Fasting and postprandial phenylalanine and leucine kinetics in liver cirrhosis

Abstract

To investigate body protein turnover and the pathogenesis of increased concentration of plasma phenylalanine in liver cirrhosis, we have studied phenylalanine and leucine kinetics in cirrhotic (diabetic and nondiabetic) patients, and in normal subjects, both in the postabsorptive state and during a mixed meal, using combined intravenous and oral isotope infusions. Postabsorptive phenylalanine concentration and whole body rate of appearance (Ra) were approximately 40% greater (P < 0.05) in patients than in controls. Leucine concentrations were comparable, but intracellular leucine Ra was also increased (P < 0.05), suggesting increased whole body protein breakdown. Postprandial phenylalanine Ra was also greater (P < 0.05) in the patients. This difference was due to a diminished fractional splanchnic uptake of the dietary phenylalanine (approximately 40% lower in the cirrhotics vs. controls, P < or = 0.05). Postprandial leucine Ra was also increased in the patients, but splanchnic uptake of dietary leucine was normal. Thus both increased body protein breakdown and decreased splanchnic extraction of dietary phenylalanine can account for the increased phenylalanine concentrations in liver cirrhosis.

Isoleucine infusion during “simulated” upper gastrointestinal bleeding improves liver and muscle protein synthesis in cirrhotic patients

“…The results of this study demonstrate that isoleucine infusion during intragastric administration of an amino acid solution that resembles the amino acid pattern of hemoglobin stimulates liver and muscle protein synthesis. In the control group, this normal response to administration of an amino acid mixture 18,19 was impaired.…”

“…In the present study, disposal and production of phenylalanine is calculated because phenylalanine is only incorporated in protein and is not produced de novo. The phenylalanine method has been proven to be valid in cirrhotic patients, [17][18][19] whereas it has been shown that leucine metabolism is altered in patients with cirrhosis. 20 (A detailed description of the method and its calculations is provided as Supplementary material at the HEPATOLOGY website [http://interscience.wiley.com/jpages/0270-9139/ suppmat/index.html].…”

Impairment of albumin and whole body postprandial protein synthesis in compensated liver cirrhosis

“…Such a resistance, in turn, may be secondary to alterations of liver architecture, circulation, and function, which are characteristic of this disease (6), including a shunt of insulin from the portal vein to the posthepatic circulation. A decreased first-pass splanchnic (liver) extraction of some dietary amino acids, such as phenylalanine (34), and the altered plasma profiles [i.e., the increased AAA concentrations and/or the decreased BCAA/AAA ratio (25)] might also have limited albumin synthesis. Among other possible alterations that are observed in cirrhosis (although not measured in this study), toxic effects by cytokines (2,38), as well as a decreased insulin-like growth factor I (IGF-I) concentration (12), could also be considered.…”

l-[1-13C] phenylalanine breath test results reflect the activity of phenylalanine hydroxylase in carbon tetrachloride acute injured rat liver

“…plasma into the liver, E = 0.2 (Matthews et al, 1993), that is even lower in patients with liver diseases (Tessari et al, 1994). Its elimination by the liver is heavily dependent on hepatocyte metabolism, but little on the hemodynamics of the liver.…”