Chronic hyperammonemia alters protein phosphorylation and glutamate receptor-associated signal transduction in brain.
There is substantial evidence that hyperammonemia is one of the main factors contributing to the neurological alterations found in hepatic encephalopathy. The mechanisms by which chronic moderate hyperammonemia affects brain function involves alterations in neurotransmission at different steps. This article reviews the effects of hyperammonemia on phosphorylation of key brain proteins involved in neurotransmission (the microtubule-associated protein (MAP-2), Na+/K+-ATPase and NMDA receptors). The physiological function of these proteins is modulated by phosphorylation and its altered phosphorylation in hyperammonemia may contribute to impairment of neurotransmission. The effects of chronic hyperammonemia on signal transduction pathways associated to glutamate receptors, such as the glutamate-nitric oxide (NO)-cGMP pathway, are also reviewed. The possible contribution of the impairment of this pathway in brain in vivo to the neurological alterations present in patients with hepatic encephalopathy is discussed.
Corbalán
Regina
R
Laboratory of Neurobiology, Instituto de Investigaciones Citológicas, FVIB, Amadeo de Saboya, 4, 46010, Valencia, Spain.
Hernández-Viadel
Mariluz
M
Llansola
Marta
M
Montoliu
Carmina
C
Felipo
Vicente
V
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002908:Chronic Disease; D006801:Humans; D022124:Hyperammonemia / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017470:Receptors, Glutamate / Q000378:metabolism*; D015398:Signal Transduction
D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate