Biochemical Basis of Human Body Functioning - Volkov N.I., Nesen E.N. 2000

Biochemical Basis of Human Body Functioning
Enzymes: Biological Catalysts
Factors Affecting Enzyme Activity

The rate of biochemical reactions, determined by The change in the concentration of reactants or products per unit of time, depends on enzyme activity and reaction conditions. Each enzyme has its own optimal conditions for activity. Optimal conditions are defined as those under which the enzymatic reaction proceeds at its maximum rate. The Rate of Enzymatic reactions is influenced by: Enzyme Concentration; Substrate Concentration; pH of the medium; Temperature; and the presence of activators and inhibitors.

Enzyme and substrate concentration. The rate of an enzymatic reaction increases with an increase in enzyme concentration at high substrate concentrations (Fig. 38, a). In the body at relative rest, many Enzymes do not exhibit maximum activity due to low concentrations of their substrates. During muscular activity, METABOLISM/26.html">Energy Metabolism increases and the substrates of many reactions accumulate, which helps to increase The activity of many enzymes.

At a constant enzyme concentration, the rate of an enzymatic reaction increases with increasing substrate concentration until the enzyme is saturated with the substrate, reaching a maximum velocity (V_max) beyond which it does not increase (Fig. 38, b). Each enzymatic reaction is characterized by the Michaelis constant (K_m), defined as the substrate concentration at which the reaction rate is half of the maximum. The values of V_max and K_m are used to characterize the catalytic capacity of enzymes.

pH of the medium. Each enzyme has a narrow range of pH values at which its activity is maximal. Most enzymes exhibit maximum activity in the body at pH values close to 7.0, i.e., in a neutral medium (Fig. 39). However, certain enzymes show high activity in a highly acidic medium, such as Pepsin (pH 2.0) and sucrase (pH 4.5), or in an alkaline medium, such as Trypsin (pH 8.0), lipase (pH 9.0), and arginase (pH 9.7).

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Fig. 38 Effect of Substrate concentration on enzyme activity

Fig. 39 Effect of pH on enzyme activity (a); pH optimum (b) for the enzymes pepsin (1), trypsin (2), and alkaline phosphatase (3)

The Effect of pH on enzyme activity is associated with Changes in the degree of ionization of their protein molecule under The Influence of protons H⁺ or hydroxyls (OH^-), which primarily affects The Structure of the Active Site of the enzyme.

In The Human Body at relative rest, the range of pH fluctuations is negligible, and enzymes "work" under their optimal conditions. During intense physical exertion, lactic acid accumulates in the Muscles, which can acidify the environment and reduce the activity of many enzymes.

Temperature. As temperature increases from 0 to 40 °C, enzyme activity generally increases (Fig. 40). The temperature coefficient Q₁₀ = 2, indicating a twofold increase in the rate of the enzymatic reaction for every 10 °C change in temperature. A further increase in temperature to 45–55 °C leads to a sharp decrease in enzyme activity due to thermal Denaturation of the protein. All enzymes have their own optimal temperature at which their activity is maximal (for many enzymes, the optimal temperature is 37–40 °C). However, There are also thermostable enzymes, such as myokinase, which retains its activity when heated to 100 °C. As temperature decreases, enzyme activity drops. Nevertheless, irreversible denaturation does not occur, as their activity is restored under optimal temperature conditions (hibernation in animals is an example of this). This property of enzymes is utilized in freezing food products, as well as Organs and genetic material used for transplantation.

Activators and inhibitors. Enzymes are typically regulated by specific low-molecular-weight substances and Metal Ions, which are called effectors, modulators, or regulators of enzymes. Some of these can decrease enzyme activity (inhibitors), while others can increase it (activators). This mechanism of controlling enzyme activity is widely studied because of its great practical significance.

A wide variety of substances can act as activators. These are primarily divalent metal ions, such as Mg²⁺, Zn²⁺, Mn²⁺, Co²⁺, Cu²⁺, Fe²⁺, and Ca²⁺. They cause a reversible change in the STRUCTURE OF THE active site. For example, Carbonic anhydrase is activated by Zn²⁺ ions, creatine kinase by Mg²⁺ ions; Muscle Myosin ATPase is activated by Ca²⁺ ions, and Cu²⁺ and Fe²⁺ ions are required for the catalytic activity of Respiratory Chain enzymes.

Fig. 40 Effect of temperature on enzyme activity

Fig. 41 Schematic of competitive inhibitor action

The activation of some enzymes can occur through modification of their molecule without affecting the enzyme's active site. For example, HCl activates gastric pepsinogen, converting it from an inactive form to an active one (pepsin). Pancreatic lipase is activated by Bile acids.

Inhibitors are often substances structurally similar to substrates that bind to the active site of the enzyme. Inhibition can be reversible or irreversible. In reversible inhibition, the inhibitor easily dissociates from the enzyme, and enzyme activity is restored. In irreversible inhibition, the inhibitor binds tightly to the enzyme and blocks substrate access to the active site.

The process of inhibition is widely used to modulate metabolic processes in medicine and other fields of human activity. The therapeutic effect of A number of drugs is due to their inhibitory action on specific enzymes. Among inhibitors that reversibly inhibit enzymes, a distinction is made between Competitive and non-Competitive Inhibitors.

Competitive inhibitors have a structure similar to the substrate and compete with it for the binding site in the active site of the enzyme. As seen in Fig. 41, in the case of competitive inhibition, the inhibitor (I) binds to the enzyme at the same site as the substrate, As a result of which the substrate can no longer bind to the enzyme. Competitive inhibition is reversible and depends on the concentration of the inhibitor and substrate. At high substrate concentrations, such inhibitors are ineffective.

Non-competitive inhibitors do not react with the active site of the enzyme, but with another part of its molecule. This causes A change in the structure of the active site, which disrupts the catalytic process. The action of such inhibitors can only be reversed by chemically changing the structure of their molecule. Non-competitive inhibitors include heavy metal ions and their Organic compounds (mercury, lead, arsenic, and many poisons) that can block SH-groups in the enzyme and disrupt or completely suppress metabolic processes in the body.