic drug vinorelbine (VNR) on human breast carcinoma cell lines [21].
  • The n-6 PUFA, GLA, dihomo-gamma-linolenic acid (20:3n-6, DHLA) and AA, and certain oxidative metabolites of AA can also induce T-regulatory cell activity, e.g., transforming growth factor (TGF)-beta-producing T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha production [22].
  • Activation by synthetic lipid A subunit analogues (GLA compounds) of tumoricidal properties in human blood monocytes [5].

Associations of GLA with chemical compounds

  • There was a significant increase (P less than 0.01) in the GLU/GLA ratio after warfarin ingestion in the normal subjects [23].
  • Significant (P less than 0.05) elevation of dihomo-gamma-linolenic acid (DGLA, 20:3n-6), an elongation product of GLA, was revealed in PMN phospholipids after ingestion of either 0.48 or 1.5 g GLA-enriched oil/d. This elevation of DGLA in the PMN phospholipids paralleled the decreased capacity of calcium ionophore-activated PMN to generate LTB4 [20].
  • Osteocalcin or bone gamma-glutamic acid-containing protein (GLA protein) was isolated from human bone and used to develop a homologous radioimmunoassay of human osteocalcin [24].
  • In addition, plasma levels of calcium, phosphate, alkaline phosphatase and serum levels of oesteocalcin (GLA) have been assayed, both before and after 3 months of starting either tamoxifen or placebo treatment [25].
  • For comparison, the effects of other UFAs were examined on VNR chemosensitivity: GLA was the most potent at enhancing VNR activity, followed by docosahexaenoic acid (22: 6n-3), eicosapentaenoic acid (20: 5n-3) and alpha-linolenic acid (18: 3n-3), whereas linoleic acid (18: 2n-6) and arachidonic acid (20: 4n-6) did not increase VNR chemosensitivity [21].

Regulatory relationships of GLA

  • Therefore, our results show that the fatty acid GLA enhances the cytotoxicity of docetaxel in human breast cancer cells by mechanisms other than lipoperoxidation, and that GLA-induced transcriptional repression of HER-2/neu oncogene might be one component of the mechanisms of this interaction [26].

Other interactions of GLA

  • Chromosome and isozyme analysis of human chromosomes and gene products in the hybrids localized GLA to Xpter----q22, HEXB to 5q13----qter, in both cases narrowing the regional assignments, and ARSB to 5pter----q13 [27].
  • METHODS AND RESULTS: Genetic cause was investigated in 15 probands with apical hypertrophy by DNA sequence analyses of 9 sarcomere protein genes and 3 other genes (GLA, PRKAG2, and LAMP2) implicated in idiopathic cardiac hypertrophy [28].
  • The specific activity of GUSB and a control normal lysosomal enzyme, alpha-galactosidase (GLA), were higher in normal and in vector-corrected cells from confluent cultures than in subconfluent dividing cells [18].
  • In 31 children and adolescents with cystic fibrosis (CF), whose bone mineral density (BMD) was determined at the level of the lumbar spine, serum bone gamma-carboxyglutamine acid (GLA) protein (BGP) was measured [29].
  • Fibronectin was shown to compete with GLA, confirming that binding occurs through this domain [30].

Analytical, diagnostic and therapeutic context of GLA

  • Using an ELISA technique we studied the ability of pro and active forms of gelatinases A and B (GLA and GLB) to bind to matrix components and the contribution made by the different enzyme domains [30].
  • We report a rapid, sensitive and reproducible method to measure free gamma-carboxyglutamic acid (GLA) in serum using precolumn derivatization with O-phthalaldehyde, reversed-phase chromatography and deproteinization of serum by ultrafiltration [31].
  • Further experiments showed that GLA markedly decreased the expression of p185HER-2/neu oncoprotein in MCF-7 breast cancer cells (</=85%), and RT-PCR analysis revealed that HER-2/neu mRNA was selectively decreased in a concentration-dependent manner following GLA treatment [26].
  • Flow cytometric and immunoblotting analyses demonstrated that GLA treatment substantially reduced Her-2/neu protein levels in the Her-2/neu-overexpressing cell lines BT-474, SK-Br3, and MDA-MB-453 (breast cancer), SK-OV3 (ovarian cancer), and NCI-N87 (gastrointestinal tumor derived) [32].
  • The results of two major randomized, double-blind, placebo-controlled clinical trials and open-label extensions have shown that replacement of the deficient enzyme with either of two preparations of recombinant human alpha-galactosidase A, agalsidase-alfa, and agalsidase-beta is safe [33].


