Branched-chain amino acids and ammonia metabolism in liver disease: therapeutic implications
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
23756281
DOI
10.1016/j.nut.2013.01.022
PII: S0899-9007(13)00090-7
Knihovny.cz E-resources
- Keywords
- Alpha-ketoglutarate, Glutamine, Liver cirrhosis, Nutrition, Phenylbutyrate,
- MeSH
- Ammonia metabolism MeSH
- Phenylbutyrates metabolism MeSH
- Glutamine metabolism MeSH
- Liver Cirrhosis drug therapy MeSH
- Hepatic Encephalopathy drug therapy MeSH
- Muscle, Skeletal drug effects metabolism MeSH
- Ketoglutaric Acids metabolism MeSH
- Kidney drug effects metabolism MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Amino Acids, Branched-Chain pharmacology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Ammonia MeSH
- Phenylbutyrates MeSH
- Glutamine MeSH
- Ketoglutaric Acids MeSH
- Amino Acids, Branched-Chain MeSH
The rationale for recommendation of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in treatment of liver failure is based on their unique pharmacologic properties, stimulatory effect on ammonia detoxification to glutamine (GLN), and decreased concentrations in liver cirrhosis. Multiple lines of evidence have shown that the main cause of the BCAA deficiency in liver cirrhosis is their consumption in skeletal muscle for synthesis of glutamate, which acts as a substrate for ammonia detoxification to GLN and that the BCAA administration to patients with liver failure may exert a number of positive effects that may be more pronounced in patients with marked depression of BCAA levels. On the other hand, due to the stimulatory effect of BCAA on GLN synthesis, BCAA supplementation may lead to enhanced ammonia production from GLN breakdown in the intestine and the kidneys and thus exert harmful effects on the development of hepatic encephalopathy. Therefore, to enhance therapeutic effectiveness of the BCAA in patients with liver injury, their detrimental effect on ammonia production, which is negligible in healthy people and/or patients with other disorders, should be avoided. In treatment of hepatic encephalopathy, simultaneous administration of the BCAA (to correct amino acid imbalance and promote ammonia detoxification to GLN) with α-ketoglutarate (to inhibit GLN breakdown to ammonia in enterocytes) and/or phenylbutyrate (to enhance GLN excretion by the kidneys) is suggested. Attention should be given to the type of liver injury, gastrointestinal bleeding, signs of inflammation, and the dose of BCAA.
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