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. 1994 Jun 1;300(Pt 2):309–315. doi: 10.1042/bj3000309

Human glucocerebrosidase catalyses transglucosylation between glucocerebroside and retinol.

D J Vanderjagt 1, D E Fry 1, R H Glew 1
PMCID: PMC1138163  PMID: 8002933

Abstract

The basal activity of human placental glucocerebrosidase is elevated 16-fold by n-pentanol when assayed using p-nitrophenyl beta-D-glucopyranoside (pNPGlc) as the beta-glucosidase substrate. This enhancement of activity is the result of the formation of a transglucosylation product, n-pentyl beta-D-glucoside, in rate-determining competition with the hydrolytic reaction. The transglucosylation product accounts for approximately 80% of the reaction product generated in the presence of n-pentanol (0.18 M) when either glucocerebroside or pNPGlc was used as the substrate. This stimulatory effect can be increased an additional 3-fold by the inclusion of phosphatidylserine (20 micrograms/ml) or sodium taurodeoxycholate (0.3%, w/v) in the incubation medium. In the presence of retinol, glucocerebrosidase also catalyses the synthesis of a novel lipid glucoside, retinyl glucoside, when either glucocerebroside or pNPGlc serves as the substrate. The reaction product was identified as retinyl beta-D-glucoside, based on its susceptibility to hydrolysis by almond beta-D-glucosidase and the subsequent release of equimolar amounts of retinol and glucose. The rate of retinyl-beta-glucoside formation is dependent on the concentration of retinol in the incubation medium, reaching saturation at approximately 0.3 mM retinol. Retinyl beta-D-glucoside is a substrate for two broad-specificity mammalian beta-glucosidases, namely the cytosolic and membrane-associated beta-glucosidases of guinea pig liver. However, retinyl beta-D-glucoside is not hydrolysed by placental glucocerebrosidase. These data indicate that the glucocerebrosidase-catalysed transfer of glucose from glucocerebroside to natural endogenous lipid alcohols, followed by the action of a broad-specificity beta-glucosidase on the transglucosylation product, could provide mammals with an alternative pathway for the breakdown of glucocerebroside to glucose and ceramide.

