DEFECTIVE NONOXIDATIVE LEUCINE DEGRADATION AND ENDOGENOUS LEUCINE FLUX IN CIRRHOSIS DURING AN AMINO-ACID INFUSION

The metabolic fate of leucine's first and second carbon may be differe nt depending on the tissue in which leucine is metabolized, as well as the prevailing hormonal milieu of that tissue. However, previous stud ies of leucine kinetics in humans have used only leucine labeled (as t racer) at the first carbon position. Because cirrhosis is associated w ith factors (such as insulin resistance and altered fuel substrate uti lization) that may influence how leucine is degraded, the kinetics of leucine's first and second carbon using a simultaneous infusion of [1( -14)C] leucine and [2-C-13] leucine were studied in the postabsorptive state and during an amino acid infusion in 6 stable cirrhotic patient s and 6 matched controls. The data were normalized for different body compartments that were quantified from the dilution of Hz [(18)0] and bromide. The body cell mass, but not body weighs or fat-free body mass , was decreased in cirrhosis (P < .001). In response to the amino acid infusion, total leucine appearance from proteolysis and leucine's inc orporation into protein increased significantly in both groups, but we re higher in cirrhotic patients. Endogenous protein breakdown decrease d in normals but remained unchanged in cirrhosis. These alterations in leucine metabolism became more prominent when data were expressed bas ed on the body cell mass rather than on body weight. The oxidation of leucine's first carbon (C-1) was decreased in cirrhosis, but the oxida tion of leucine's second carbon (C-2) did not differ between groups du ring both the postabsorptive period and the amino acid infusion, while nonoxidative leucine degradation [the difference between the oxidatio n of leucine's (C-1) and (C-2)] was also decreased in cirrhosis. In ad dition, there was a positive correlation between nonoxidative leucine degradation (which represents leucine incorporation into fat), and the respiratory quotient obtained from indirect calorimetry (r = .87; P < .001). These data suggest that the extent of leucine carbon oxidation is dependent on whether fat or carbohydrate is the prevailing fuel su bstrate. In addition, cirrhotic patients have decreased nonoxidative l eucine degradation and are unable to suppress endogenous protein break down normally in response to amino acid administration. These abnormal ities may contribute to the diminished fat stores and body cell mass c ommonly observed in cirrhosis.