Pipecolic acid is regarded as a gamma-aminobutyric acid receptor agonist. Stereochemical studies of pipecolic acid were performed in patients with chronic liver diseases. Plasma D- and L-pipecolic acid were significantly elevated in 15 liver cirrhotic patients with no history of hepatic encephalopathy (1.05+/-0.24 micromol/l, 1.58+/-0.13 micromol/l, p < 0.01) and in 27 patients with chronic hepatic encephalopathy (1.58+/-0.50 micromol/l, 2.38+/-0.58 micromol/l, p<0.001) compared to 15 normal subjects. In seven patients with chronic hepatic encephalopathy orally treated with kanamycin, plasma pipecolic acid significantly decreased (D-acid: before 1.62+/-0.23 micromol/l, after 0.61+/-0.15 micromol/l; p<0.01, L-acid: before 2.43-0.52 micromol/l, after 2.23+/-0.11 micromol/l; p< 0.05). These results suggest that plasma pipecolic acid, particularly D-acid, is produced from D-lysine by intestinal bacteria in liver cirrhotic patients and that pipecolic acid could be involved in the pathogenesis of hepatic encephalopathy.
