Chapter 45: Metabolism of Muscle at Rest and during Exercise

Muscle contraction operates universally through the actin-myosin sliding filament mechanism controlled by intracellular calcium dynamics, yet the metabolic demands and adaptive responses differ substantially among muscle types. Skeletal muscle comprises type I fibers, characterized by slow contraction speed, high oxidative capacity, abundant mitochondria and myoglobin, and resistance to fatigue, alongside type II fibers that generate rapid force through anaerobic glycolysis but accumulate lactate and fatigue quickly. Dystrophin deficiency, seen in Duchenne and Becker muscular dystrophies, disrupts sarcolemmal integrity and severely impairs muscle function, illustrating the critical relationship between structural proteins and metabolic performance. Energy metabolism in muscle integrates multiple pathways including glycolysis, fatty acid oxidation, creatine phosphate buffering, and amino acid catabolism. Creatine, synthesized from glycine and arginine in the kidney and liver, is phosphorylated by creatine kinase to form creatine phosphate, which provides immediate ATP regeneration during high-demand periods; its degradation to creatinine serves clinically as a marker of renal function. Malonyl-CoA and ACC-2 regulate fatty acid entry into mitochondria via carnitine palmitoyltransferase, with AMPK activation promoting fat oxidation during energy stress. Cardiac muscle relies predominantly on oxidative phosphorylation of fatty acids, glucose, and lactate, making it particularly susceptible to ischemic damage and requiring therapeutic interventions like partial fatty acid oxidation inhibitors such as trimetazidine. During exercise, ATP hydrolysis increases up to one hundredfold, initially supported by anaerobic glycolysis with delayed oxygen availability, then transitioning to aerobic oxidation for sustained performance. Muscle uniquely regulates glycogenolysis through AMP, calcium, and epinephrine signals rather than glucagon, enabling rapid fuel mobilization. Lactate produced during exercise either recycles through the Cori cycle or oxidizes in heart and oxidative tissues. Extended moderate activity shifts fuel preference toward free fatty acids while preserving blood glucose for the brain. Branched-chain amino acids contribute both ATP and glutamine for ammonia buffering during acidosis, while the purine nucleotide cycle generates fumarate and ammonia for metabolic homeostasis. Training adaptations enhance muscle performance through increased glycogen storage capacity, mitochondrial proliferation, improved fatty acid oxidation efficiency, and structural hypertrophy in response to resistance training.