Principles of Biochemistry Volume 3 - A. Lehninger 1985

Selected Aspects of Human Biochemistry
Digestion, nutrient transport, and metabolic interrelationships
Skeletal muscles use ATP to perform mechanical work as needed

Skeletal Muscles as a whole account for more than 50% of the oxygen consumed by The Human Body at rest, and up to 90% during intense muscular activity. METABOLISM in skeletal muscles is primarily directed toward The production of ATP as an immediate source of energy for contraction and relaxation. Furthermore, skeletal muscles are adapted to perform mechanical work not continuously, but as needed. Sometimes, for example during a 100-meter sprint, skeletal muscles perform a massive amount of work in a very short time.

Depending on their activity level, skeletal muscles use glucose, free Fatty acids, or Ketone Bodies as fuel. In resting muscles, the primary substrates for Energy Metabolism are free Fatty Acids and ketone bodies delivered by the Blood from the Liver. These substrates undergo oxidation and breakdown to acetyl-CoA, which then enters The Citric Acid Cycle and is oxidized to CO₂. The concomitant transfer of electrons to oxygen provides the energy for Oxidative Phosphorylation AND The conversion of ADP to ATP. During moderate exercise, In addition to fatty acids and ketone bodies, muscles also utilize blood glucose. In this process, glucose is phosphorylated and broken down via Glycolysis to Pyruvate, which is subsequently oxidized in The Citric Acid cycle via acetyl-CoA. Finally, during maximum exertion, the consumption of ATP for contraction is so high that The rate of substrate (fuel) and oxygen delivery by the blood becomes insufficient. Under these conditions, the Glycogen stored within the muscles themselves is mobilized, breaking down to lactate via anaerobic glycolysis; this yields two molecules of ATP per cleaved glucose residue (Section 15.7, f). Thus, anaerobic glycolysis provides an additional amount of ATP beyond the baseline amount generated by the aerobic oxidation of other energy substrates in the citric acid cycle. The utilization of blood glucose and Muscle glycogen as rapidly mobilizable fuel for muscular work increases dramatically with an elevated secretion of adrenaline, which stimulates the liver to form glucose from glycogen for release into the blood, and Muscle tissue to break down glycogen to lactate (Chapter 25). Because skeletal muscles lack glucose-6-phosphatase, muscle glycogen is reserved exclusively for energy production via The Glycolytic Pathway.

Class="center">

Fig. 24-12. Interrelationship between metabolism in skeletal muscles and the liver. During heavy Physical Exercise, the energy source for skeletal muscles is glycogen, which breaks down via glycolysis. During the recovery period, a portion of the lactate formed in the muscles is transported to The Liver and converted into glucose, which enters the blood and is delivered to the muscles, where it is used to replenish glycogen stores.

However, muscle glycogen stores are small, and therefore there is an upper limit to The amount of energy that can be produced through glycolysis under maximum load conditions (e.g., during a sprint). Moreover, the accumulation of lactic acid and the resulting drop in pH, along with the Temperature increase caused by very high muscular activity, reduce metabolic efficiency in the muscles. For instance, during the recovery period following maximal physical exertion, an athlete continues to breathe heavily for some time. The additional oxygen consumed in the process is used to oxidize pyruvate, lactate, and other substrates, as well as to regenerate ATP and phosphocreatine in the muscles. Concurrently, blood lactate is converted in the liver via Gluconeogenesis into blood-borne glucose, which reaches the muscles and is used to restore glycogen reserves (Section 20.1). Thus, the additional oxygen consumed (the "oxygen debt") restores the normal metabolic state of the Organism through a series of processes involving metabolic cooperation between the muscles and the liver (Fig. 24-12).

There is also another pathway that provides skeletal muscles with a maximum amount of ATP under critical circumstances. Muscles contain a significant amount of phosphocreatine (Section 14.15), which, with the help of creatine kinase, can rapidly replenish the terminal phosphate groups of ATP released During Muscle contraction:

During periods of high contractile activity and intense glycolysis, the reaction is strongly shifted to the right, whereas during the recovery period, phosphocreatine is resynthesized from creatine at the expense of ATP.

ATP in skeletal muscles is required not only to drive the sliding of Actin filaments along Myosin filaments, or thick filaments (Section 14.14), but also for relaxation. Muscle contraction is initiated by an impulse arriving from a motor nerve; this impulse is transmitted to the transverse tubules and the sarcoplasmic reticulum, from which Ca²⁺ ions are released into the sarcoplasm. Subsequently, Ca²⁺ binds to troponin—a regulatory protein that transduces this signal

into the sliding of actin filaments powered by ATP energy. After the cessation of motor nerve impulses, Ca²⁺ ions must be removed from the sarcoplasm to allow muscle relaxation to occur. This is achieved by The transport of Ca²⁺ ions back into the sarcoplasmic reticulum via the Ca²⁺-transporting membrane ATPase. The transport of two Ca²⁺ ions into the sarcoplasmic reticulum requires the Hydrolysis of a single ATP molecule; in other words, Skeletal Muscle relaxation consumes nearly as much energy as its contraction.