Regulation of enzyme activity and their methods

Being a unit of living matter, functioning as a complex of open biosystems, the cell constantly exchanges substances and energy with the external environment. To maintain homeostasis in it, there is a group of special substances of protein nature - enzymes. The structure, functions, and regulation of enzyme activity are studied by a special branch of biochemistry, called enzymology. In this article, on specific examples, we will consider various mechanisms and methods for regulating enzyme activity that are inherent in higher mammals and humans.

Conditions necessary for optimal enzyme activity

Biologically active substances that selectively affect both the assimilation reaction and the cleavage show their catalytic properties in cells under certain conditions. For example, it is important to find out in which part of the cell the chemical process takes place , in which enzymes participate. Due to compartmentalization (cytoplasmic division into sections), antagonistic reactions occur in its various parts and organoids.

Thus, the synthesis of proteins is carried out in the ribosomes, and their splitting - in the hyaloplasm. Cellular regulation of the activity of enzymes catalyzing the opposite biochemical reactions provides not only the optimal rate of metabolism, but also prevents the formation of energy-useless metabolic pathways.

Multienzyme complex

The structural and functional organization of enzymes forms the enzymatic apparatus of the cell. Most of the chemical reactions that occur in it are interrelated. If in a multi-stage chemical process the product of the first reaction is a reagent for the subsequent reaction, in this case the spatial arrangement of the enzymes in the cell is particularly pronounced.

It must be remembered that enzymes are by their nature simple or complex proteins. And their sensitivity to the cellular substrate is primarily due to a change in the spatial configuration of the tertiary or quaternary structure of the peptide. Enzymes also react to changes not only within cellular parameters, such as the chemical composition of the hyaloplasm, the concentration of reagents and reaction products, temperature, but also changes occurring in neighboring cells or in the intercellular fluid.

Why is the cell divided into compartments

The reasonableness and logic of the arrangement of living nature is simply amazing. This fully applies to the life manifestations characteristic of the cell. For a scientist-chemist it is perfectly clear that multidirectional enzymatic chemical reactions, for example, synthesis of glucose and glycolysis, can not proceed in the same tube. How, then, do the opposite reactions occur in the hyaloplasm of one cell, which is the substrate for their conduct? It turns out that the cellular contents - cytosol, - in which antagonistic chemical processes are carried out, is spatially separated and forms isolated loci - compartments. Thanks to them, the metabolic reactions of higher mammals and humans are regulated particularly accurately, and the metabolic products are converted into forms that freely penetrate through the septal partitions. Then they restore their original structure. In addition to cytosol, enzymes are found in organelles: ribosomes, mitochondria, nucleus, lysosomes.

The role of enzymes in energy metabolism

Consider the oxidative decarboxylation of pyruvate. Regulation of catalytic activity of enzymes in it is well studied by enzymology. This biochemical process takes place in the mitochondria, the dual-membrane organelles of eukaryotic cells, and is an intermediate process between anoxic glucose cleavage and the Krebs cycle. Pyruvate dehydrogenase complex - PDH - contains three enzymes. In higher mammals and humans, its decrease occurs with an increase in the concentration of Acetyl-CoA and NATH, that is, in the case of the appearance of alternative possibilities for the formation of Acetyl-CoA molecules. If the cell requires additional energy and requires new acceptor molecules to enhance the reactions of the tricarboxylic acid cycle, the enzymes are activated.

What is allosteric inhibition

Regulation of enzyme activity can be carried out by special substances - catalytic inhibitors. They can covalently bind to specific loci of the enzyme, bypassing its active center. This leads to deformation of the spatial structure of the catalyst and automatically leads to a decrease in its enzymatic properties. In other words, allosteric regulation of enzyme activity occurs. We also add that such a form of catalytic action is inherent in oligomeric enzymes, that is, those whose molecules consist of two or more polymeric protein subunits. The PDH complex considered in the previous chapter contains exactly three oligomeric enzymes: pyruvate dehydrogenase, dehydrolipoyl dehydrogenase and hydrolylipoyl transacetylase.

Regulatory enzymes

Studies in enzymology have established the fact that the rate of chemical reactions depends both on the concentration and the activity of the catalyst. Most often, metabolic pathways contain the main enzymes that regulate the rate of reactions in all its parts.

They are called regulatory and usually affect the initial reactions of the complex, and can also participate in the slowest chemical processes in irreversible reactions, or they join the reagents at the branch points of the metabolic pathway.

How is peptide interaction carried out?

