Biological Chemistry - Berezov, T. T., Korovkin, B. F. 1998

Muscle Tissue
Biochemical Changes in Muscles in Pathology

Common features of most Muscle diseases (progressive muscular dystrophies, muscle atrophy resulting from denervation, tenotomy, polymyositis, certainavitamins deficiencies, etc.) include a sharp decrease in the content of myofibrillar Proteins in Muscles, an increased concentration of stromal proteins, and elevated levels of certain sarcoplasmic proteins, including myoalbumin. Along with Changes in the fractional composition of Muscle Proteins, muscle lesions are accompanied by a decline in ATP and creatine phosphate levels. For example, 12 days after denervation, the ATP content in the denervated gastrocnemius muscle of a rabbit drops by more than half. Other notable findings include a reduction in the ATPase activity of contractile proteins (Myosin) and a decrease in The amount of imidazole-containing dipeptides.

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Fig. 20.9. Schematic representation of THE ORIGIN OF creatinuria in progressive muscular dystrophy (after D.L. Ferdman).

In progressive muscular dystrophies and other disorders associated with The breakdown of Muscle tissue, shifts in the phospholipid composition of muscles are frequently observed: the levels of phosphatidylcholine and phosphatidylethanolamine drop significantly, while the concentrations of sphingomyelin and lysophosphatidylcholine increase. To this day, the exact mechanisms underlying changes in the phospholipid composition of muscle tissue during pathology remain unclear, and The Role of these shifts in the Pathogenesis of muscular dystrophies is still unknown.

Many forms of muscle tissue pathology are characterized by impaired creatine METABOLISM and its enhanced urinary excretion (creatinuria). Despite numerous studies and an Abundance of empirical data, the question regarding the causes of creatinuria in muscle diseases cannot be considered conclusively resolved.

It is generally accepted that creatinuria in patients with myopathy results from impaired mechanisms of creatine retention and phosphorylation in Skeletal Muscle. If the synthesis of creatine phosphate is disrupted, creatinine is not formed either, leading to a sharp drop in its urinary concentration. As a result of creatinuria and impaired creatine synthesis, the urinary creatine ratio (creatine/creatinine) increases dramatically. This mechanism is illustrated in Fig. 20.9.

In muscle tissue pathology, a distinct pattern in enzyme activity changes can be observed: The activity of Enzymes localized in the sarcoplasm decreases; the activity of Cell/35.html">Mitochondria-associated enzymes changes only slightly; and the activity of lysosomal enzymes increases markedly. Finally, it has been demonstrated that many muscular disorders involve shifts in the cAMP system, specifically: a decrease in cAMP content within muscle tissue, an increase in phosphodiesterase activity, and an impaired ability of adenylate cyclase to be activated by adrenaline and sodium fluoride.

Impaired myocardial metabolism in CORONARY Heart DISEASE. Ischemic myocardium is characterized by reduced Oxidative Phosphorylation AND enhanced Anaerobic Metabolism. An early upregulation of Glycogenolysis and Glycolysis—fueled by Glycogen present in The Heart muscle and glucose rapidly taken up by the myocardium in the initial stage of ischemia—occurs as a result of elevated intracellular concentrations of catecholamines and cAMP. This, in turn, stimulates The formation of the active phosphorylase form (phosphorylase a) and activates Phosphofructokinase, a key glycolytic enzyme. However, even maximally enhanced anaerobic metabolism cannot protect the already damaged hypoxic myocardium for long. Very soon, glycogen reserves are depleted, and glycolysis slows down due to intracellular acidosis, which inhibits phosphofructokinase.

Cellular levels of ATP and creatine phosphate drop sharply as a consequence of impaired mitochondrial oxidative phosphorylation. One of the earliest manifestations of this state is compromised membrane permeability. The loss of membrane integrity promotes the efflux of ions from The Cell, including K⁺ ions and enzymes. Energy depletion, ionic imbalances, and significant alterations in various membrane reservoirs that regulate intracellular calcium levels lead to the inhibition of muscle cell functional activity and their eventual death. During this same period, changes in myocardial protein composition become evident (a sharp decline in myofibrillar proteins and the accumulation of stromal proteins). The impairment of carbohydrate, protein, and Lipid Metabolism (free Fatty acids are not oxidized, but are preferentially incorporated into triglycerides) during myocardial infarction is reflected in fatty infiltration of the heart muscle.

The extent of myocardial damage during ischemia, the decrease in enzyme activity within the heart muscle, and the elevation of corresponding enzyme activities in Blood serum (such as creatine kinase) correlate significantly with one another. It must be recognized that determining the serum activities of creatine kinase, AST, and LDH is the most sensitive diagnostic test for myocardial infarction. The elevation of these enzymes, particularly creatine kinase, is consistent and most pronounced. It is also valuable to analyze serum creatine kinase isoenzyme spectra (an increase in the MB isoenzyme activity) and LDH spectra (increased activity of LDH₁ and LDH₂ Isoenzymes). In recent years, it has been clearly demonstrated that the measurement of myocardial-specific proteins in blood serum (Myoglobin, troponin T, etc.) serves as a highly sensitive early test for myocardial injury.