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. 1990 Jun 15;268(3):621–625. doi: 10.1042/bj2680621

Defective glucuronic acid transport from lysosomes of infantile free sialic acid storage disease fibroblasts.

H J Blom 1, H C Andersson 1, R Seppala 1, F Tietze 1, W A Gahl 1
PMCID: PMC1131484  PMID: 2363700

Abstract

Separation by h.p.l.c. and pulsed amperometric detection were employed to measure glucuronic acid (GlcUA) and other acidic monosaccharides in fibroblasts from patients with infantile free sialic acid storage disease (ISSD) and Salla disease. These lysosomal storage disorders result from defective carrier-mediated transport of free N-acetylneuraminic acid (NeuAc) out of cellular lysosomes. Three Salla disease fibroblast strains stored approx. 0.4 nmol of free GlcUA/mg of cell protein, whereas four ISSD strains stored approx. 5 nmol GlcUA/mg (normal is undetectable). The GlcUA content of the mutant cell strains, which by differential centrifugation and Percoll gradient fractionation was localized to the lysosomes, averaged 5% of the free NeuAc content of the cells. N-Glycolylneuraminic acid (NeuGc) also accumulated in ISSD cells, but only when they were grown in the presence of fetal calf serum, which contains abundant NeuGc. No other acidic monosaccharides were detected in any of the mutant cell strains. GlcUA egress studies revealed that 56% of the initial GlcUA content was lost from normal granular fractions after 2 min at 37 degrees C. For similarly loaded ISSD granular fractions, virtually no GlcUA was lost even after 6 min. The results indicate that GlcUA is recognized and transported by the lysosomal NeuAc carrier, and that GlcUA transport is impaired in the lysosomal disorders of free NeuAc storage.

