Textbook - BIOLOGICAL CHEMISTRY - Gubsky Yu.I. - 2000

Chapter VI. BIOCHEMISTRY OF PHYSIOLOGICAL FUNCTIONS AND SPECIALIZED TISSUES

CHAPTER 32. BIOCHEMISTRY OF MUSCLES AND MUSCULAR CONTRACTION

Muscles are a molecular system responsible for transforming the chemical energy of ATP into the mechanical energy of contraction and movement. Based on their structural Organization, Human and Animal muscles are classified into skeletal (striated), smooth, and cardiac Muscle.

All types of cellular movement in eukaryotes (ranging from Yeast to humans) are based on the interaction and mutual sliding of filaments formed by the Proteins Actin and Myosin. Non-muscular movements include amoeboid locomotion of leukocytes, macrophages, fibroblasts, spermatozoa, and other Cells, as well as Intracellular Movements such as chromosome segregation, endocytosis, and exocytosis. The motility of Cilia and flagella is driven by the interaction of another pair of proteins: dynein and tubulin.

The biochemical processes underlying skeletal Muscle contraction are the most thoroughly studied.

32.1. ULTRASTRUCTURE AND CHEMICAL COMPOSITION OF MUSCLES

The structural unit of Skeletal Muscle is a multinucleated Cell known as a myocyte, or muscle fiber, which in humans can reach lengths of 10-12 cm and diameters of 0.01-0.1 mm.

Class="center">Ultrastructural components of myocytes

Myocytes are surrounded by an electrically excitable Plasma Membrane called the sarcolemma and contain a cytosolic compartment (sarcoplasm), contractile elements (myofibrils), a highly differentiated Endoplasmic reticulum (sarcoplasmic reticulum), and a well-developed system of Mitochondria, or sarcosomes (Fig. 32.1).

Fig. 32.1. Ultrastructure of skeletal muscle.

In actively functioning human skeletal muscles, mitochondria are very numerous; they are located along the myofibrils in close proximity to them, which ensures a minimal diffusion distance for high-energy phosphates to the contractile elements.

Skeletal muscles possess a well-developed system of membranes and tubules of the sarcoplasmic reticulum (SR), which serves as the primary reservoir for intracellular Ca²⁺, controlling the active concentration of Calcium Ions in the Cytosol. Changes in cytosolic Ca²⁺ concentration act as a biochemical switch triggering muscle contraction. The elements of the SR are in contact with a system of transverse tubules, known as the T-system, along which electrical potentials propagate from the sarcolemma to the SR membranes, inducing the release of calcium ions from the SR.

A significant portion of the muscle cell volume is occupied by contractile elements, the myofibrils, which are packed into parallel bundles. The Molecular Basis of myofibrils consists of contractile proteins organized into thread-like structures (filaments) known as actin and myosin.

Sarcomeres are the Structural and functional units of the skeletal muscle contractile apparatus. Sarcomeres are formed by bundles of myofibrils separated from one another by perpendicular lines called Z-lines.

Electron microscopic studies of sarcomeres have revealed ordered structures that create the characteristic cross-striation of skeletal muscles (Fig. 32.2), specifically:

I-bands (isotropic), formed by "thin" myofibrillar filaments (about 6 nm in diameter);

A-bands (anisotropic), formed by "thick" myofibrillar filaments (15-17 nm in diameter) that overlap with the "thin" filaments;

H-zone, the region within the A-band where thick filaments do not overlap with thin filaments.

Fig. 32.2. Structural organization of myofibril sarcomeres.

Biochemical Composition of muscles

Mammalian skeletal muscles contain: 72-80% Water; 16-20% proteins; 0.9-2.2% non-protein nitrogenous compounds (creatine, creatine phosphate, ATP, ADP, Amino Acids, etc.); non-nitrogenous Organic compounds (Glycogen, 0.3-3.0%; Phospholipids, 0.4-1.0%; Cholesterol, 0.06-0.2%); mineral elements (K⁺, Ca²⁺, Na⁺, etc.).

