Amino acid metabolism in patients with a hereditary myopathy and paroxysmal myoglobinuria.

Amino acid metabolism of skeletal muscle was examined in two patients with a hereditary myopathy associated with elevated blood levels of lactate and pyruvate and paroxysmal myoglobinuria. Arterial concentrations as well as arm and leg exchange, respectively, of amino acids, lactate, pyruvate and oxygen were studied at rest and during exercise (16 and 33 W) using a bicycle ergometer. The patients' arterial concentrations of amino acids, lactate and pyruvate in the resting state were similar to those of healthy controls. During exercise a marked increase in lactate and pyruvate concentrations was seen in the patients, exceeding the small rise in healthy controls. The arterial alanine concentration rose during exercise in both patients (+120%, +125%), while no change was observed in the controls working at the same work load. No other amino acid showed a consistent rise during exercise. Instead, the arterial levels of the branched chain amino acids (valine, leucine, isoleucine) fell during exercise in the patients but not in the controls. Net release of alanine from the legs in patient 1 rose 2.5- and five-fold during exercise, while no change was seen in the controls. Alanine output from the working arms in patient 2 exceeded that of controls by 50%. In addition, the release of lactate and pyruvate during exercise was much augmented in both patients in comparison to controls. It is concluded that the rate of alanine formation by skeletal muscle during exercise is much increased in patients with this type of myopathy, associated with elevated levels of lactate and pyruvate. These findings lend support to the theory that the carbon skeletons for alanine synthesis by skeletal muscle are derived from muscle glycolysis.