Effects of hyperammonemia on brain protein kinase C substrates.

Abstract

Ammonia is a product of the degradation of proteins and of other compounds ; however, when it is in excess, ammonia is a toxic compound . A fiveto ten-fold increase in blood ammonia levels leads to alterations in the function of the central nervous system, and can lead to coma and death . To prevent these toxic effects, ureotelic animals have developed the urea cycle, which is mainly located in liver, and eliminates ammonia by incorporating it into urea, which is eliminated in urine . This maintains safe levels of ammonia in blood and tissues. However, when this process fails due to a congenital defect in the urea cycle enzymes or by impairment of liver function, the levels of ammonia in blood rise and can lead to altered brain function. This syndrome, known as hepatic encephalopathy, can lead to coma and death. Ammonia interferes with neurotransmission and with electrophysiological processes (Fan et al., 1990; Szerb and Butterworth, 1992 ; Raabe and Lin, 1984 ; Raabe, 1992 and 1994, Butterworth, 1994) . There are a number of human illnesses that are associated with increased levels of ammonia in blood, including liver cirrhosis, fulminant hepatic failure and congenital defects of urea cycle enzymes . Independently of its origin, in these situations the levels of ammonia in blood increase 5 to 10-fold, leading to hepatic encephalopathy, and high mortality . In fact, hepatic encephalopathy is one of the main causes of death in occidental countries . In Spain 12,000 people die every year for this reason, which represents about