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Enzymes are biological catalysts that accelerate chemical reactions by lowering the activation energy. Enzymes bind to substrates and catalyze reactions in four different ways: bringing substrates together in an optimal orientation, compromising the bond structures of substrates so that bonds can be more easily broken, providing optimal environmental conditions for a reaction to occur, or participating directly in their chemical reaction by forming transient covalent bonds with the substrates.
Enzyme action must be regulated so that in a given cell at a given time, the desired reactions are being catalyzed and the undesired reactions are not. Enzymes are regulated by cellular conditions, such as temperature and pH. They are also regulated through their location within a cell, sometimes being compartmentalized so that they can only catalyze reactions under certain circumstances. Inhibition and activation of enzymes via other molecules are other important ways that enzymes are regulated. Inhibitors can act competitively, noncompetitively, or allosterically; noncompetitive inhibitors are usually allosteric. Activators can also enhance the function of enzymes allosterically. The most common method by which cells regulate the enzymes in metabolic pathways is through feedback inhibition. During feedback inhibition, the products of a metabolic pathway serve as inhibitors (usually allosteric) of one or more of the enzymes (usually the first committed enzyme of the pathway) involved in the pathway that produces them.
A substance that helps a chemical reaction to occur is a catalyst, and the special molecules that catalyze biochemical reactions are called enzymes. Almost all enzymes are proteins, made up of chains of amino acids, and they perform the critical task of lowering the activation energies of chemical reactions inside the cell. Enzymes do this by binding to the reactant molecules, and holding them in such a way as to make the chemical bond-breaking and bond-forming processes take place more readily. It is important to remember that enzymes don’t change the ∆G of a reaction. In other words, they don’t change whether a reaction is exergonic (spontaneous) or endergonic. This is because they don’t change the free energy of the reactants or products. They only reduce the activation energy required to reach the transition state.
Figure 1: Enzymes lower the activation energy of the reaction but do not change the free energy of the reaction. Here the solid line in the graph shows the energy required for reactants to turn into products without a catalyst. The dotted line shows the energy required using a catalyst. This figure should say Gibbs Free Energy on the Y-axis and instead of noting deltaH should have deltaG. Attribution: Marc T. Facciotti (own work)
Enzyme Active Site and Substrate Specificity
The chemical reactants to which an enzyme binds are the enzyme’s substrates. There may be one or more substrates, depending on the particular chemical reaction. In some reactions, a single-reactant substrate is broken down into multiple products. In others, two substrates may come together to create one larger molecule. Two reactants might also enter a reaction, both become modified, and leave the reaction as two products. The location within the enzyme where the substrate binds is called the enzyme’s active site. The active site is where the “action” happens, so to speak. Since enzymes are proteins, there is a unique combination of amino acid residues (also called side chains, or R groups) within the active site. Each amino acid side-chain is characterized by different properties. Amino acids can be classified as large or small, weakly acidic or basic, hydrophilic or hydrophobic, positively or negatively charged, or neutral. The unique combination of amino acids, their positions, sequences, structures, and properties, creates a very specific chemical environment within the active site. This specific environment is suited to bind, albeit briefly, to a specific chemical substrate (or substrates). Due to this jigsaw puzzle-like match between an enzyme and its substrates (which adapts to find the best fit between the transition state and the active site), enzymes are known for their specificity. The “best fit” between an enzyme and its substrates results from the their respective shapes and the chemical complementarity of the functional groups on each binding partner.
