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Liver-specific increase of UTP and UDP-sugar concentrations in rats induced by dietary vitamin B6-deficiency and its relation to complex N-glycan structures of liver membrane-proteins

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Abstract

This is the first known report on the influence of vitamin B6-deficiency on the concentration of UDP-sugars and other uracil nucleotides in rats. Animals aged 3 weeks or 2 months were fed a vitamin B6-free diet for periods varying from 3 days to 7 weeks. Nucleotides were quantified by enzymatic-photometry and by SAX-high precision liquid chromatography. In 3 week-old rats, vitamin B6-deficiency resulted in an up to 6.3-fold increase in the concentrations of UTP, UDP, UMP and UDP-sugars and less of CTP in rat liver, while no changes were observed in older rats. In young rats, the concentration of uracil nucleotides started to increase after 1 week diet, with a maximum after 2 weeks. After 5 weeks, the concentrations returned to normal values. In heart, lungs, kidney and brain, concentrations were measured after 2 weeks diet in young rats. In contrast to liver, the heart muscle uracil nucleotide concentrations were decreased by 40%. In kidney, the sum of UTP, UDP and UMP showed a decrease of 40%, whereas UDP-sugars were increased 1.4-fold. In the lungs, nucleotide concentrations were mostly unaffected by vitamin B6-deficiency, despite a 70% increase of UDP-GA. In brain, UDP-Glc, UDP-Gal and the sum of CTP and CDP showed an increase of 30–50%. We became surprised that the increased UDP-sugar concentrations did not influence the structure of liver plasma membrane-N-glycans. Despite the 4 to 6-fold increase of UTP and UDP-sugars, no changes in the complexity or sialylation of these N-glycans could be detected. This study demonstrates that, especially in liver, pyridoxal phosphate is closely involved in the control of uracil nucleotides during a defined period of development. In contrast to in vitro experiments, in vivo N-glycan biosynthesis in liver is regulated by a more complex or higher mechanism than substrate concentrations.

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Acknowledgements

This work is dedicated to Dr. Martin Zimmermann-Kordmann, who suddenly died. We are deeply saddened by the loss of an excellent scientist and warm-hearted friend and colleague.

We are grateful to F. Hoffmann-La Roche Ltd, Switzerland, for providing us with vitamin B6-deficient feed and thank Dr. T. Scott, Leeds, for critically reading the manuscript. This work was supported by the Sonnenfeld-Stiftung.

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Authors and Affiliations

  1. Institut für Biochemie und Molekularbiologie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, D-14195, Berlin, Germany

    Agnes B. Renner, Kathrin Rieger, Detlef Grunow, Martin Zimmermann-Kordmann, Martin Gohlke & Werner Reutter

  2. Augenklinik, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200, Berlin, Germany

    Agnes B. Renner

  3. Medizinische Klinik III, Hämatologie, Onkologie und Transfusionsmedizin,Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200, Berlin, Germany

    Kathrin Rieger

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  1. Agnes B. Renner
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  2. Kathrin Rieger
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  4. Martin Zimmermann-Kordmann
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Correspondence to Agnes B. Renner.

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Agnes B. Renner and Kathrin Rieger contributed equally.

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Renner, A.B., Rieger, K., Grunow, D. et al. Liver-specific increase of UTP and UDP-sugar concentrations in rats induced by dietary vitamin B6-deficiency and its relation to complex N-glycan structures of liver membrane-proteins. Glycoconj J 24, 531–541 (2007). https://doi.org/10.1007/s10719-007-9048-x

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