Biochemical Foundations of Human Vital Activity - Volkov, N.I., Nesen, E.N. 2000

Biochemical Foundations of Human Vital Activity
Biochemistry of Proteins
Characteristics of Specific Proteins Involved in Ensuring Muscular Activity

Contractile Proteins. Cells of skeletal Muscles and other Tissues responsible for movement contain contractile proteins—Myosin and Actin (see Chapter 14).

Myosin is a high-molecular-weight fibrillar protein with a Molecular Weight of 490,000. The fibrillar myosin filament is quite long (about 160 nm) and heterogeneous. It features a globular HEAD and a long tail composed of two polypeptide chains twisted around each other into a double helix (Fig. 90, a). The head has a globular shape and protrudes from the main body of the protein, bearing binding sites for actin and ATP. Part of the myosin molecule in the head region exhibits adenosine triphosphatase (ATPase) enzymatic activity, capable of cleaving ATP into ADP and phosphate (H₃PO₄) with the release of energy. The long "tail" of the myosin molecule consists of light (1) and heavy (2) meromyosin. The latter contains flexible hinge regions that play a crucial role in The formation of thick myosin filaments in myofibrils and in Muscle contraction. Numerous myosin molecules form thick filaments in the myofibrils of skeletal muscles.

Actin is a high-molecular-weight protein with a molecular weight of 46,000. It exists in two forms: globular (G-actin) and fibrillar (F-actin). These forms of actin are interconvertible (Fig. 90, b). G-actin is capable of firmly binding Ca²⁺ ions and a single molecule of ATP or ADP. Upon cleaving ATP, G-actin polymerizes into a fibrillar Structure. This transition takes place in the presence of K⁺ and Mg²⁺ ions.

In skeletal muscles, the fibrillar form of actin forms a double-stranded twisted filament, which serves as the backbone of the thin filament in myofibrils.

Connective Tissue proteins. Connective tissue (tendons, ligaments, the organic matrix of bones, Cartilage, subcutaneous adipose tissue, the Cytology/practical/76.html">Cornea of the eye, etc.) performs structural and supportive Functions, integrates cells into specific structures, and provides them with strength and elasticity, which plays a major role in muscular activity. Its main components are the proteins Collagen and Elastin.

Collagen is the most abundant fibrillar protein in the body. It comprises an entire family of structurally complex proteins with diverse functions; therefore, it is more accurate to refer to them as collagens. Collagens have a high molecular weight (approximately 300,000), are insoluble in Water, and possess high tensile strength. Collagen fibrils can withstand loads 10,000 times greater than their mass and exceed the strength of steel wire of the same diameter. A key characteristic of collagens is their inability to stretch.

The remarkable strength and Other properties of collagens are related to the Structural Features of their molecules—tropocollagens. Each collagen molecule consists of three polypeptide chains twisted together like a three-strand rope (Fig. 91, a). Numerous collagen molecules assemble into parallel, repeating, staggered bundles to form collagen fibrils (Fig. 91, b). Cross-Hydrogen Bonds exist between individual fibrils, resulting in virtually inextensible fibers (Fig. 91, c). With advancing age, the number of cross-links in collagen fibers increases, leading to greater stiffness and brittleness of bones and tendons, as well as a decrease in the transparency of the eye cornea.

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Fig. 90 Structure of myosin (a) and actin (b)

Fig. 91 Structure of a collagen molecule (a), collagen fibrils (b), connective tissue collagen fibers (c), and an elastin molecule (d)

The collagen molecule is rich in two major Amino Acids—Glycine and Alanine—as well as two minor ones, 4-hydroxyproline and 5-hydroxylysine. Glycine occupies every third position in the polypeptide chain of the protein and plays a vital role in collagen function. Consequently, an adequate supply of this amino acid in the body is essential. The strength of collagen fibers depends on the presence of Vitamin C (ascorbic acid) in tissues, which participates in collagen formation.

Elastin is abundant in ligaments, the walls of large Blood Vessels—particularly the aorta—and other elastic tissues. It has a lower molecular weight (approximately 72,000) and a specific fibrillar structure.

