Aromatic amino acid metabolism during liver failure.
Liver failure is associated with hepatic encephalopathy (HE). An imbalance in plasma levels of aromatic amino acids (AAA) phenylalanine, tyrosine, and tryptophan and branched chain amino acids (BCAA) and their BCAA/AAA ratio has been suggested to play a causal role in HE by enhanced brain AAA uptake and subsequently disturbed neurotransmission. Until recently, data on this subject and the role of the liver and splanchnic bed were scarce, particularly in humans, due to inaccessibility of portal and hepatic veins. Here, we discuss, against a background of relevant literature, data obtained in patients undergoing liver resection or with a transjugular intrahepatic portasystemic stent shunt (TIPSS), where these veins are accessible. The BCAA/AAA ratio remained unchanged after major liver resection, but plasma AAA levels were inversely correlated (P < 0.001) with residual liver volume, in keeping with the observed hepatic AAA uptake. In patients with stable cirrhosis and a TIPSS, the plasma BCAA/AAA ratio was lower than in controls (1.19 +/- 0.09 vs. controls: 3.63 +/- 0.34). Gastrointestinal bleeding in cirrhotics with a TIPSS induced disturbances in BCAA levels and the BCAA/AAA ratio and induced catabolism, which could partly be corrected by isoleucine administration. AAA may be important in the pathogenesis of HE, but it is unlikely that they are the sole factors. HE most likely is a syndrome with multifactorial pathogenesis, where hyperammonemia, AAA/BCAA imbalances, inflammation, brain edema, and neurotransmitter changes interact. Novel therapies to normalize AAA levels in patients with liver failure (such as the molecular adsorbent recirculating system dialysis device) should probably be combined with supplementation of e.g. isoleucine and enhancing ammonia excretion by the kidneys.
Dejong
Cornelis H C
CH
Department of Surgery, Nutrition and Toxicology Institute Maastricht, Maastricht University, the Netherlands. chc.dejong@ah.unimaas.nl
van de Poll
Marcel C G
MC
Soeters
Peter B
PB
Jalan
Rajiv
R
Olde Damink
Steven W M
SW
D024322:Amino Acids, Aromatic / Q000378:metabolism*; D000641:Ammonia / Q000378:metabolism*; D001692:Biological Transport; D006801:Humans; D017093:Liver Failure / Q000097:blood / Q000378:metabolism*; D010649:Phenylalanine / Q000097:blood; D012016:Reference Values; D014364:Tryptophan / Q000097:blood; D014443:Tyrosine / Q000097:blood
D024322:Amino Acids, Aromatic; D014443:Tyrosine; D010649:Phenylalanine; D000641:Ammonia; D014364:Tryptophan