Hypoxic regulation of glycosylation via the N-acetylglucosamine cycle

Ken Shirato, Kazuki Nakajima, Hiroaki Korekane, Shinji Takamatsu, Congxiao Gao, Takashi Angata, Kazuaki Ohtsubo, Naoyuki Taniguchi

Research output: Contribution to journalReview article

36 Citations (Scopus)

Abstract

Glucose is an energy substrate, as well as the primary source of nucleotide sugars, which are utilized as donor substrates in protein glycosylation. Appropriate glycosylation is necessary to maintain the stability of protein, and is also important in the localization and trafficking of proteins. The dysregulation of glycosylation results in the development of a variety of disorders, such as cancer, diabetes mellitus and emphysema. Glycosylation is kinetically regulated by dynamically changing the portfolio of glycosyltransferases, nucleotide sugars, and nucleotide sugar transporters, which together form a part of what is currently referred to as the "Glycan cycle". An excess or a deficiency in the expression of glycosyltransferases has been shown to alter the glycosylation pattern, which subsequently leads to the onset, progression and exacerbation of a number of diseases. Furthermore, alterations in intracellular nucleotide sugar levels can also modulate glycosylation patterns. It is observed that pathological hypoxic microenvironments frequently occur in solid cancers and inflammatory foci. Hypoxic conditions dramatically change gene expression profiles, by activating hypoxia-inducible factor-1, which mediates adaptive cellular responses. Hypoxia-induced glycosyltransferases and nucleotide sugar transporters have been shown to modulate glycosylation patterns that are part of the mechanism associated with cancer metastasis. Hypoxia-inducible factor-1 also induces the expression of glucose transporters and various types of glycolytic enzymes, leading to shifts in glucose metabolic patterns. This fact strongly suggests that hypoxic conditions are an important factor in modulating various nucleotide sugar biosynthetic pathways. This review discusses some of the current thinking of how hypoxia alters glucose metabolic fluxes that can modulate cellular glycosylation patterns and consequently modify cellular functions, particularly from the standpoint of the N-acetylglucosamine cycle, a part of the "Glycan cycle".

Original languageEnglish
Pages (from-to)20-25
Number of pages6
JournalJournal of Clinical Biochemistry and Nutrition
Volume48
Issue number1
DOIs
Publication statusPublished - 01-01-2011

Fingerprint

Glycosylation
Acetylglucosamine
Sugars
Nucleotides
Glycosyltransferases
Hypoxia-Inducible Factor 1
Glucose
Polysaccharides
Neoplasms
Proteins
Facilitative Glucose Transport Proteins
Protein Stability
Biosynthetic Pathways
Emphysema
Protein Transport
Substrates
Medical problems
Transcriptome
Gene expression
Diabetes Mellitus

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Shirato, Ken ; Nakajima, Kazuki ; Korekane, Hiroaki ; Takamatsu, Shinji ; Gao, Congxiao ; Angata, Takashi ; Ohtsubo, Kazuaki ; Taniguchi, Naoyuki. / Hypoxic regulation of glycosylation via the N-acetylglucosamine cycle. In: Journal of Clinical Biochemistry and Nutrition. 2011 ; Vol. 48, No. 1. pp. 20-25.
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Shirato, K, Nakajima, K, Korekane, H, Takamatsu, S, Gao, C, Angata, T, Ohtsubo, K & Taniguchi, N 2011, 'Hypoxic regulation of glycosylation via the N-acetylglucosamine cycle', Journal of Clinical Biochemistry and Nutrition, vol. 48, no. 1, pp. 20-25. https://doi.org/10.3164/jcbn.11-015FR

Hypoxic regulation of glycosylation via the N-acetylglucosamine cycle. / Shirato, Ken; Nakajima, Kazuki; Korekane, Hiroaki; Takamatsu, Shinji; Gao, Congxiao; Angata, Takashi; Ohtsubo, Kazuaki; Taniguchi, Naoyuki.

