Activation of branched-chain keto acid dehydrogenase by exercise

Abstract

The present study was conducted to investigate the metabolic regulation of leucine oxidation during exercise. Ten rats per group were run at 27 m/min (0% grade) on a treadmill for 30 and 120 min or until exhausted, and the total and basal activity of branched-chain keto acid dehydrogenase was examined in the muscle, liver, and heart. The total activity of the dehydrogenase in the heart, liver, or skeletal muscle was unchanged by exercise. However, exercise increased the basal activity levels of the dehydrogenase about 10-fold in muscle and 5-fold in heart. The basal dehydrogenase activity in the liver was unchanged by exercise. Activation of the dehydrogenase in both muscle and heart was statistically elevated after 30 min exercise and continued to increase during the remainder of the exercise bout. The basal activity of the dehydrogenase returned to resting levels by 10 min postexercise. The activation of the dehydrogenase in muscle and heart during exercise likely is due to dephosphorylation because activity of the enzyme in mitochondria isolated from exercised muscles reverts to control values when the mitochondria are incubated in the presence of ATP. Thus the increased leucine oxidation observed during exercise is due to activation of the branched-chain keto acid dehydrogenase by dephosphorylation. This is the first example of a large increase in branched-chain keto acid dehydrogenase activity caused by a physiological process. This demonstrates that the muscle's latent capacity of oxidize branched-chain amino acids is much larger than previously thought and that this capacity is used in exercising muscle.

Administration of endotoxin, tumor necrosis factor, or interleukin 1 to rats activates skeletal muscle branched-chain alpha-keto acid dehydrogenase.

“…KIC is a potent inhibitor of BCKAD-kinase, and in many conditions, muscle BCKAD activation correlates with plasma and intracellular concentrations of leucine (I19-21). However muscle BCKAD activation has been observed without concomitant increases in leucine, i.e., after the co-injection of a-methylprednisolone and insulin (20) in chronic acidosis (52), or after exercise (63). The intramitochondrial concentration of KIC, which affects BCKAD activation, reflects the intracellular leucine and KIC concentrations as well as the activity of the mitochondrial transport system for branched chain a-keto acids, which in turn is modulated by ApH (43).…”

“…Increased lactate production (50,55) may lower the cytosolic pH in muscle resulting in increased ApH, accumulation of intramitochondrial KIC, and BCKAD activation. Reduction in the intramitochondrial ATP/ADP ratio could also contribute to BCKAD activation (63). Further studies of the actual mechanism(s) by which cytokines and endotoxin activate BCKAD complex seem warranted; they may be relevant to proposed nutritional therapy of septic patients (64) and to the ongoing investigations of the use of cytokines in cancer therapy (65,66).…”

Modification by Exercise Training of Activity and Enzyme Expression of Hepatic Branched-Chain .ALPHA.-Ketoacid Dehydrogenase Complex in Streptozotocin-Induced Diabetic Rats.

“…Skeletal muscles have a markedly higher activity of the aminotransferase and a lower ac tivity of BCKDH complex, and rat liver has the reverse situation with respect to enzyme activities (3,(5)(6)(7). From these findings, the concept of an interorgan rela tionship in BCAA and BCKA metabolism has been pro posed (8).…”

Protein and Amino Acid Needs of the Strength Athlete

“…It is likely that the exercise-induced increased leucine oxidation is related to the activation of branched-chain keto acid dehydrogenase (linuting enzyme in the leucine oxidation pathway) by exercise intensity and/or duration (58,59,89). Further, the observed increases during endurance exercise are greater in humans than in rodents (52), perhaps due to greater muscle dehydrogenase activity (61).…”