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Selected References

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  1. Aula P., Autio S., Raivio K. O., Rapola J., Thodén C. J., Koskela S. L., Yamashina I. "Salla disease": a new lysosomal storage disorder. Arch Neurol. 1979 Feb;36(2):88–94. doi: 10.1001/archneur.1979.00500380058006. [DOI] [PubMed] [Google Scholar]
  2. Bernar J., Tietze F., Kohn L. D., Bernardini I., Harper G. S., Grollman E. F., Gahl W. A. Characteristics of a lysosomal membrane transport system for tyrosine and other neutral amino acids in rat thyroid cells. J Biol Chem. 1986 Dec 25;261(36):17107–17112. [PubMed] [Google Scholar]
  3. Clements P. R., Taylor J. A., Hopwood J. J. Biochemical characterization of patients and prenatal diagnosis of sialic acid storage disease for three families. J Inherit Metab Dis. 1988;11(1):30–44. doi: 10.1007/BF01800055. [DOI] [PubMed] [Google Scholar]
  4. Docherty K., Brenchley G. V., Hales C. N. The permeability of rat liver lysosomes to sugars. Evidence for carrier-mediated facilitated diffusion. Biochem J. 1979 Feb 15;178(2):361–366. doi: 10.1042/bj1780361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gahl W. A., Bashan N., Tietze F., Bernardini I., Schulman J. D. Cystine transport is defective in isolated leukocyte lysosomes from patients with cystinosis. Science. 1982 Sep 24;217(4566):1263–1265. doi: 10.1126/science.7112129. [DOI] [PubMed] [Google Scholar]
  6. Gahl W. A. Lysosomal membrane transport in cellular nutrition. Annu Rev Nutr. 1989;9:39–61. doi: 10.1146/annurev.nu.09.070189.000351. [DOI] [PubMed] [Google Scholar]
  7. Gahl W. A., Tietze F., Bashan N., Bernardini I., Raiford D., Schulman J. D. Characteristics of cystine counter-transport in normal and cystinotic lysosome-rich leucocyte granular fractions. Biochem J. 1983 Nov 15;216(2):393–400. doi: 10.1042/bj2160393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jonas A. J., Smith M. L., Schneider J. A. ATP-dependent lysosomal cystine efflux is defective in cystinosis. J Biol Chem. 1982 Nov 25;257(22):13185–13188. [PubMed] [Google Scholar]
  9. Jonas A. J., Speller R. J., Conrad P. B., Dubinsky W. P. Transport of N-acetyl-D-glucosamine and N-acetyl-D-galactosamine by rat liver lysosomes. J Biol Chem. 1989 Mar 25;264(9):4953–4956. [PubMed] [Google Scholar]
  10. Maguire G. A., Docherty K., Hales C. N. Sugar transport in rat liver lysosomes. Direct demonstration by using labelled sugars. Biochem J. 1983 Apr 15;212(1):211–218. doi: 10.1042/bj2120211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mancini G. M., de Jonge H. R., Galjaard H., Verheijen F. W. Characterization of a proton-driven carrier for sialic acid in the lysosomal membrane. Evidence for a group-specific transport system for acidic monosaccharides. J Biol Chem. 1989 Sep 15;264(26):15247–15254. [PubMed] [Google Scholar]
  12. Muchmore E. A., Milewski M., Varki A., Diaz S. Biosynthesis of N-glycolyneuraminic acid. The primary site of hydroxylation of N-acetylneuraminic acid is the cytosolic sugar nucleotide pool. J Biol Chem. 1989 Dec 5;264(34):20216–20223. [PubMed] [Google Scholar]
  13. Paschke E., Trinkl G., Erwa W., Pavelka M., Mutz I., Roscher A. Infantile type of sialic acid storage disease with sialuria. Clin Genet. 1986 May;29(5):417–424. doi: 10.1111/j.1399-0004.1986.tb00514.x. [DOI] [PubMed] [Google Scholar]
  14. Pisoni R. L., Flickinger K. S., Thoene J. G., Christensen H. N. Characterization of carrier-mediated transport systems for small neutral amino acids in human fibroblast lysosomes. J Biol Chem. 1987 May 5;262(13):6010–6017. [PubMed] [Google Scholar]
  15. Pisoni R. L., Thoene J. G., Christensen H. N. Detection and characterization of carrier-mediated cationic amino acid transport in lysosomes of normal and cystinotic human fibroblasts. Role in therapeutic cystine removal? J Biol Chem. 1985 Apr 25;260(8):4791–4798. [PubMed] [Google Scholar]
  16. Pisoni R. L., Thoene J. G. Detection and characterization of a nucleoside transport system in human fibroblast lysosomes. J Biol Chem. 1989 Mar 25;264(9):4850–4856. [PubMed] [Google Scholar]
  17. Renlund M., Aula P., Raivio K. O., Autio S., Sainio K., Rapola J., Koskela S. L. Salla disease: a new lysosomal storage disorder with disturbed sialic acid metabolism. Neurology. 1983 Jan;33(1):57–66. doi: 10.1212/wnl.33.1.57. [DOI] [PubMed] [Google Scholar]
  18. Renlund M., Tietze F., Gahl W. A. Defective sialic acid egress from isolated fibroblast lysosomes of patients with Salla disease. Science. 1986 May 9;232(4751):759–762. doi: 10.1126/science.3961501. [DOI] [PubMed] [Google Scholar]
  19. Rosenblatt D. S., Hosack A., Matiaszuk N. V., Cooper B. A., Laframboise R. Defect in vitamin B12 release from lysosomes: newly described inborn error of vitamin B12 metabolism. Science. 1985 Jun 14;228(4705):1319–1321. doi: 10.1126/science.4001945. [DOI] [PubMed] [Google Scholar]
  20. Schauer R. Chemistry, metabolism, and biological functions of sialic acids. Adv Carbohydr Chem Biochem. 1982;40:131–234. doi: 10.1016/s0065-2318(08)60109-2. [DOI] [PubMed] [Google Scholar]
  21. Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., Klenk D. C. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
  22. Stevenson R. E., Lubinsky M., Taylor H. A., Wenger D. A., Schroer R. J., Olmstead P. M. Sialic acid storage disease with sialuria: clinical and biochemical features in the severe infantile type. Pediatrics. 1983 Oct;72(4):441–449. [PubMed] [Google Scholar]
  23. Tietze F., Kohn L. D., Kohn A. D., Bernardini I., Andersson H. C., Adamson M. D., Harper G. S., Gahl W. A. Carrier-mediated transport of monoiodotyrosine out of thyroid cell lysosomes. J Biol Chem. 1989 Mar 25;264(9):4762–4765. [PubMed] [Google Scholar]
  24. Tietze F., Seppala R., Renlund M., Hopwood J. J., Harper G. S., Thomas G. H., Gahl W. A. Defective lysosomal egress of free sialic acid (N-acetylneuraminic acid) in fibroblasts of patients with infantile free sialic acid storage disease. J Biol Chem. 1989 Sep 15;264(26):15316–15322. [PubMed] [Google Scholar]
  25. Tondeur M., Libert J., Vamos E., Van Hoof F., Thomas G. H., Strecker G. Infantile form of sialic acid storage disorder: clinical, ultrastructural, and biochemical studies in two siblings. Eur J Pediatr. 1982 Oct;139(2):142–147. doi: 10.1007/BF00441499. [DOI] [PubMed] [Google Scholar]

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