Elastin fibrils consist of tropoelastin subunits cross-linked together to form a highly resilient network (see Fig. 91, d). Owing to the specific arrangement of polypeptide chains involving The amino acid desmosine, elastin fibers can stretch several-fold and return to their original length upon load removal. Differences in the Physical Properties of elastin and collagen stem from the unique features of their Amino acid sequences.

Oxygen-carrier proteins. In the course of evolution, living organisms developed specialized oxygen-carrying molecules that bind and deliver oxygen to the cells of various Organs, where it is utilized in Biological Oxidation. In The Human Body, Hemoglobin and Myoglobin serve as the primary oxygen carriers.

Hemoglobin is located in red Blood Cells (erythrocytes) and transports oxygen from the Lungs to tissues, and carbon dioxide from tissues to the lungs. It is also capable of binding hydrogen ions (H⁺) to maintain a constant active reaction environment within erythrocytes, thus acting as an intracellular buffer.

The hemoglobin molecule features a quaternary structure composed of four protein subunits: two a subunits (a₁ and a₂) and two β subunits (β₁ and β₂). Each subunit has a characteristic tertiary structure and a non-protein moiety (Fig. 92). The non-protein component of hemoglobin is called heme, and the protein component is globin. Heme contains four pyrrole rings coordinated at the center with an iron atom. The iron in heme can exist in the ferrous (Fe²⁺) or ferric (Fe³⁺) state and enables the binding of oxygen (O₂). Only divalent iron is capable of binding oxygen. The presence of heme imparts a red color to these proteins, while globin ensures the species Specificity of hemoglobin.

In the lungs, hemoglobin (Hb) interacts with oxygen to form oxyhemoglobin,

or the protonated form of hemoglobin

Hemoglobin binds both oxygen and hydrogen ions (H⁺) at different sites on its molecule. The binding of oxygen by hemoglobin depends on the concentration of oxygen and H⁺ ions in the medium. At high oxygen partial pressure and the higher pH characteristic of lung tissues, hemoglobin rapidly binds oxygen and releases hydrogen ions. Conversely, at low oxygen partial pressure (in peripheral tissues) and low blood pH, hemoglobin releases oxygen and binds H⁺ protons, functioning as a buffer.

In tissues, hemoglobin binds carbon dioxide (CO₂) via the protein portion of its molecule, resulting in the formation of carbaminohemoglobin:

Fig. 92 Structure of hemoglobin (a), its subunit (b), and The structure of heme (a)

This form of hemoglobin delivers СO₂ to the lungs and facilitates its elimination from the body. The binding of СO₂ to the protein molecule decreases the affinity of heme for O₂ and promotes the release of oxygen in tissues. Consequently, hemoglobin is capable of binding and co-transporting gases (O₂, СO₂) and H⁺ ions, which is of paramount importance for the METABOLISM/26.html">Energy Metabolism of all human body cells.

The iron in hemoglobin can tightly bind a carbon monoxide (CO) molecule to form carboxyhemoglobin (НbСО):

In this state, hemoglobin is unable to bind and transport oxygen. This leads to oxygen deprivation (Hypoxia) in the body, which can be fatal.

The blood of an adult male contains 14–18 g of hemoglobin per 100 ml of blood, and in women, 12–16 g. Each gram of Hb can bind 1.34 ml of O₂. On average, 1 liter of blood contains 160 g of Hb. This amount of hemoglobin determines the oxygen capacity of the blood, averaging 22 ml of O₂ per 100 ml of blood.

Myoglobin is an oxygen-transport protein found primarily in slow-twitch muscle fibers, giving them their red color. It consists of a single polypeptide chain, similar to a hemoglobin subunit, and a non-protein moiety—the heme (Fig. 93).

Fig. 93 Structure of myoglobin

Myoglobin binds oxygen more readily than hemoglobin and transports it to the sites of utilization—the Cell/35.html">Mitochondria. Muscles absorb oxygen from the blood and store it as oxymyoglobin. Thus, myoglobin creates an oxygen reserve in muscles, which is utilized to enhance oxidative processes, such as during physical exertion. In humans and higher terrestrial animals, myoglobin binds only about 14% of the oxygen transported by the blood, whereas in aquatic animals (e.g., seals), myoglobin binds approximately 40% of all oxygen present in the animal's body.