Metabolic selection of glycosylation defects in human cells.

Abstract:

:Changes in glycosylation are often associated with disease progression, but the genetic and metabolic basis of these events is rarely understood in detail at a molecular level. We describe a metabolism-based approach to the selection of mutants in glycoconjugate biosynthesis that provides insight into regulatory mechanisms for oligosaccharide expression and metabolic flux. Unnatural intermediates are used to challenge a specific pathway, and cell surface expression of their metabolic products provides a readout of flux in that pathway and a basis for selecting genetic mutants. The approach was applied to the sialic acid metabolic pathway in human cells, yielding novel mutants with phenotypes related to the inborn metabolic defect sialuria and metastatic tumor cells.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Yarema KJ,Goon S,Bertozzi CR

doi

10.1038/89305

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

553-8

issue

6

eissn

1087-0156

issn

1546-1696

pii

89305

journal_volume

19

pub_type

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