Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Aug;21(6):655-62.
doi: 10.1016/j.semcdb.2010.03.011. Epub 2010 Apr 2.

Metabolic manipulation of glycosylation disorders in humans and animal models

Hudson H Freeze  1 , Vandana Sharma
Affiliations
Review

Metabolic manipulation of glycosylation disorders in humans and animal models

Hudson H Freeze et al. Semin Cell Dev Biol. 2010 Aug.

Abstract

In the last decade, over 40 inherited human glycosylation disorders were identified. Most patients have hypomorphic, rather than null alleles. The phenotypic spectrum is broad and most of the disorders affect embryonic and early post-natal development; a few appear in adult life. Some deficiencies can be treated with simple dietary sugar (monosaccharide) supplements. Here we focus on four glycosylation disorders that have been treated with supplements in patients or in model systems, primarily the mouse. Surprisingly, small differences in the amount of exogenous sugar have a major impact on the diseases in specific cells or organs while others are unaffected. The underlying mechanisms are mostly unknown, but changes in the contributions of the de novo, salvage and dietary pathways may contribute to the beneficial outcome. Clearly, the metabolic chart is not flat; all arrows are not equally robust at all points of time and space. This metabolic perspective may help explain some of these observations and guide the development of other vertebrate models of glycosylation disorders that can respond to dietary manipulation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Biosythesis and interconversion of monosaccharides. The relative contributions of each pathway under physiological conditions are unknown. (Rectangles) Donors; (ovals) monosaccharides; (asterisks) control points; (6PG) phophogluconate; (PEP) phosphoenolpyruvate; (KDN) keto- deoxy-D-glycero-D-galactonononic acid; (Dol) dolichol.
formula image Glcformula image Manformula image Gal
formula image GlcNAcformula image GalNAcformula image Sia
formula image Fucformula image Xylformula image GlcA
See this image and copyright information in PMC

References

    1. Berry GT. Metabolic profiling. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:55–75. discussion 75–80. - PubMed
    1. Brockmann K. The expanding phenotype of GLUT1-deficiency syndrome. Brain Dev. 2009;31:545–552. - PubMed
    1. Skvorak KJ. Animal models of maple syrup urine disease. J Inherit Metab Dis. 2009;32:229–246. - PubMed
    1. Freeze HH, Elbein AD. In: Essentials of Glycobiology. 2nd ed. Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, Hart GW, Etzler ME, editors. New York: Cold Spring Harbor Laboratory Pr; 2009. pp. 47–61. - PubMed
    1. Diaz S, Varki A. Metabolic radiolabeling of animal cell glycoconjugates. In: Cooligan JE, Dunn BM, Ploegh HL, Speicher DW, Wingfield PT, editors. Curr Protoc Protein Sci. Unit 12.2. Ch 12. New Jersey: John Wiley & Sons; 2009. pp. 1–55.

Publication types

LinkOut - more resources