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UDP-GlcNAc 2-Epimerase/ManNAc Kinase (GNE): A Master Regulator of Sialic Acid Synthesis

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SialoGlyco Chemistry and Biology I

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 366))

Abstract

UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is the key enzyme of sialic acid biosynthesis in vertebrates. It catalyzes the first two steps of the cytosolic formation of CMP-N-acetylneuraminic acid from UDP-N-acetylglucosamine. In this review we give an overview of structure, biochemistry, and genetics of the bifunctional enzyme and its complex regulation. Furthermore, we will focus on diseases related to UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase.

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Abbreviations

ADP:

Adenosine diphosphate

ATP:

Adenosine triphosphate

AT2R:

Angiotensin 2 receptor

bp:

Basepairs

CHO:

Chinese hamster ovary

CMP:

Cytidine monophosphate

CRMP1:

Collapsin response mediator protein 1

DMRV:

Distal myopathy with rimmed vacuoles

ES cell:

Embryonic stem cell

GalNAc:

N-Acetylgalactosamine

GlcNAc:

N-Acetylglucosamine

GNE:

UDP-GlcNAc 2-epimerase/ManNAc kinase

HEK:

Human epithelial kidney

HIBM:

Hereditary inclusion body myopathy

IBM2:

Inclusion body myopathy 2

kDa:

Kilodaltons

ManNAc:

N-Acetylmannosamine

ManNGc:

N-Glycolylmannosamine

MRI:

Magnetic resonance imaging

NCAM:

Neural cell adhesion molecule

Neu5Ac:

N-Acetylneuraminic acid

Neu5Gc:

N-Glycolylneuraminic acid

PEP:

Phosphoenolpyruvate

PKC:

Protein kinase C

PLZF:

Promyelocytic leukemia zinc finger protein

PTM:

Posttranslational modification

RIF1:

Receptor interacting factor 1

ROK family:

Repressor/open reading frame/kinase protein family

SPR:

Surface plasmon resonance

STD-NMR:

Saturation-transfer difference – nuclear magnetic resonance spectroscopy

TUC family:

Toad-64/Ulip/CRMP protein family

UDP:

Uridine diphosphate

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Acknowledgments

This work was performed in partial fulfillment of the requirements for a PhD degree of T.Y., Sackler Faculty of Medicine, Tel Aviv University, Israel. This study was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA, to T.Y. and M.H. S.H. acknowledges financial support of the Bundesministerium für Bildung und Forschung and the German-Israeli Foundation for Scientific Research and Development; R.H. acknowledges support of the Deutsche Forschungsgemeinschaft.

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  1. Department of Life Sciences and Technology, Beuth Hochschule für Technik Berlin, University of Applied Sciences, Berlin, Germany

    Stephan Hinderlich

  2. Institute of Physiological Chemistry, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany

    Wenke Weidemann & Rüdiger Horstkorte

  3. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

    Tal Yardeni & Marjan Huizing

  4. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Tal Yardeni

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Hinderlich, S., Weidemann, W., Yardeni, T., Horstkorte, R., Huizing, M. (2013). UDP-GlcNAc 2-Epimerase/ManNAc Kinase (GNE): A Master Regulator of Sialic Acid Synthesis. In: SialoGlyco Chemistry and Biology I. Topics in Current Chemistry, vol 366. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2013_464

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