As of the February 15, 2018 data cutoff date, patient 1 has been followed for 24 weeks, patient 2 for 20 weeks, and patient three for 12 weeks The first patient's rate of ureagenesis
was normalized, maintained and then substantially increased over 24 weeks.
Interestingly, both studies found that protein doses greater than 20 grams resulted in an overabundance of available amino acids that subsequently resulted in an increased rate of amino acid oxidation and ureagenesis
The liver indeed normally exhibits metabolic zonation, that is, heterogenous distribution of metabolic functions across the lobule; in particular, oxygen-dependent functions like gluconeogenesis, ureagenesis
, and oxidative phosphorylation predominate in the periportal region, whereas glycolysis, lipogenesis, and xenobiotic metabolism take place predominantly in the pericentral (perivenous) region [22,23].
Relationships between ureagenesis
and gluconeogenesis in ruminants fed a high content of nitrogen.
Inhibition of ureagenesis
by valproate in rat hepatocytes.
Influence of hepatic ammonia removal on ureagenesis
, amino acid utilization and energy metabolism in the ovine liver.
The PICM-19 cells grown in vitro synthesize liver specific proteins such as albumin and transferrin, and display enhanced liver-specific functions such as ureagenesis
and cytochrome P450 activity.
Correction of ureagenesis
after gene transfer in an animal model and after liver transplantation in humans with ornithine transcarbamylase deficiency.
Disruption of this process promotes the esterification of fatty acids in the cytoplasm to triglyceride, robs the cell of energy, and leads to hyperammonemia via inhibition of ureagenesis