  1. Fabry disease: identification of novel alpha-galactosidase A mutations and molecular carrier detection by use of fluorescent chemical cleavage of mismatches. Germain, D.P., Poenaru, L. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  2. Fabry disease: 20 novel GLA mutations in 35 families. Blaydon, D., Hill, J., Winchester, B. Hum. Mutat. (2001) [Pubmed]
  3. Single-gene mutations and increased left ventricular wall thickness in the community: the Framingham Heart Study. Morita, H., Larson, M.G., Barr, S.C., Vasan, R.S., O'Donnell, C.J., Hirschhorn, J.N., Levy, D., Corey, D., Seidman, C.E., Seidman, J.G., Benjamin, E.J. Circulation (2006) [Pubmed]
  4. Treatment of diabetic neuropathy with gamma-linolenic acid. The gamma-Linolenic Acid Multicenter Trial Group. Keen, H., Payan, J., Allawi, J., Walker, J., Jamal, G.A., Weir, A.I., Henderson, L.M., Bissessar, E.A., Watkins, P.J., Sampson, M. Diabetes Care (1993) [Pubmed]
  5. Activation by synthetic lipid A subunit analogues (GLA compounds) of tumoricidal properties in human blood monocytes. Maeda, H., Saiki, I., Yamamoto, N., Takahashi, T., Sekiguchi, S., Kiso, M., Hasegawa, A., Azuma, I. Vaccine (1990) [Pubmed]
  6. Osteocalcin induces chemotaxis, secretion of matrix proteins, and calcium-mediated intracellular signaling in human osteoclast-like cells. Chenu, C., Colucci, S., Grano, M., Zigrino, P., Barattolo, R., Zambonin, G., Baldini, N., Vergnaud, P., Delmas, P.D., Zallone, A.Z. J. Cell Biol. (1994) [Pubmed]
  7. Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A. Calhoun, D.H., Bishop, D.F., Bernstein, H.S., Quinn, M., Hantzopoulos, P., Desnick, R.J. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  8. Frequency of reactivation and variability in expression of X-linked enzyme loci. Mohandas, T., Sparkes, R.S., Bishop, D.F., Desnick, R.J., Shapiro, L.J. Am. J. Hum. Genet. (1984) [Pubmed]
  9. Somatic mutations of the L12a gene in V-kappa(1) light chain deposition disease: potential effects on aberrant protein conformation and deposition. Vidal, R., Goñi, F., Stevens, F., Aucouturier, P., Kumar, A., Frangione, B., Ghiso, J., Gallo, G. Am. J. Pathol. (1999) [Pubmed]
  10. Structural determinants of the factor IX molecule mediating interaction with the endothelial cell binding site are distinct from those involved in phospholipid binding. Ryan, J., Wolitzky, B., Heimer, E., Lambrose, T., Felix, A., Tam, J.P., Huang, L.H., Nawroth, P., Wilner, G., Kisiel, W. J. Biol. Chem. (1989) [Pubmed]
  11. Gamma-carboxyglutamic acid in urine of newborn infants. Sann, L., Leclercq, M., Fouillit, M., Chapuis, M.C., Bruyère, A. Clin. Chim. Acta (1984) [Pubmed]
  12. The use of gamma-linolenic acid in diabetic neuropathy. Horrobin, D.F. Agents Actions Suppl. (1992) [Pubmed]
  13. Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibroblasts and Fabry mice. Sakuraba, H., Murata-Ohsawa, M., Kawashima, I., Tajima, Y., Kotani, M., Ohshima, T., Chiba, Y., Takashiba, M., Jigami, Y., Fukushige, T., Kanzaki, T., Itoh, K. J. Hum. Genet. (2006) [Pubmed]
  14. Enzyme replacement therapy in Fabry disease. Brady, R.O., Murray, G.J., Moore, D.F., Schiffmann, R. J. Inherit. Metab. Dis. (2001) [Pubmed]
  15. Physical mapping shows close linkage between the alpha-galactosidase A gene (GLA) and the DXS178 locus. Vetrie, D., Bentley, D., Bobrow, M., Harris, A. Hum. Genet. (1993) [Pubmed]
  16. Physical mapping in the region of the Bruton's tyrosine kinase and alpha-galactosidase A gene loci in proximal Xq22. Sweatman, A.K., Bradley, L.A., Lovering, R.C., O'Reilly, M.A., Levinsky, R.J., Kinnon, C. Hum. Genet. (1994) [Pubmed]
