title: Ammonia and amino acid profiles in liver cirrhosis: effects of variables leading to hepatic encephalopathy.
abstract: Hyperammonemia and severe amino acid imbalances play central role in hepatic encephalopathy (HE). In the article is demonstrated that the main source of ammonia in cirrhotic subjects is activated breakdown of glutamine (GLN) in enterocytes and the kidneys and the main source of GLN is ammonia detoxification to GLN in the brain and skeletal muscle. Branched-chain amino acids (BCAA; valine, leucine, and isoleucine) decrease due to activated GLN synthesis in muscle. Aromatic amino acids (AAA; phenylalanine, tyrosine, and tryptophan) and methionine increase due to portosystemic shunts and reduced ability of diseased liver. The effects on aminoacidemia of the following variables that may affect the course of liver disease are discussed: nutritional status, starvation, protein intake, inflammation, acute hepatocellular damage, bleeding from varices, portosystemic shunts, hepatic cancer, and renal failure. It is concluded that (1) neither ammonia nor amino acid concentrations correlate closely with the severity of liver disease; (2) BCAA/AAA ratio could be used as a good index of liver impairment and for early detection of derangements in amino acid metabolism; (3) variables potentially leading to overt encephalopathy exert substantial but uneven effects; and (4) careful monitoring of ammonia and aminoacidemia may discover important break points in the course of liver disease and indicate appropriate therapeutic approach. Of special importance might be isoleucine deficiency in bleeding from varices, arginine deficiency in sepsis, and a marked rise of GLN and ammonia levels that may appear in all events leading to HE.
authors.affiliation: Department of Physiology, Charles University Prague, Medical Faculty in Hradec Kralove, Czech Republic. Electronic address: Holecek@lfhk.cuni.cz.
authors.forename: Milan
authors.initials: M
authors.lastname: Holecek
mesh_terms: D024322:Amino Acids, Aromatic / Q000097:blood*; D000597:Amino Acids, Branched-Chain / Q000097:blood*; D000641:Ammonia / Q000097:blood*; D001921:Brain / Q000378:metabolism; D004044:Dietary Proteins / Q000008:administration & dosage; D005973:Glutamine / Q000097:blood; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000473:pathology; D006801:Humans; D022124:Hyperammonemia / Q000097:blood / Q000473:pathology; D007249:Inflammation / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism
chemical_list: D024322:Amino Acids, Aromatic; D000597:Amino Acids, Branched-Chain; D004044:Dietary Proteins; D005973:Glutamine; D000641:Ammonia
keywords: Acute-on-chronic liver failure; Branched-chain amino acids; Glutamine; Nutrition