The effect of trauma on protein metabolism was investigated in the whole body, muscle, and liver in severely head-injured patients presenting an acute inflammatory response by comparison to fed control subjects receiving a similar diet. Nonoxidative leucine disposal (an index of whole body protein synthesis) and muscle, albumin, and fibrinogen synthesis were determined by means of a primed, continuous infusion ofl-[1-13C]leucine. Nonoxidative leucine disposal increased by 28% in the patients ( P < 0.02). Fractional muscle protein synthesis rate decreased by 50% ( P < 0.01) after injury. Fractional and absolute fribrinogen synthesis rates were multiplied by two and nine, respectively, after injury ( P< 0.001). Albumin levels were lower in patients (25.2 ± 1.2 g/l, means ± SE) than in controls (33.7 ± 1.2 g/l, P < 0.001). However, fractional albumin synthesis rates were increased by 60% in patients (11.4 ± 1.0%/day) compared with controls (7.3 ± 0.4%/day, P < 0.01). Therefore, 1) head trauma induces opposite and large changes of protein synthesis in muscle and acute-phase hepatic proteins, probably mediated by cytokines, glucocorticoids, and other stress hormones, and 2) in these patients, hypoalbuminemia is not due to a depressed albumin synthesis.

The influence of the protein content of the meal on protein turnover was investigated in the splanchnic bed and in the remaining parts of the body in humans. Two groups of five subjects consumed every 20 min a liquid formula providing either 1.5 g protein x kg(-1) x day(-1) (P) or no protein (PF). L-[1-(13)C]leucine and L-[5,5,5-(2)H3]leucine were administered by vein and gut, respectively. An open two-pool model was developed to calculate leucine kinetics in both compartments, with the assumption that the enrichment of the tracers incorporated into very low density lipoprotein apolipoprotein B100 at isotopic steady state could reflect the leucine labeling in the splanchnic region. Nonsplanchnic uptake and release of leucine were not significantly different in the two groups. Within the splanchnic area, leucine uptake was 2.1 times higher in the P than in the PF group (P < 0.01), whereas leucine release was reduced but not significantly (-19%) in the P group compared with the PF group. Moreover, data derived from this model showed that protein intake induced an increase in whole body protein synthesis and no change in whole body protein breakdown. Albumin synthesis, as well as its contribution to whole body protein synthesis, was significantly enhanced by protein intake.

To determine if the molecular form of nitrogen intake affects protein metabolism during feeding, 12 normal volunteers received, by continuous nasogastric infusion, a protein or a peptide-based diet. Leucine kinetics (oral [13C]leucine and intravenous [2H3]leucine) were measured during the following three consecutive periods: first carbohydrates and lipids alone, then with either whole casein or oligopeptides in a randomized crossover design, with these two latter periods being isonitrogenous, isocaloric, and of identical amino acid compositions. Leucine concentration, turnover, oxidation, and nonoxidative disposal increased during nitrogen administration (all P < 0.01) and were higher with oligopeptides than with casein (242 +/- 44 vs. 188 +/- 31 mumol/l; 2.75 +/- 0.45 vs. 2.23 +/- 0.31; 1.14 +/- 0.19 vs. 0.82 +/- 0.22 mumol.kg-1.min-1, all P < 0.001; 1.64 +/- 0.32 vs. 1.44 +/- 0.33 mumol.kg-1.min-1, P < 0.05, respectively). Endogenous leucine production was less inhibited by oligopeptides than by casein (0.82 +/- 0.41 vs. 0.38 +/- 0.31 mumol.kg-1.min-1, P < 0.001), whereas splanchnic extractions were similar. Finally, leucine balance was more positive with casein than with oligopeptides (P < 0.001). In conclusion, the response of leucine kinetics to feeding is modified by the molecular form of nitrogen intake, with the oligopeptides inducing a higher oxidation and protein synthesis and a lesser inhibition of protein breakdown.

The estimation of the hepatic protein synthesis precursor pool was investigated through the measurement of very low-density lipoprotein (VLDL) apolipoprotein (apo)B100 labeling in healthy volunteers. L-[1-13C]leucine and L-[5,5,5-2H3]leucine were administered intravenously and intragastrically, respectively. Subjects were continuously fed with isoenergetic meals providing either 16% protein or no protein. The labeling of leucine incorporated into VLDL apoB100 (leucine-apoB) was lower than plasma leucine or alpha-ketoisocaproate (KIC) enrichments with the intravenous tracer. By contrast, with the oral tracer, leucine-apoB enrichment was higher than either plasma free leucine or KIC labeling. The KIC and leucine-apoB enrichments relative to plasma leucine enrichment were not affected by protein intake. Albumin or fibrinogen synthesis rates were similar whatever the administration route of the tracer when leucine-apoB was used to indicate the precursor, which was not the case for plasma leucine or KIC. The present data suggest that leucine-apoB enrichment represents a reliable indicator of the hepatic precursor pool for protein synthesis. The effect of dietary protein on the calculated rates of albumin and fibrinogen synthesis is also reported in relation to the choice of the precursor.