Effects of Ingested Steak and Infused Leucine on Forelimb Metabolism in Man and the Fate of the Carbon Skeletons and Amino Groups of Branched-Chain Amino Acids

Abstract

1. The effects of ingested grilled beef steak (250 g raw weight of lean meat) and infusion of leucine (3.8 g) on human forelimb metabolism were studied by monitoring the concentrations of various metabolites in arterial (A) and venous (V) blood of four overnight fasted and rested men. 2. The mean basal A—V for branched-chain 2-oxo acid (BCOA) was small (−3.6 μmol/l). After ingestion of steak or administration of leucine there were large positive increases in the A—V for branched-chain amino acid (BCAA) but increase in the negative A—V for BCOA was relatively small. 3. Within 2 h of ingestion of steak, BCAA accounted for approx. 50% of those amino acids with a positive A—V and glutamine for up to 75% of those with a negative A—V; the negative A—V for alanine decreased to 10% of its basal value. Infusion of leucine produced a large positive A—V for leucine by forelimb, a doubling in the negative A—V for glutamine and a rise in the blood glutamine concentration; the negative A—V for alanine was virtually unchanged and the blood alanine concentration showed a late significant decrease. 4. After ingestion of steak there was a two- to three-fold rise in the arterial insulin concentration, little change in the positive A—V for glucose and a decreased negative A—V for ‘glycolytic products’ (alanine + lactate + pyruvate), suggesting increased utilization of glucose carbon. Infusion of leucine doubled the arterial insulin concentration; the A—V for glucose decreased, that for lactate, pyruvate and alanine remained unchanged, suggesting decreased utilization of glucose carbon. 5. Circulating BCOA was distributed almost entirely in the plasma space. 6. in a variety of clinical conditions (insulin-dependent diabetes, cirrhosis, muscular dystrophy and starvation), the basal plasma concentrations of BCOA correlated well with those of BCAA (r = 0.989). Infusion of leucine increased the plasma BCAA/BCOA ratio to the same extent (about 40%) in each clinical condition despite considerable variations in the rate of leucine clearance. 7. The observations indicate that both ingested steak and infused leucine produce important changes in the selection of respiratory fuels by the human forelimb, that BCOA is preferentially oxidized rather than released from human limb tissues, and that glutamine, not alanine, is the major amino group carrier leaving the forelimb both after a protein meal and after leucine administration. Changes in cellular uptake or transamination of leucine appear not to be responsible for the varied rates of leucine clearance in a variety of clinical conditions.