One of the ways by which the regulation of the activity of enzymes in the cell occurs is the protein-protein interaction. What are we talking about? The addition of regulatory proteins to the enzyme molecule is realized, as a result of which their activation takes place. For example, the enzyme adenylate cyclase is located on the inner surface of the cell membrane and can interact with structures such as the hormone receptor, as well as with the peptide located between it and the enzyme. Since the intermediate protein changes its spatial confirmation as a result of the combination of the hormone and the receptor, this method of enhancing the catalytic properties of adenylate cyclase in biochemistry is called "activation due to the attachment of regulatory proteins."

Protomers and their role in biochemistry

This group of substances, otherwise called protein kinases, will accelerate the transfer of the anion PO ₄ ^3- to the hydroxo group of the amino acids entering the peptide macromolecule. The regulation of the activity of enzymes of protomers will be considered by us with the example of protein kinase A. Its molecule, the tetramer, consists of two catalytic and two regulatory peptide subunits and does not function as a catalyst until four molecules of cAMP are attached to the regulatory regions of the protomer. This causes a transformation of the spatial structure of the regulatory proteins, which leads to the release of two activated catalytic protein particles, that is, the dissociation of protomers occurs. If cAMP molecules are separated from the regulatory subunits, the inactive protein kinase complex is again restored to the tetramer, since the association of catalytic and regulatory peptide particles occurs. Thus, the ways of regulating enzyme activity considered above ensure their reversible character.

Chemical regulation of enzyme activity

Biochemistry has also studied such mechanisms for the regulation of enzyme activity, such as phosphorylation, dephosphorylation. The mechanism of regulation of enzyme activity in this case has the following form: the amino acid residues of the enzyme containing OH ^- groups change their chemical modification due to the influence of phosphoprotein phosphatases on them. In this case, the correction is given to the active center of the enzyme, and for some enzymes this is the cause that activates them, and for others - the inhibitor. In turn, the catalytic properties of the phosphoprotein phosphatases themselves are regulated by hormone. For example, animal starch - glycogen - and fat in the intervals between meals are split in the gastrointestinal tract, more precisely, in the duodenum under the influence of glucagon - a pancreatic enzyme.

This process is enhanced by the phosphorylation of trophic gastrointestinal enzymes. In the period of active digestion, when food comes from the stomach into the duodenum, the synthesis of glucagon is enhanced. Insulin - another enzyme of the pancreas, produced by the alpha cells of the islets of Langerhans - interacts with the receptor, including the mechanism of phosphorylation of the same digestive enzymes.

Partial proteolysis

As we see, the levels of regulation of enzyme activity in the cell are varied. For enzymes that are outside the cytosol or organoids (in the blood plasma or in the gastrointestinal tract), the process of their activation is the process of hydrolysis of CO-NH peptide bonds. It is necessary, since such enzymes are synthesized in an inactive form. From the enzyme molecule, the peptide part is cleaved, and the active center is subjected to the remaining structure of the modification. This leads to the fact that the enzyme "enters the working state", that is, it becomes capable of influencing the course of the chemical process. For example, an inactive pancreatic enzyme, trypsinogen, does not break down the food proteins that enter the duodenum. It undergoes proteolysis under the action of enteropeptidase. After that, the enzyme is activated and is now called trypsin. Partial proteolysis is a reversible process. It occurs in such cases as the activation of enzymes that cleave polypeptides in blood clotting processes.

The role of the concentration of the initial substances in the metabolism of the cell

The regulation of the activity of the enzyme by the accessibility of the substrate was partially examined by us in the subheading "Multienzyme complex". The rate of catalytic reactions passing through several stages strongly depends on how many molecules of the initial substance are in the cell's hyaloplasm or organelles. This is due to the fact that the metabolic pathway is directly proportional to the concentration of the starting material. The more molecules of the reagent is in the cytosol, the higher the rate of all subsequent chemical reactions.

Allosteric Regulation

Enzymes, the activity of which is controlled not only by the concentration of the initial reagent substances, but also by the effectors, the so-called allosteric regulation is inherent. Most often, such enzymes are represented by intermediate products of metabolism in the cell. Thanks to the effectors, the activity of the enzymes is regulated. Biochemistry has proved that such compounds, called allosteric enzymes, are very important for cell metabolism, since they have an extremely high sensitivity to changes in its homeostasis. If the enzyme inhibits the chemical reaction, that is, reduces its speed - it is called a negative effector (inhibitor). In the opposite case, when there is an increase in the reaction rate, it is an activator, a positive effector. In most cases, the starting materials, that is, the reagents entering into the chemical interactions, play the role of activators. Finite, products, formed as a result of multistage reactions, behave as inhibitors. This kind of regulation, built on the relationship between the concentration of reagents and products, is called heterotrophic.