Intravenous Infusion of α-Oxoisocaproate: Influence on Amino Acid and Nitrogen Metabolism in Patients with Liver Cirrhosis

Abstract

1. The metabolic effect of α-oxoisocaproate (4-methyl-2-oxovalerate) infusion was examined in six patients with cirrhosis and in nine healthy control subjects. The arterial concentrations of amino acids, urea, ammonia, insulin and catecholamines were determined in the basal state and during intravenous infusion of α-oxoisocaproate (300 μmol/min) for 150 min. The exchanges of amino acids and substrates across the splanchnic region, the brain and the leg were examined in the healthy subjects by a catheter technique. 2. Basal α-oxoisocaproate levels were similar in patients and control subjects. During infusion the concentrations of α-oxoisocaproate rose to 90–130 μmol/l; they were 20–35% lower in the patients. Arterial leucine concentration increased in both groups to 250–300 μmol/l. Valine and isoleucine concentrations decreased (50–60%) as did to a lesser extent the concentrations of aromatic amino acids and methionine. 3. Regional exchange of amino acids was not significantly influenced by α-oxoisocaproate infusion. Arterial urea concentration decreased (12%, P < 0.05) and ammonia levels rose (15–25%, P < 0.05) in both groups. In the patients both adrenaline (100%, P < 0.001) and noradrenaline concentrations were elevated (350%, P < 0.001) in the basal state; insulin levels were similar to those in control subjects. 4. It is concluded that α-oxoisocaproate is rapidly transaminated to leucine in patients with cirrhosis and in healthy control subjects. α-Oxoisocaproate infusion resembles leucine infusion in its influence on aromatic amino acid concentrations, but in addition it elicits increased ammonia levels and decreased urea formation.