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Metabolic heritage mapping: heterogenous pools of cytoplasmic nucleotide sugars are selectively utilized by various glycosyltransferases

Paulina Sosicka, Bobby G. Ng, Lauren E. Pepi, Asif Shajahan, Maurice Wong, David A. Scott, Kenjiroo Matsumoto, Zhi-Jie Xia, Carlito B. Lebrilla, Robert S. Haltiwanger, Parastoo Azadi, Hudson H. Freeze
doi: https://doi.org/10.1101/2021.11.03.467160
Paulina Sosicka
1Human Genetics Program, Sanford Burnham Prebys, La Jolla, California
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Bobby G. Ng
1Human Genetics Program, Sanford Burnham Prebys, La Jolla, California
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Lauren E. Pepi
2Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia
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Asif Shajahan
2Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia
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Maurice Wong
3Department of Chemistry, University of California Davis, Davis, California
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David A. Scott
4Cancer Center, Sanford Burnham Prebys, La Jolla, California
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Kenjiroo Matsumoto
2Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia
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Zhi-Jie Xia
1Human Genetics Program, Sanford Burnham Prebys, La Jolla, California
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Carlito B. Lebrilla
3Department of Chemistry, University of California Davis, Davis, California
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Robert S. Haltiwanger
2Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia
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Parastoo Azadi
2Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia
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Hudson H. Freeze
1Human Genetics Program, Sanford Burnham Prebys, La Jolla, California
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  • For correspondence: hudson@sbpdiscovery.org
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ABSTRACT

Biosynthesis of macromolecules requires precursors such as sugars or amino acids, originating from exogenous/dietary sources, reutilization/salvage of degraded molecules or de novo synthesis. Since these sources are assumed to contribute to one homogenous pool, their individual contributions are often overlooked. Protein glycosylation uses monosaccharides from all the above sources to produce nucleotide sugars required to assemble hundreds of distinct glycans. Here we demonstrate that cells identify the origin/heritage of the monosaccharide, fucose, for glycosylation. We measured the contribution of GDP-fucose from each of these sources for glycan synthesis and found that different fucosyltransferases, individual glycoproteins, and linkage-specific fucose residues identify and select different GDP-fucose pools dependent on their heritage. This supports the hypothesis that GDP-fucose exists in multiple, distinct pools, not as a single homogenous pool. The selection is tightly regulated since the overall pool size remains constant. We present novel perspectives on monosaccharide metabolism, which may have general applicability.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 04, 2021.
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Metabolic heritage mapping: heterogenous pools of cytoplasmic nucleotide sugars are selectively utilized by various glycosyltransferases
Paulina Sosicka, Bobby G. Ng, Lauren E. Pepi, Asif Shajahan, Maurice Wong, David A. Scott, Kenjiroo Matsumoto, Zhi-Jie Xia, Carlito B. Lebrilla, Robert S. Haltiwanger, Parastoo Azadi, Hudson H. Freeze
bioRxiv 2021.11.03.467160; doi: https://doi.org/10.1101/2021.11.03.467160
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Metabolic heritage mapping: heterogenous pools of cytoplasmic nucleotide sugars are selectively utilized by various glycosyltransferases
Paulina Sosicka, Bobby G. Ng, Lauren E. Pepi, Asif Shajahan, Maurice Wong, David A. Scott, Kenjiroo Matsumoto, Zhi-Jie Xia, Carlito B. Lebrilla, Robert S. Haltiwanger, Parastoo Azadi, Hudson H. Freeze
bioRxiv 2021.11.03.467160; doi: https://doi.org/10.1101/2021.11.03.467160

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