Figure 2: This is an enzyme with two different substrates bound in the active site. The enzymes are represented as blobs, except for the active site which shows the three R-groups of each of the three amino acids located in the active site. These R groups are interacting with the substrates through hydrogen bonding (represented as dashed lines)
At this point in the class you should be familiar with all the types of bonds as well as the chemical characteristics of all the functional groups. For example, the R group of R180 in the enzyme depicted above is the amino acid Arginine (abbreviated as R) and has an R group that consists of several amino functional groups. Amino functional groups contain a nitrogen (N) and hydrogen (H) atoms. Nitrogen is more electronegative than hydrogen so the covalent bond between N-H is a polar covalent bond. The hydrogen atoms in this bond will have a positive dipole moment, and the nitrogen atom will have a negative dipole moment. This allows amino groups to form hydrogen bonds with other polar compounds. Likewise, the backbone carbonyl oxygens of Valine (V) 81 and Glycine (G) 121 the backbone amino hydrogen of V81 are depicted engaged in hydrogen bonds with the small molecule substrate.
Prepare for the Test
Look to see which atoms in the figure above are involved in the hydrogen bonds between the amino acid R groups and the substrate. You will need to be able to identify these on your own, hydrogen bonds may not be drawn in for you on the test.
If you changed the pH of the solution that this enzyme was located in, would the enzyme still be able to form hydrogen bonds with the substrate ?
Which substrate (the left or right one) do you think is more stable in the active site? Why? How?
Figure 3: This is an enzyme active site. Only the amino acids in the active site are drawn. The substrate is sitting directly in the center. Source: Created by Marc T. Facciotti (original work)
Prepare for the test: First, identify the type of macromolecule in the figure above. Second, draw in and label the appropriate interactions between the R groups and the substrate. Explain how these interactions might change if the pH of the solution changed.
Structural Instability of Enzymes
The fact that active sites are so well-suited to provide specific environmental conditions also means that they are subject to influences by the local environment. It is true that increasing the environmental temperature generally increases reaction rates, enzyme-catalyzed or otherwise. However, increasing or decreasing the temperature outside of an optimal range can affect chemical bonds within the active site in such a way that they are less well suited to bind substrates. High temperatures will eventually cause enzymes, like other biological molecules, to denature, a process that changes the natural properties of a substance. Likewise, the pH of the local environment can also affect enzyme function. Active site amino acid residues have their own acidic or basic properties that are optimal for catalysis. These residues are sensitive to changes in pH that can impair the way substrate molecules bind. Enzymes are suited to function best within a certain pH range, and, as with temperature, extreme pH values (acidic or basic) of the environment can cause enzymes to denature.
Figure 4: Enzymes have an optimal pH. The pH at which the enzyme is most active will be the pH where the active site R groups are protonated/deprotonated such that the substrate can enter the active site and the initial step in the reaction can begin. Some enzymes require a very low pH (acidic) to be completely active. In the human body, these enzymes are most likely located in the lower stomach, or located in lysosomes (a cellular organelle used to digest large compounds inside the cell). Source: http://biowiki.ucdavis.edu/Biochemis..._pH_Inhibition
The process where enzymes denature usually starts with the unwinding of the tertiary structure through destabilization of the bonds holding the tertiary structure together. Hydrogen bonds, ionic bonds and covalent bonds (disulfide bridges and peptide bonds) can all be disrupted by large changes in temperate and pH. Using the chart of enzyme activity and temperature below, make an energy story for the red enzyme. Explain what might be happening from temperature 37C to 95C.
Figure 5: Enzymes have an optimal temperature. The temperature at which the enzyme is most active will usually be the temperature where the structure of the enzyme is stable or uncompromised. Some enzymes require a specific temperature to remain active and not denature. Source: http://academic.brooklyn.cuny.edu/bi...ge/enz_act.htm
Induced Fit and Enzyme Function
For many years, scientists thought that enzyme-substrate binding took place in a simple “lock-and-key” fashion. This model asserted that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view called induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild shift in the enzyme’s structure that confirms an more productive binding arrangement between the enzyme and the transition state of the substrate. This energetically favorable binding maximizes the enzyme’s ability to catalyze its reaction.
