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.
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.
Renner
Agnes B
AB
Institut für Biochemie und Molekularbiologie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, D-14195, Berlin, Germany. a.renner@berlin.de
Rieger
Kathrin
K
Grunow
Detlef
D
Zimmermann-Kordmann
Martin
M
Gohlke
Martin
M
Reutter
Werner
W
D000818:Animals; D002241:Carbohydrates / Q000737:chemistry*; D005260:Female; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism*; D009711:Nucleotides / Q000737:chemistry; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry*; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014018:Tissue Distribution; D014530:Uridine Diphosphate / Q000737:chemistry*; D014544:Uridine Triphosphate / Q000737:chemistry*; D026681:Vitamin B 6 Deficiency / Q000473:pathology*
D002241:Carbohydrates; D008055:Lipids; D009711:Nucleotides; D011134:Polysaccharides; D014530:Uridine Diphosphate; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D014544:Uridine Triphosphate