Muscle replenishment

This complex consists of at least 25 separate polypeptides, seven of which are encoded by mtDNA. Its catalytic action is to transfer electrons from NADH to ubiquinone, thus replenishing NAD concentrations. Complex I deficiency has been described in myopathic syndromes, characterized by exercise intolerance and lactic acidemia. In at least some patients it has been demonstrated that the defect is tissue specific and a defect in nuclear DNA is assumed. Muscle biopsy findings in these patients are typical of those in many respiratory chain abnormalities. Instead of the even distribution of mitochondria seen in normal muscle fibers, mitochondria are seen in dense clusters, especially at the fiber periphery, giving rise to the ragged-red fiber (Figure 10). This appearance is a hallmark of many mitochondrial myopathies. 

Muscle in the resting state predominantly utilizes fatty acids. The immediate source of energy for muscle contraction is ATP, which is rapidly replenished at the expense... 

The major fuels of skeletal muscle are glucose and fatty acids. Because of the enormous bulk, skeletal muscle is the body s major consumer of fuel. After a meal, under the influence of insulin, skeletal muscle takes up glucose to replenish glycogen stores and amino acids that are used for protein synthesis. Both excess glucose and amino acids can also be oxidized for energy. 

The observation of possibly increased IMCL levels in highly trained athletes led to a second focus of research in the field of sports medicine. Besides carbohydrates, lipids are the major fuel of skeletal muscle during work and rest. A variety of questions have to be answered. It was examined, whether exercise of various intensities alters IMCL levels, whether those changes depend on the duration of exercise, and finally, how IMCL are replenished during post-exercise recovery. 

After sustained physical activity, the enzyme is active in the muscles that have been exercising, which results in uptake of the fatty acids from the triacylglycerol in blood by these muscles. The fatty acids are esterifled within the muscle and the triacylglycerol so formed replenishes that which was used in the physical activity. 

Ca normally circulates in the bloodstream, within a 2.25-2.50 mmol concentration range, bound to proteins (40 5%), complexed with ions (8-10%), and ionized as Ca " " (45-50%) (Weaver and Heaney, 2006a). Circulating Ca in excess of that required for maintenance of plasma levels is ideally transferred from the blood to be deposited in bone via the bone formation process. The Ca concentration outside of blood vessels in the ECF that bathes cells is tightly regulated close to 1.25 mmol (Weaver and Heaney, 2006a), almost to the point of invariance. It is this ECF Ca pool that cells are immediately reliant upon to sustain vital cellular functions that are imminently critical to the maintenance of life (e.g., cardiac muscle contraction). Circulating Ca is constantly utilized to replenish ECF pools, and when Ca derived from dietary intake is insufficient to replace the amoimt of Ca used for replenishment, Ca in bone is transferred to the blood via a bone resorption process. 

After a period of intense muscular activity, the individual continues breathing heavily for some time, using much of the extra 02 for oxidative phosphorylation in the liver. The ATP produced is used for gluconeogenesis from lactate that has been carried in the blood from the muscles. The glucose thus formed returns to the muscles to replenish their glycogen, completing the Cori cycle (Fig. 23-18 see also Box 15-1). 

When the cell is activated for a long period of time, the relatively small supply of ATP present in the muscle cell may be depleted. A reservoir of another phosphorylated compound, phosphocreatine, capable of transferring its phosphoryl compound to ADP, is available to replenish the ATP supply. The reaction is... 

Muravskaya, 1978 Diana and Mackay, 1979 Shatunovsky, 1980). However, in all starved fish it is the lipid that is mobilized first, except possibly in the eel. In fatty fish, much lipid is used from the flesh, while in lean fish it is used from the liver. In both types of fish, muscle protein is mobilized only when the lipid resources fall below a critical level. Black and Love (1986) showed that energy substrates are mobilized in a definite sequence, white muscle protein, for example, being metabolized at an earlier stage than red muscle protein, while, on refeeding, the latter is replenished before the former. 

Proteolysis also provides carbon skeletons for gluconeogenesis. During starvation, degraded proteins are not replenished and serve as carbon sources for glucose synthesis. Initial sources of protein are those that turn over rapidly, such as proteins of the intestinal epithelium and the secretions of the pancreas. Proteolysis of muscle protein provides some of three-carbon precursors of glucose. However, survival for most animals depends on being able to move rapidly, which requires a large muscle mass, and so muscle loss must be minimized. 

The creatine synthesized in the liver is transported through the bloodstream to skeletal and heart muscle. It enters the mitochondria, where it is phosphorylated to crealine-P Creatine kinase catalyzes this reversible addition of a phosphate group, as shown in Figure 4.34. Creatine-P is unique in that its only known function is as an energy buffer. The creatine P formed in the mitochondria travels to the contractile proteins in the cytoplasm of the muscle fiber. The polymer, or complex, of contractile proteins is called a myofibril. Contraction of a myofibril is coupled to the hydrolysis of ATP to ADP. The immediate replenishment of ATP is catalyzed by a second creatine kinase, residing on the myofibril, that catalyzes the conversion of creatine-P to creatine. This reversal of the reaction takes place in the... 

The time course of use and replenishment of creatine is shown in the study of exercising human subjects reported in Figure 4.36, The subjects exercised on a stationary bicycle that was adjusted so that exhaustion would be reached after 6 minules. Muscle biopsies, taken before and after exercise, from the quadriceps femoris muscle of the leg were used for analysis of cneatine-P The data demonstrate that the reservoir of creatine-P, substantially depleted by the end of the exercise period, was rapidly repleted during the subsequent resting period. 

ContiioUcd studies of recovery from exercise demonstrated that the maxi mat rate of muscle glycogen replenishment is close to 7.0 mmul of glucose units as glycogen) per hour. How dues this rate compare with that of the subjects fed the uncontrolled diets described in Figure 4-3 (See Blom ei al, 1987.)... 

Pyruvate may be converted to oxaloacetate by pyruvate carboxylase, an enzyme found in tissues such as the liver and brain but not in muscle. -This reaction serves to replenish intermediates of the TCA cycle. 

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