When an enzyme binds its substrate, an enzyme-substrate complex is formed. This complex lowers the activation energy of the reaction and promotes its rapid progression in one of many ways. On a basic level, enzymes promote chemical reactions that involve more than one substrate by bringing the substrates together in an optimal orientation. The appropriate region (atoms and bonds) of one molecule is juxtaposed to the appropriate region of the other molecule with which it must react. Another way in which enzymes promote the reaction of their substrates is by creating an energetically favorable environment within the active site for the reaction to occur. Certain chemical reactions might proceed best in a slightly acidic or non-polar environment. The chemical properties that emerge from the particular arrangement of amino acid residues within an active site create the energetically favorable environment for an enzyme’s specific substrates to react.
The activation energy required for many reactions includes the energy involved in slightly contorting chemical bonds so that they can more easily react. Enzymatic action can aid this process. The enzyme-substrate complex can lower the activation energy by contorting substrate molecules in such a way as to facilitate bond-breaking. Finally, enzymes can also lower activation energies by taking part in the chemical reaction itself. The amino acid residues can provide certain ions or chemical groups that actually form covalent bonds with substrate molecules as a necessary step of the reaction process. In these cases, it is important to remember that the enzyme will always return to its original state at the completion of the reaction. One of the hallmark properties of enzymes is that they remain ultimately unchanged by the reactions they catalyze. After an enzyme is done catalyzing a reaction, it releases its product(s).
Figure 6: According to the induced-fit model, both enzyme and substrate undergo dynamic conformational changes upon binding. The enzyme contorts the substrate into its transition state, thereby increasing the rate of the reaction.
Creating an Energy story for the reaction above
Using the figure above, answer the questions posed in the energy story.
1. What are the reactants? What are the products?
2. What work was accomplished by the enzyme?
3. What state is the energy in initially? What state is the energy transformed into in the final state? This one might be tricky still, but try to identify where the energy is in the initial state and the final state.
Why regulate enzymes?
Cellular needs and conditions vary from cell to cell, and change within individual cells over time. The required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the needed amounts and functionality of different enzymes.
Regulation of Enzymes by Molecules
Enzymes can be regulated in ways that either promote or reduce their activity. There are many different kinds of molecules that inhibit or promote enzyme function, and various mechanisms exist for doing so. In some cases of enzyme inhibition, for example, an inhibitor molecule is similar enough to a substrate that it can bind to the active site and simply block the substrate from binding. When this happens, the enzyme is inhibited through competitive inhibition, because an inhibitor molecule competes with the substrate for active site binding. On the other hand, in noncompetitive inhibition, an inhibitor molecule binds to the enzyme in a location other than an allosteric site and still manages to block substrate binding to the active site.
Figure 7: Competitive and noncompetitive inhibition affect the rate of reaction differently. Competitive inhibitors affect the initial rate but do not affect the maximal rate, whereas noncompetitive inhibitors affect the maximal rate.
Some inhibitor molecules bind to enzymes in a location where their binding induces a conformational change that reduces the affinity of the enzyme for its substrate. This type of inhibition is called allosteric inhibition. Most allosterically regulated enzymes are made up of more than one polypeptide, meaning that they have more than one protein subunit. When an allosteric inhibitor binds to an enzyme, all active sites on the protein subunits are changed slightly such that they bind their substrates with less efficiency. There are allosteric activators as well as inhibitors. Allosteric activators bind to locations on an enzyme away from the active site, inducing a conformational change that increases the affinity of the enzyme’s active site(s) for its substrate(s).
Figure 8: Allosteric inhibitors modify the active site of the enzyme so that substrate binding is reduced or prevented. In contrast, allosteric activators modify the active site of the enzyme so that the affinity for the substrate increases.
Check out this short (1 minute) video on competitive vs. noncompetitive enzymatic inhibition. Also, take a look at this video (1.2 minutes) on feed back inhibition.
