TRICARBOXYLIC-ACID CYCLE INTERMEDIATES DURING INCREMENTAL EXERCISE INHEALTHY-SUBJECTS AND IN PATIENTS WITH MCARDLES-DISEASE

1. The importance of the level of tricarboxylic acid cycle intermediat es (malate, citrate and fumarate) for energy transduction during exerc ise has been investigated in six healthy subjects and in two patients with muscle phosphorylase deficiency (McArdle's disease). 2. Healthy s ubjects cycled for 10 min at low (50 W), moderate [130 +/- 6 W (mean SEM)] and high (226 +/- 12 W) work rates, corresponding to 26, 50 and 80% of their maximal O-2 uptake, respectively, Patients with McArdle' s disease cycled for 11-13 min at submaximal (40 W) rates, and to fati gue at maximal work rates of 60-90 W. 3. In healthy subjects, phosphoc reatine was unchanged during low work rates, but decreased to 79 and 3 2% of the initial level during moderate and high work rates, In patien ts with McArdle's disease, phosphocreatine decreased to 82 and 34% of the initial level during submaximal and peak exercise, Muscle lactate increased in healthy subjects during exercise at moderate and high wor k rates, but remained low in patients with McArdle's disease. 4. In he althy subjects, tricarboxylic acid cycle intermediates were similar at rest and at low work rates (0.48 +/- 0.04 mmol/kg dry weight), but in creased to 1.6 +/- 0.2 mmol/kg dry weight and 4.0 +/- 0.3 mmol/kg dry weight at moderate and high work rates, The tricarboxylic acid cycle i ntermediate level in patients with McArdle's disease was similar to th at in healthy subjects at rest, but was markedly reduced during exerci se when compared at the same relative intensity, The peak level of tri carboxylic acid cycle intermediates in patients with McArdle's disease was 22% of that in healthy subjects, However, when compared at the sa me absolute workload, tricarboxylic acid cycle intermediates were simi lar in patients with McArdle's disease and in healthy subjects. 5. The decrease in glutamate and increase in alanine suggest that the alanin e aminotransaminase reaction was the major anaplerotic process in heal thy subjects, However, in patients with McArdle's disease (n = 1), mus cle alanine remained unchanged and the purine nucleotide cycle may ins tead be the route of a limited anaplerosis during maximal exercise, Th e muscle content of glutamate and glutamine (n = 1) was markedly reduc ed in patients with McArdle's disease. 6. It is concluded that the tri carboxylic acid cycle intermediate level is related to the work rate i n healthy subjects, and that the attenuated peak level in patients wit h McArdle's disease may be a limitation for aerobic energy transductio n.