Which curve represents the behavior of an enzyme

The increase of concentration of these compounds in the blood may be involved in the development of several cardiovascular and renal diseases including volume-expanded hypertension, chronic renal failure, and congestive heart failure [ 24 ]. Natural poisons are a powerful instrument for investigation of enzyme function, and analysis of their action is necessary for these studies.

It might be also a model for design of new inhibitors and activators that will imitate natural compounds with such properties. We have mentioned above nonsteroidal anti-inflammatory drugs that are the inhibitors of cyclooxygenase.

This group of compounds the most prescribed drugs in the world, the oldest among them is aspirin was successfully used for more than one century around the whole world for treatment of patients with fever, cardiovascular diseases, joint pain, etc. Among these drugs are both irreversible and reversible inhibitors that slow down production of prostaglandins that control many aspects of inflammation, smooth muscle contraction, and blood clotting.

But there are many other groups of drugs that are by nature of inhibitors of some enzymes; the following groups of enzyme inhibitors are developed now by pharmaceutical companies and have very important therapeutic significances [ 24 ]. Inhibitors of angiotensin-converting enzyme ACE. ACE catalyzes a conversion of inactive decapeptide angiotensin I into angiotensin II by the removal of a dipeptide from the C-terminus of angiotensin I.

Angiotensin II is a powerful vasoconstrictor. Inhibition of ACE results in the decrease of angiotensin I concentration and in the relaxation of smooth muscles of vessels. Inhibitors of ACE are widely used as drugs for treatment of arterial hypertension [ 25 ]. Proton pump inhibitors PPIs. Proton pump is an enzyme that is located in the plasma membrane of the parietal cells of stomach mucosa.

It is a P-type ATPase that provides proton secretion from parietal cells in gastric cavity against the electrochemical gradient using energy of adenosine triphosphate ATP cleavage. PPIs are groups of substituted benzopyridines that in acid medium of stomach are converted into active sulfonamides interacting with cysteine residues of pump [ 26 ].

Therefore, PPIs are acid-activated prodrugs that are converted into drugs inside the organisms. PPIs are introduced in therapeutic practice in 80th years of the twentieth century. Since this time, the drugs are successfully used for treatment of gastritis, gastric and duodenal ulcer, and gastroesophageal reflux disease.

Statins represent a group of compounds that are analogs of mevalonic acid. They are inhibitors of 3-hydroxymethylglutaryl-CoA reductase, an enzyme participating in cholesterol synthesis.

Statins are used as drugs preventing or slowing the development of atherosclerosis [ 27 ]. Because of the existence of some adverse effects, statins may be recommended for patients that cannot achieve a decrease of cholesterol level in the blood through diet and changes in lifestyle.

Antibiotic penicillin covalently modifies the enzyme transpeptidase, thereby preventing the synthesis of bacterial cell walls and thus killing the bacteria [ 28 ].

Methotrexate is a structural analog of tetrahydrofolate, a coenzyme for the enzyme dihydrofolate reductase, which catalyzes necessarily step in the biosynthesis of purines and pyrimidines. Methotrexate binds to this enzyme approximately fold more tightly than the substrate and inhibits nucleotide base synthesis.

It is used for cancer therapy [ 29 ]. New promising direction of anticancer therapy that is connected with suppression of protein kinases controlling the cellular response to DNA damage is now on the step of development. Selective inhibitors of these enzymes are now being tested in clinical trials in cancer patients [ 30 ]. Breakthrough in treatment of patients with acquired immune deficiency syndrome AIDS that is provoked by human immunodeficiency virus HIV was achieved recently using two different types of enzyme inhibitors.

Nucleoside reverse transcriptase inhibitors and protease inhibitors are now recommended for treatment of patients with this decease. These inhibitors affect also some other viral infections and demonstrated anticancer activity.

Presented here list of enzyme inhibitors that are used in therapy of numerous deceases that is far from being complete. But even mentioned above, points demonstrate how useful and important are therapeutic application of theoretical knowledge obtained as result of study of enzyme inhibitors [ 31 ]. Sciences around the world are involved in a search of new inhibitors of known enzymes that have therapeutic significance.

An example of this complex research is a work devoted to design, synthesis, and study of new inhibitors of carbonic anhydrase, an enzyme that is involved in the development of such symptoms and deceases as edema, glaucoma, obesity, cancer, epilepsy, and osteoporosis see Ref. Enzyme activators are chemical compounds that increase a velocity of enzymatic reaction. Their actions are opposite to the effect of enzyme inhibitors. Among activators we can find ions, small organic molecules, as well as peptides, proteins, and lipids.

