High protein diet induces pericentral glutamate dehydrogenase and ornithine aminotransferase to provide sufficient glutamate for pericentral detoxification of ammonia in rat liver lobules |
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Authors: | Louis Boon Willie J C Geerts A Jonker Wouter H Lamers Cornelis J F Van Noorden |
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Institution: | (1) Tanox Pharma BV, Paasheuvelweg 15, 1105 BE Amsterdam, The Netherlands, NL;(2) Department of Anatomy and Embryology, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands, NL;(3) Department of Cell Biology and Histology, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands, NL;(4) Department of Cell Biology and Histology, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands e-mail: c.j.vannoorden@amc.uva.nl Tel.: +31-20-566-4970/4966, Fax: +31-20-697-4156, NL |
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Abstract: | The liver plays a central role in nitrogen metabolism. Nitrogen enters the liver as free ammonia and as amino acids of which
glutamine and alanine are the most important precursors. Detoxification of ammonia to urea involves deamination and transamination.
By applying quantitative in situ hybridization, we found that mRNA levels of the enzymes involved are mainly expressed in
periportal zones of liver lobules. Free ammonia, that is not converted periportally, is efficiently detoxified in the small
rim of hepatocytes around the central veins by glutamine synthetase preventing it from entering the systemic circulation.
Detoxification of ammonia by glutamine synthetase may be limited due to a shortage of glutamate when the nitrogen load is
high. Adaptations in metabolism that prevent release of toxic ammonia from the liver were studied in rats that were fed diets
with different amounts of protein, thereby varying the nitrogen load of the liver. We observed that mRNA levels of periportal
deaminating and transaminating enzymes increased with the protein content in the diet. Similarly, mRNA levels of pericentral
glutamate dehydrogenase and ornithine aminotransferase, the main producers of glutamate in this zone, and pericentral glutamine
synthetase all increased with increasing protein levels in the diet. On the basis of these changes in mRNA levels, we conclude
that: (a) glutamate is produced pericentrally in sufficient amounts to allow ammonia detoxification by glutamine synthetase
and (b) in addition to the catalytic role of ornithine in the periportally localized ornithine cycle, pericentral ornithine
degradation provides glutamate for ammonia detoxification.
Accepted: 16 March 1999 |
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