Metabolism of Urea in the Liver of Ruminants:
The structure and function of the liver attests to the importance of removing potentially toxic NH3 from
blood of ruminants as well as other mammals. The enzymes of the ornithine cycle and enzymes catalyzing
transamination reactions are structurally oriented in mitochondria and cytosol of periportal and perivenous
hepatic cells to form urea from NH3 absorbed from the gut and to use glutamine synthesis as another pathway
to remove essentially all NH3 from hepatic portal blood (Figure 3). Periportal cells remove NH3 from hepatic
portal blood and use their enzymatic machinery to synthesize urea. The specialty of the perivenous cells is
production of glutamine through glutamine synthetase, thereby providing another opportunity to remove NH3
from circulation before blood enters the hepatic veins and subsequently general circulation. This two-stage NH3
removal system integrates with other systems, including gluconeogenesis, regulation of acid-base balance, and
interorgan N shuttles to derive the best metabolic control of substrate and product balances, nutrient supplies,
and nutrient needs of the organism (Leng and Nolan, 1984).