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Selected References

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  1. BRADY R. O., KANFER J. N., SHAPIRO D. METABOLISM OF GLUCOCEREBROSIDES. II. EVIDENCE OF AN ENZYMATIC DEFICIENCY IN GAUCHER'S DISEASE. Biochem Biophys Res Commun. 1965 Jan 18;18:221–225. doi: 10.1016/0006-291x(65)90743-6. [DOI] [PubMed] [Google Scholar]
  2. Basu A., Glew R. H. Characterization of the phospholipid requirement of a rat liver beta-glucosidase. Biochem J. 1984 Dec 1;224(2):515–524. doi: 10.1042/bj2240515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chiao Y. B., Hoyson G. M., Peters S. P., Lee R. E., Diven W., Murphy J. V., Glew R. H. Multiple glycosidase deficiencies in a case of juvenile (type 3) Gaucher disease. Proc Natl Acad Sci U S A. 1978 May;75(5):2448–2452. doi: 10.1073/pnas.75.5.2448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Daniels L. B., Coyle P. J., Chiao Y. B., Glew R. H., Labow R. S. Purification and characterization of a cytosolic broad specificity beta-glucosidase from human liver. J Biol Chem. 1981 Dec 25;256(24):13004–13013. [PubMed] [Google Scholar]
  5. Forsyth G. W., Romero K. M., Alverson J., VanderJagt D. J., Glew R. H. Variable expression of leukocyte cytosolic broad-specificity beta-glucosidase activity. Clin Chim Acta. 1993 Jul 16;216(1-2):11–21. doi: 10.1016/0009-8981(93)90135-q. [DOI] [PubMed] [Google Scholar]
  6. Glew R. H., Basu A., LaMarco K. L., Prence E. M. Mammalian glucocerebrosidase: implications for Gaucher's disease. Lab Invest. 1988 Jan;58(1):5–25. [PubMed] [Google Scholar]
  7. Glew R. H., Peters S. P., Christopher A. R. Isolation and characterization of beta-glucosidase from the cytosol of rat kidney cortex. Biochim Biophys Acta. 1976 Jan 23;422(1):179–199. doi: 10.1016/0005-2744(76)90018-8. [DOI] [PubMed] [Google Scholar]
  8. Gopalan V., Glew R. H., Libell D. P., DePetro J. J. The dual effects of alcohols on the kinetic properties of guinea pig liver cytosolic beta-glucosidase. J Biol Chem. 1989 Sep 15;264(26):15418–15422. [PubMed] [Google Scholar]
  9. Gopalan V., Vander Jagt D. J., Libell D. P., Glew R. H. Transglucosylation as a probe of the mechanism of action of mammalian cytosolic beta-glucosidase. J Biol Chem. 1992 May 15;267(14):9629–9638. [PubMed] [Google Scholar]
  10. Grabowski G. A., Gatt S., Horowitz M. Acid beta-glucosidase: enzymology and molecular biology of Gaucher disease. Crit Rev Biochem Mol Biol. 1990;25(6):385–414. doi: 10.3109/10409239009090616. [DOI] [PubMed] [Google Scholar]
  11. LaMarco K. L., Glew R. H. Hydrolysis of a naturally occurring beta-glucoside by a broad-specificity beta-glucosidase from liver. Biochem J. 1986 Jul 15;237(2):469–476. doi: 10.1042/bj2370469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Legler G., Bieberich E. Isolation of a cytosolic beta-glucosidase from calf liver and characterization of its active site with alkyl glucosides and basic glycosyl derivatives. Arch Biochem Biophys. 1988 Jan;260(1):427–436. doi: 10.1016/0003-9861(88)90466-3. [DOI] [PubMed] [Google Scholar]
  13. Morimoto S., Kishimoto Y., Tomich J., Weiler S., Ohashi T., Barranger J. A., Kretz K. A., O'Brien J. S. Interaction of saposins, acidic lipids, and glucosylceramidase. J Biol Chem. 1990 Feb 5;265(4):1933–1937. [PubMed] [Google Scholar]
  14. Mumford R. A., Raghavan S. S., Kanfer J. N. Hydrolytic and transglucolytic activities of a partially purified calf brain beta-glucosidase. J Neurochem. 1976 Oct;27(4):943–948. doi: 10.1111/j.1471-4159.1976.tb05159.x. [DOI] [PubMed] [Google Scholar]
  15. Ockerman P. A. Identity of beta-glucosidase, beta-xylosidase and one of the beta-galactosidase activities in human liver when assayed with 4-methylumbelliferyl-beta-D-glycosides studies in cases of Gaucher's disease. Biochim Biophys Acta. 1968 Aug 6;165(1):59–62. [PubMed] [Google Scholar]
  16. Ohashi T., Hong C. M., Weiler S., Tomich J. M., Aerts J. M., Tager J. M., Barranger J. A. Characterization of human glucocerebrosidase from different mutant alleles. J Biol Chem. 1991 Feb 25;266(6):3661–3667. [PubMed] [Google Scholar]
  17. Orr J. W., Keranen L. M., Newton A. C. Reversible exposure of the pseudosubstrate domain of protein kinase C by phosphatidylserine and diacylglycerol. J Biol Chem. 1992 Aug 5;267(22):15263–15266. [PubMed] [Google Scholar]
  18. Owada M., Sakiyama T., Kitagawa T. Neuropathic Gaucher's disease with normal 4-methylumbelliferyl-beta-glucosidase activity in the liver. Pediatr Res. 1977 May;11(5):641–646. doi: 10.1203/00006450-197705000-00004. [DOI] [PubMed] [Google Scholar]
  19. Peters S. P., Lee R. E., Glew R. H. A microassay for Gaucher's disease. Clin Chim Acta. 1975 May 1;60(3):391–396. doi: 10.1016/0009-8981(75)90083-2. [DOI] [PubMed] [Google Scholar]
  20. Pócsi I., Kiss L. Kinetic studies on the broad-specificity beta-D-glucosidase from pig kidney. Biochem J. 1988 Nov 15;256(1):139–146. doi: 10.1042/bj2560139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stokes T. M., Wilson I. B. A common intermediate in the hydrolysis of -galactosides by -galactosidase from Escherichia coli. Biochemistry. 1972 Mar 14;11(6):1061–1064. doi: 10.1021/bi00756a018. [DOI] [PubMed] [Google Scholar]
  22. Umezurike G. M. Kinetic properties of -glucosidase from Botryodiplodia theobromae Pat. Biochim Biophys Acta. 1971 Oct;250(1):182–191. doi: 10.1016/0005-2744(71)90132-x. [DOI] [PubMed] [Google Scholar]
  23. Van der Groen G., Wouters-Leysen J., Yde M., De Bruyne C. K. Effects of alcohols on beta-galactosidase-catalyzed hydrolysis of n-alkyl-beta-D-galactopyranosides. Eur J Biochem. 1973 Sep 21;38(1):122–129. doi: 10.1111/j.1432-1033.1973.tb03041.x. [DOI] [PubMed] [Google Scholar]
  24. van Weely S., Brandsma M., Strijland A., Tager J. M., Aerts J. M. Demonstration of the existence of a second, non-lysosomal glucocerebrosidase that is not deficient in Gaucher disease. Biochim Biophys Acta. 1993 Mar 24;1181(1):55–62. doi: 10.1016/0925-4439(93)90090-n. [DOI] [PubMed] [Google Scholar]

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