Cations can bind not only with enzyme but also with the substrate increasing its affinity to the enzyme that activate enzyme. For example, magnesium ions interact with ATP or with other nucleotides that are negatively charged molecules, decreasing their charge that provides effective binding of nucleotides in substrate binding site of various enzymes and increasing their activity.

In some cases, activation of enzymes is due to the elimination of enzyme inhibitors. In total this effect looks as enzyme activation. Some cations including heavy metal cations inhibit definite enzymes. Special group of activators can produce activation of target enzymes only after the formation of complex with another molecule. This complex, in turn, binds to enzyme and increases the velocity of enzymatic reaction.

The most well-known example of such type of activators is Ca-binding protein calmodulin calcium-modulated protein that is expressed in all eukaryotic cells. Calmodulin is a small protein containing amino acids Its molecule consists of two symmetrical globular domains each with two Ca-binding motifs EF-hand located on N- and C-domains that are jointed by flexible linker.

Flexibility of calmodulin molecule and the presence of nonpolar grooves in the middle part of the protein allow it to bind a large variety of proteins [ 33 ].

Inhibitors and activators modulators that bind to enzymes not in the active site but in special center located far enough from it have name allosteric modulators. Their binding to allosteric sites induces the change of enzyme conformation that affects both the structure of active site and enzyme conformational mobility leading to the decrease or to the increase of enzyme activity.

Just as enzyme active site is specific in relation to substrate, the allosteric site is specific to its modulator [ 16 ]. Many metabolic pathways are regulated through the action of allosteric modulators. Enzymes in metabolic pathways work sequentially, and in such pathways, a product of one reaction becomes a substrate for the next one. The rate of whole pathway is limited by the rate of the lowest reaction. Allosteric regulators often are a final product of whole metabolic pathway 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 AMP , and fructose-2,6-bisphospate that represents positive feedback control.

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. 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. 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 their motifs that participate in the protein-protein interactions in the cell that are important for metabolic regulation.

Among enzyme activators and inhibitors, one can highlight a group of allosteric modulators that participate in feedback regulation of metabolic pathways.

Figure 2 : Diagram of reaction speed and Michaelis-Menten kinetics. For example, by taking the reciprocal of the Michaelis Menten Kinetics Equation, we can obtain the Lineweaver-Burk double reciprocal plot:.

Figure 3. An example of a Lineweaver-Burke plot. This is the rate limiting step. Method 2: The Steady-State Approximation The figure above shows the relatively low and constant concentration of the enzyme-substrate complex due to the complex's slow formation and rapid consumption.

References Chang, Raymond. Physical Chemistry for the Biosciences. Sansalito, CA: University Science, Page Atkins, Peter and de Paula, Julio. Physical Chemistry for the Life Sciences. New York, NY: W.

Freeman and Company, This is at the bottom of the curve. We want to get to the top of the curve. So this would not be the at an optimum rate for trips in To crease at five. It's just a bit better remember here, the optimum ph is six.

We have five. It's going to be too acidic which is going to change the structure and thus the function. Or in this case the optimum uh effectiveness of the protein soup crease perhaps in it for as you can see, definitely not optimum way to basic here. Ah not really even on the curve. So this is definitely not Optimum for peps in at four. We have trips in at eight. Uh So I just I just mentioned the optimum rate. The optimum ph for trips and just eight.

So uh yeah, this is going to make trips in function at an optimal rate. So trips in with eight. And lastly peps in two ph of two that's around here. So definitely not. The optimum rate slightly off from the from the optimum ph and something I want to mention here is that even a small change in BPH is going to drastically differ in the composition of the environment.

So in this case, uh definitely not as many hydrogen ions. Uh and and the reason being is that peach is uh huh. It changed, it changed in a unit of Ph will drastically different.

As I said, the composition of the environment. And so right here, even a difference of 0. So not optimum rate. Um And yeah, I hope this video helped. In chemistry and physics, an element is a substance that cannot be broken down into a simpler substance by chemical means. A pure element is a substance consisting of a single type of atom, with its chemical properties determined by that atom's atomic number, which is the number of protons in its nucleus.

Examples of elements include carbon, oxygen, aluminum, iron, gold, copper, mercury, and lead. In biology, the elements of life are the essential building blocks that make up living things.

They are carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur. The first four of these are the most important, as they are used to construct the molecules that are necessary to make up living cells.