In: Journal of Clinical Biochemistry and Nutrition, Vol. 48, No. 1, 01.01.2011, p. 20-25.

Research output: Contribution to journalReview article

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T1 - Hypoxic regulation of glycosylation via the N-acetylglucosamine cycle

AU - Shirato, Ken

AU - Nakajima, Kazuki

AU - Korekane, Hiroaki

AU - Takamatsu, Shinji

AU - Gao, Congxiao

AU - Angata, Takashi

AU - Ohtsubo, Kazuaki

AU - Taniguchi, Naoyuki

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N2 - Glucose is an energy substrate, as well as the primary source of nucleotide sugars, which are utilized as donor substrates in protein glycosylation. Appropriate glycosylation is necessary to maintain the stability of protein, and is also important in the localization and trafficking of proteins. The dysregulation of glycosylation results in the development of a variety of disorders, such as cancer, diabetes mellitus and emphysema. Glycosylation is kinetically regulated by dynamically changing the portfolio of glycosyltransferases, nucleotide sugars, and nucleotide sugar transporters, which together form a part of what is currently referred to as the "Glycan cycle". An excess or a deficiency in the expression of glycosyltransferases has been shown to alter the glycosylation pattern, which subsequently leads to the onset, progression and exacerbation of a number of diseases. Furthermore, alterations in intracellular nucleotide sugar levels can also modulate glycosylation patterns. It is observed that pathological hypoxic microenvironments frequently occur in solid cancers and inflammatory foci. Hypoxic conditions dramatically change gene expression profiles, by activating hypoxia-inducible factor-1, which mediates adaptive cellular responses. Hypoxia-induced glycosyltransferases and nucleotide sugar transporters have been shown to modulate glycosylation patterns that are part of the mechanism associated with cancer metastasis. Hypoxia-inducible factor-1 also induces the expression of glucose transporters and various types of glycolytic enzymes, leading to shifts in glucose metabolic patterns. This fact strongly suggests that hypoxic conditions are an important factor in modulating various nucleotide sugar biosynthetic pathways. This review discusses some of the current thinking of how hypoxia alters glucose metabolic fluxes that can modulate cellular glycosylation patterns and consequently modify cellular functions, particularly from the standpoint of the N-acetylglucosamine cycle, a part of the "Glycan cycle".

AB - Glucose is an energy substrate, as well as the primary source of nucleotide sugars, which are utilized as donor substrates in protein glycosylation. Appropriate glycosylation is necessary to maintain the stability of protein, and is also important in the localization and trafficking of proteins. The dysregulation of glycosylation results in the development of a variety of disorders, such as cancer, diabetes mellitus and emphysema. Glycosylation is kinetically regulated by dynamically changing the portfolio of glycosyltransferases, nucleotide sugars, and nucleotide sugar transporters, which together form a part of what is currently referred to as the "Glycan cycle". An excess or a deficiency in the expression of glycosyltransferases has been shown to alter the glycosylation pattern, which subsequently leads to the onset, progression and exacerbation of a number of diseases. Furthermore, alterations in intracellular nucleotide sugar levels can also modulate glycosylation patterns. It is observed that pathological hypoxic microenvironments frequently occur in solid cancers and inflammatory foci. Hypoxic conditions dramatically change gene expression profiles, by activating hypoxia-inducible factor-1, which mediates adaptive cellular responses. Hypoxia-induced glycosyltransferases and nucleotide sugar transporters have been shown to modulate glycosylation patterns that are part of the mechanism associated with cancer metastasis. Hypoxia-inducible factor-1 also induces the expression of glucose transporters and various types of glycolytic enzymes, leading to shifts in glucose metabolic patterns. This fact strongly suggests that hypoxic conditions are an important factor in modulating various nucleotide sugar biosynthetic pathways. This review discusses some of the current thinking of how hypoxia alters glucose metabolic fluxes that can modulate cellular glycosylation patterns and consequently modify cellular functions, particularly from the standpoint of the N-acetylglucosamine cycle, a part of the "Glycan cycle".

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