**Author details**

that activates enzymes catalyzing a limiting step of the whole pathway. Enzymes in a metabolic pathway can be inhibited or activated by downstream products. This regulation represents negative and positive feedbacks that slow metabolic pathway when the final product is produced in large amounts or accelerate it when a final product is presented in low concentration. Therefore, allosteric modulators are important participants of such negative and positive feedbacks in metabolic pathways or between them making metabolism self-controlled.

For example, ATP and citrate are inhibitors of phosphofructokinase that is a key enzyme of glycolytic pathway. One product of glycolysis is ATP. Another product is pyruvate that after the conversion into acetyl-CoA is condensed with citrate opening cycle of citrate acids (Krebs cycle). Reactions of this cycle produce reduced nicotinamide adenine dinucleotide reduced (NADH) and flavinadeninidinucleotide reduced (FADH2), oxidation of which is coupled with massive production of ATP in mitochondria. Availability of ATP or citrate inhibits glycolysis preventing glucose oxidation (negative feedback). Inhibition of phosphofructokinase by ATP or by citrate occurs by allosteric manner [35]. Described negative feedback control maintains a steady concentration of ATP in the cell. It should be noted also that metabolic pathways are regulated not only through inhibition but also through activation of the key enzymes. Mentioned above phosphofructokinase is activated by adenosine diphosphate (ADP), adenosine monophosphate

Enzymes that are regulated by allosteric modulators are usually presented by several interacting subunits (they are called oligomers). A very interesting example of regulation of the activity of oligomeric enzymes is c-AMP-dependent protein kinase that is an important regulatory enzyme participating in the phosphorylation of serine and threonine residues of target proteins changing by this way their activity. This enzyme consists of four subunits; two of them are catalytic and two are regulatory. Cyclic AMP (c-AMP) is allosteric activator of this enzyme. Catalytic subunit being bound to the regulatory one is inactive. Binding of two c-AMP molecules to allosteric sites of each regulatory subunit induces their conformation transition that results in dissociation of the tetrameric complex and in activation of catalytic subunits [36]. Decrease of c-AMP concentration leads to its dissociation from the allosteric site and to association of regulatory and catalytic subunits with subsequent inactivation of catalytic subunits. By this way, c-AMP activity depends upon the c-AMP concentration in the cell.

Enzyme inhibitors and activators are a number of various chemical compounds that can slow down (or even stop) and activate enzymes, natural protein catalysts. They include inorganic compounds (often anions), different organic compounds (mainly containing reactive groups that can modify amino acids of protein), natural proteins, lipids, and carbohydrates. Mechanism of inhibitor and activator action on the enzyme activity includes a step of their binding to the enzyme, after which a step of the change of enzyme conformation often follows. Inhibitors are a good tool for study of enzyme reaction mechanisms. Many natural inhibitors especially obtained from plants and invertebrates often imitate natural proteins or some of

(AMP), and fructose-2,6-bisphospate that represents positive feedback control.

**4. Conclusions**

254 Enzyme Inhibitors and Activators

Olga D. Lopina

Address all correspondence to: od\_lopina@mail.ru

Department of Biochemistry, School of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia
