foto

PhD T.B.M. Hakvoort

Position
Research Associate
Main activities
Education, Research
Specialisation
Biochemistry, molecular biology,in vivo metabolism with stable isotopes
Focus of research

Proteins turn over continuously. Protein breakdown generates toxic ammonia. Glutamine and urea synthesis are the main pathways for ammonia detoxification, but their mutual dependence is still not sorted out. A ~5% reduction in urea synthesis causes lethal hyperammonemia, but a 35% reduction in glutamine synthesis produces no phenotype, even though glutamine synthetase is, thus far, held responsible for preventing hyperammonemia. Using tissue-specific knockout mice and stable isotope-based fluxomics, we investigate the interorgan dependence and (patho )physiological determinants of glutamine and urea synthesis, and the requirement of glutamine synthesis for urea synthesis. Environmental conditions that are studied include high-protein diets (high-protein diets are satiating and facilitate weight reduction), fasting (a proxy for cachexia), and intestinal bacterial overgrowth and acidosis (the encephalopathy-provoking condition in cirrhotic patients).

Key publications
  • He Youji, Hakvoort Theodorus B. M., Vermeulen Jacqueline L. M., Labruyère Wilhelmina T., de Waart D. Rudi, van der Hel W. Saskia, Ruijter Jan M., Uylings Harry B. M., Lamers Wouter H. Glutamine Synthetase Deficiency in Murine Astrocytes Results in Neonatal Death Glia 2010;58 (6):741-754 [PubMed]
  • He Youji, Hakvoort Theodorus B. M., Köhler S. Eleonore, Vermeulen Jacqueline L. M., de Waart D. Rudi, de Theije Chiel, ten Have Gabrie A. M., van Eijk Hans M. H., Kunne Cindy, Labruyere Wilhelmina T., Houten Sander M., Sokolovic Milka, Ruijter Jan M., Deutz Nicolaas E. P., Lamers Wouter H. Glutamine Synthetase in Muscle Is Required for Glutamine Production during Fasting and Extrahepatic Ammonia Detoxification Journal of biological chemistry 2010;285 (13):9516-9524 [PubMed]
  • Sokolović Milka, Sokolović Aleksandar, van Roomen Cindy P. A. A., Gruber Anna, Ottenhoff Roelof, Scheij Saskia, Hakvoort Theodorus B. M., Lamers Wouter H., Groen Albert K. Unexpected effects of fasting on murine lipid homeostasis - Transcriptomic and lipid profiling Journal of hepatology 2010;52 (5):737-744 [PubMed]
  • Sokolović Milka, Sokolović Aleksandar, Wehkamp Diederik, Ver Loren van Themaat Emiel, de Waart Dirk R., Gilhuijs-Pederson Lisa A., Nikolsky Yuri, van Kampen Antoine H. C., Hakvoort Theodorus B. M., Lamers Wouter H. The transcriptomic signature of fasting murine liver BMC genomics 2008;9 (1):528 [PubMed]
  • Stanulović Vesna S., Kyrmizi Irene, Kruithof-de Julio Marianna, Hoogenkamp Maarten, Vermeulen Jacqueline L. M., Ruijter Jan M., Talianidis Iannis, Hakvoort Theodorus B. M., Lamers Wouter H. Hepatic HNF4alpha deficiency induces periportal expression of glutamine synthetase and other pericentral enzymes Hepatology (Baltimore, Md.) 2007;45 (2):433-444 [PubMed]
All Publications
Research programmes

PhD T.B.M. Hakvoort (Promoties)

Prof. PhD W.J. de Jonge (Gastro-Intestinal diseases)

Prof. MD PhD G.R. van den Brink (Intestinal mucosal homeostasis and it's deregulation in inflammatory bowel disease and during oncogenesis)