  17. Comparison of health-related quality of life between heterozygous women with Fabry disease, a healthy control population, and patients with other chronic disease. Street, N.J., Yi, M.S., Bailey, L.A., Hopkin, R.J. Genet. Med. (2006) [Pubmed]
  18. High level expression and export of beta-glucuronidase from murine mucopolysaccharidosis VII cells corrected by a double-copy retrovirus vector. Wolfe, J.H., Kyle, J.W., Sands, M.S., Sly, W.S., Markowitz, D.G., Parente, M.K. Gene Ther. (1995) [Pubmed]
  19. Relationship between X-inactivation and clinical involvement in Fabry heterozygotes. Eleven novel mutations in the alpha-galactosidase A gene in the Czech and Slovak population. Dobrovolny, R., Dvorakova, L., Ledvinova, J., Magage, S., Bultas, J., Lubanda, J.C., Elleder, M., Karetova, D., Pavlikova, M., Hrebicek, M. J. Mol. Med. (2005) [Pubmed]
  20. Dose-response effects of dietary gamma-linolenic acid-enriched oils on human polymorphonuclear-neutrophil biosynthesis of leukotriene B4. Ziboh, V.A., Fletcher, M.P. Am. J. Clin. Nutr. (1992) [Pubmed]
  21. Synergistic interaction between vinorelbine and gamma-linolenic acid in breast cancer cells. Menéndez, J.A., Ropero, S., del Barbacid, M.M., Montero, S., Solanas, M., Escrich, E., Cortés-Funes, H., Colomer, R. Breast Cancer Res. Treat. (2002) [Pubmed]
  22. Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3. Harbige, L.S. Lipids (2003) [Pubmed]
  23. Impaired carboxylation of osteocalcin in warfarin-treated patients. Menon, R.K., Gill, D.S., Thomas, M., Kernoff, P.B., Dandona, P. J. Clin. Endocrinol. Metab. (1987) [Pubmed]
  24. Homologous radioimmunoassay of human osteocalcin. Bouillon, R., Vanderschueren, D., Van Herck, E., Nielsen, H.K., Bex, M., Heyns, W., Van Baelen, H. Clin. Chem. (1992) [Pubmed]
  25. Bone mineral content of women receiving tamoxifen for mastalgia. Fentiman, I.S., Caleffi, M., Rodin, A., Murby, B., Fogelman, I. Br. J. Cancer (1989) [Pubmed]
  26. Omega-6 polyunsaturated fatty acid gamma-linolenic acid (18:3n-6) enhances docetaxel (Taxotere) cytotoxicity in human breast carcinoma cells: Relationship to lipid peroxidation and HER-2/neu expression. Menendez, J.A., Ropero, S., Lupu, R., Colomer, R. Oncol. Rep. (2004) [Pubmed]
  27. Regional localization of alpha-galactosidase (GLA) to Xpter----q22, hexosaminidase B (HEXB) to 5q13----qter, and arylsulfatase B (ARSB) to 5pter----q13. Fox, M.F., DuToit, D.L., Warnich, L., Retief, A.E. Cytogenet. Cell Genet. (1984) [Pubmed]
  28. Gene mutations in apical hypertrophic cardiomyopathy. Arad, M., Penas-Lado, M., Monserrat, L., Maron, B.J., Sherrid, M., Ho, C.Y., Barr, S., Karim, A., Olson, T.M., Kamisago, M., Seidman, J.G., Seidman, C.E. Circulation (2005) [Pubmed]
  29. Low serum bone gamma-carboxyglutamic acid protein concentrations in patients with cystic fibrosis: correlation with hormonal parameters and bone mineral density. De Schepper, J., Smitz, J., Dab, I., Piepsz, A., Jonckheer, M., Bergmann, P. Horm. Res. (1993) [Pubmed]
  30. Binding of gelatinases A and B to type-I collagen and other matrix components. Allan, J.A., Docherty, A.J., Barker, P.J., Huskisson, N.S., Reynolds, J.J., Murphy, G. Biochem. J. (1995) [Pubmed]
  31. Evidence that free gamma carboxyglutamic acid circulates in serum. Fournier, B., Gineyts, E., Delmas, P.D. Clin. Chim. Acta (1989) [Pubmed]
  32. Effect of gamma-linolenic acid on the transcriptional activity of the Her-2/neu (erbB-2) oncogene. Menendez, J.A., Vellon, L., Colomer, R., Lupu, R. J. Natl. Cancer Inst. (2005) [Pubmed]
  33. Enzyme replacement therapy of Fabry disease. Clarke, J.T., Iwanochko, R.M. Mol. Neurobiol. (2005) [Pubmed]
WikiGenes - Universities