Muscle Proteins

Skeletal muscle proteins consist of water-insoluble myofibrillar proteins (accounting for 75-80% of the total muscle protein content) and water-soluble sarcoplasmic proteins, known as myogen.

The myogen fraction predominantly comprises Enzymes that catalyze catabolic reactions providing the Bioenergetics of muscle contraction—such as Glycogen phosphorylase, glycolytic enzymes, creatine phosphokinase, adenylate kinase, and the oxygen-storing protein Myoglobin. The sarcosomes contain enzymes of The Tricarboxylic Acid Cycle, Biological Oxidation, and Oxidative Phosphorylation.

Myofibrillar proteins

Myofibrils are composed of the following proteins:

1) in thick filaments—the protein myosin;

2) in thin filaments—the proteins actin, Tropomyosin, and the troponin complex (troponin T, troponin I, troponin C);

3) the protein α-actinin—a component of the Z-line of sarcomere; the ends of the F-actin molecules of the thin filaments are attached to this protein.

Table 32.1. Protein composition of skeletal muscle (adapted from J. Musil et al., 1980, with modifications)

Myosin is a fibrillar protein that forms the thick filaments of myofibrils. The myosin molecule is asymmetric, consisting of two heavy polypeptide chains with an α-helical conformation twisted around each other; the molecular length is 160 nm. The N-termini of the heavy chains form globular "heads" that are noncovalently attached to four additional light polypeptide chains.

Under conditions of tryptic Hydrolysis, myosin is cleaved into two fragments—meromyosins: light meromyosin (LMM) and heavy meromyosin (HMM). Further hydrolysis of HMM by Papain results in The formation of two identical globular subfragments S1 (myosin heads) and a rod-like subfragment S2 (Fig. 32.3).

The S1 heads contain catalytic centers with ATPase activity and actin-binding sites (in the absence of ATP).

Fig. 32.3. Structure OF THE myosin molecule.

The fibrillar "tails" of myosin molecules contact each other longitudinally, forming the thick filaments of sarcomeres, each comprising about 400 myosin molecules. The globular heads protrude from the outer surface of the filament (Fig. 32.4).

Fig. 32.4. Molecular organization of the thick (myosin) filament.

Actin is a protein that exists in two forms: G- and F-actin. G-actin is a globular protein consisting of sphere-like molecules with a diameter of about 5 nm. G-actin molecules (subunits) noncovalently associate with one another to form bead-like structures—chains of fibrillar F-actin.

In muscle cells, F-actin is represented by fibrillar structures consisting of two chains intertwined around each other (Fig. 32.5):

Fig. 32.5. Actin filament: a — electron micrograph; b — diagram of the formation of double-helical F-actin chains from G-actin.

F-actin forms the structural backbone of the thin filaments in sarcomeres. Within thin filaments, F-actin chains are associated with tropomyosin and troponins.

Tropomyosin consists of elongated protein molecules composed of two polypeptide chains (α and β) that form a double helix. These rod-like tropomyosin molecules (40 nm long and 2 nm thick) lie in the grooves between the two F-actin chains in such a way that each tropomyosin molecule contacts seven G-actin molecules (subunits).

Troponin is a protein of the thin filaments composed of three subunits: TnT, TnI, and TnC. Troponin complexes have a globular shape and are located along the actin filament at intervals of 38.5 nm, contacting the ends of the tropomyosin molecules (Fig. 32.6).

Fig. 32.6. Interaction scheme of tropomyosin (Tm) and troponins with actin: a — F-actin helix, b — interaction of Tm and troponins with G-actin subunits.

The most extensively studied component of the troponin complex is TnC, a calcium-binding protein structurally and functionally similar to calmodulin, a universal transducer of calcium signals in biochemical systems. The TnI protein interacts with actin, while TnT ensures the interaction of the troponin complex with tropomyosin.