Glutamine and cell signaling in liver

In the liver, glutamine plays an important role in ammonia detoxication and the regulation of pH homeostasis ("Intercellular glutamine cycle"). In add ition, this amino acid regulates liver metabolism and transport by mechanis ms that cannot be attributed to its metabolism. Examples include the stimul ation of protein and glycogen synthesis and bile acid secretion and the inh ibition of proteolysis in liver. The major trigger for such effects is an i ncreased hepatocyte hydration due to the cumulative uptake of glutamine int o the cells, which activates osmosignaling pathways involving mitogen-activ ated protein kinases (MAPK). Glutamine- and hypoosmolarity-induced cell swe lling activates extracellular signal-regulated kinases (ERK) and p38(MAPK). Activation of these MAPK results in an increased capacity of bile acid exc retion into bile due to a rapid translocation of canalicular transport ATPa ses from a subcanalicular storage compartment to the canalicular membrane. Similarly, glutamine augments biliary excretion of cysteinyl leukotrienes i n endotoxin-treated rat livers. Also, the antiproteolytic effect of glutami ne is largely due to glutamine-induced cell swelling, which activates osmos ignaling pathways. Here, the glutamine-induced p38(MAPK) activation mediate s the inhibition of autophagic proteolysis at the level of autophagosome fo rmation.