Metabolic Effects of Carnitine and Carnitine Analogs
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Cirrhosis of the liver is a common and serious disease with a poor prognosis (1). Loss of liver perfusion and function compromises hepatic detoxification reactions and exposes the central nervous system (CNS) to amino acid imbalances and to multiple toxins including ammonia, mercaptans, short-chain fatty acids, and “middle” molecular weight molecules (2). Although all of these molecules contribute individually and perhaps synergistically to hepatic encephalopathy, there is abundant evidence that elevated CNS ammonia levels are a major factor. Ammonia concentrations are often high in the blood and cerebrospinal fluid of patients with liver disease, and ammonia infusion into patients with significant portacaval shunting evokes a reaction clinically indistinguishable from impending hepatic coma. In experimental animals, acute administration of ammonium salts causes convulsions, coma and death. Although several therapies directed at hepatic encephalopathy-associated ammonia intoxication have been devised, none is completely effective in reversing the morbidity and mortality of the disorder. Better methods for controlling ammonia metabolism and toxicity are clearly needed.
KeywordsAmmonium Acetate Hepatic Encephalopathy Maple Syrup Urine Disease Ammonia Toxicity Urea Synthesis
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