Effects of intrabrachial arterial infusion of pyruvate on forearm tissue metabolism

Abstract

Postabsorptive release of alanine from forearm skeletal muscle is large relative to other amino acids, suggesting new synthesis by transamination of pyruvate. This hypothesis was tested and the pathway quantified in six subjects, each given two 30 min intrabrachial arterial pyruvate infusions. The first (12 mumoles/min) supplied approximately that amount of pyruvate produced endogenously by glycolysis in resting muscle. The second (36 mumoles/min) approximated endogenous pyruvate production by glycolysis during moderate exercise. Changes in balance across forearm tissues of pyruvate, glucose, lactate, and amino acids were measured. The time-course of pyruvate equilibration across fore-arm muscles was detailed in three additional subjects. The two infusions increased arterial pyruvate from 64 to 674 and 1776 mumoles/liter respectively. Muscle consumed 72% of the exogenous pyruvate during both infusions. Outputs of lactate and alanine increased, accounting respectively for 30.3 and 6.7% of the pyruvate at the low infusion rate, and 17.1 and 3.8% at the high rate. The remaining pyruvate probably was oxidized. Muscle release of valine, isoleucine, and leucine decreased during the high dose infusion. Additionally, adipose tissue plus skin released more alanine and lactate during the high dose infusion. Other metabolies were unchanged.Thus, both muscle and adipose tissue plus skin synthesize alanine from pyruvate. Lactate production considerably exceeds that of alanine. In muscle, increased availability of intracellular pyruvate serving as a nitrogen acceptor may facilitate branched chain amino acid oxidation. Muscle consumption of infused pyruvate is rapid, and detailed studies of its equilibration suggest that passage across the muscle cell membrane is rate limiting.