Many enzymes don’t work optimally, or even at all, unless bound to other specific non-protein helper molecules, either temporarily through ionic or hydrogen bonds or permanently through stronger covalent bonds. Two types of helper molecules are cofactors and coenzymes. Binding to these molecules promotes optimal conformation and function for their respective enzymes. Cofactors are inorganic ions such as iron (Fe2+) and magnesium (Mg2+). One example of an enzyme that requires a metal ion as a cofactor is the enzyme that builds DNA molecules, DNA polymerase, which requires bound zinc ion (Zn2+) to function. Coenzymes are organic helper molecules, with a basic atomic structure made up of carbon and hydrogen, which are required for enzyme action. The most common sources of coenzymes are dietary vitamins. Some vitamins are precursors to coenzymes and others act directly as coenzymes. Vitamin C is a coenzyme for multiple enzymes that take part in building the important connective tissue component, collagen. An important step in the breakdown of glucose to yield energy is catalysis by a multi-enzyme complex called pyruvate dehydrogenase. Pyruvate dehydrogenase is a complex of several enzymes that actually requires one cofactor (a magnesium ion) and five different organic coenzymes to catalyze its specific chemical reaction. Therefore, enzyme function is, in part, regulated by an abundance of various cofactors and coenzymes, which are supplied primarily by the diets of most organisms.
In eukaryotic cells, molecules such as enzymes are usually compartmentalized into different organelles. This allows for yet another level of regulation of enzyme activity. Enzymes required only for certain cellular processes can be housed separately along with their substrates, allowing for more efficient chemical reactions. Examples of this sort of enzyme regulation based on location and proximity include the enzymes involved in the latter stages of cellular respiration, which take place exclusively in the mitochondria, and the enzymes involved in the digestion of cellular debris and foreign materials, located within lysosomes.
The following links will take you to a series of videos on kinetics. The first link contains 4 videos on reaction rates and the second link contains 9 videos related to the relationship between reaction rates and concentration. These videos are supplemental and are provided to give you an outside resource to further explore enzyme kinetics.
Introduction to enzyme kinetics
Enzyme Active Site and Substrate Specificity
The chemical reactants to which an enzyme binds are the enzyme’s substrates. There may be one or more substrates, depending on the particular chemical reaction. In some reactions, a single-reactant substrate is broken down into multiple products. In others, two substrates may come together to create one larger molecule. Two reactants might also enter a reaction, both become modified, and leave the reaction as two products. The location within the enzyme where the substrate binds is called the enzyme’s active site. The active site is where the “action” happens, so to speak. Since enzymes are proteins, there is a unique combination of amino acid residues (also called side chains, or R groups) within the active site. Each residue is characterized by different properties. Residues can be large or small, weakly acidic or basic, hydrophilic or hydrophobic, positively or negatively charged, or neutral. The unique combination of amino acid residues, their positions, sequences, structures, and properties, creates a very specific chemical environment within the active site. This specific environment is suited to bind, albeit briefly, to a specific chemical substrate (or substrates). Due to this jigsaw puzzle-like match between an enzyme and its substrates (which adapts to find the best fit between the transition state and the active site), enzymes are known for their specificity. The “best fit” results from the shape and the amino acid functional group’s attraction to the substrate. There is a specifically matched enzyme for each substrate and, thus, for each chemical reaction however, there is flexibility as well.
The fact that active sites are so perfectly suited to provide specific environmental conditions also means that they are subject to influences by the local environment. It is true that increasing the environmental temperature generally increases reaction rates, enzyme-catalyzed or otherwise. However, increasing or decreasing the temperature outside of an optimal range can affect chemical bonds within the active site in such a way that they are less well suited to bind substrates. High temperatures will eventually cause enzymes, like other biological molecules, to denature, a process that changes the natural properties of a substance. Likewise, the pH of the local environment can also affect enzyme function. Active site amino acid residues have their own acidic or basic properties that are optimal for catalysis. These residues are sensitive to changes in pH that can impair the way substrate molecules bind. Enzymes are suited to function best within a certain pH range, and, as with temperature, extreme pH values (acidic or basic) of the environment can cause enzymes to denature.
Hydrogen peroxide is a toxic product of many chemical reactions that occur in living things. Although it is produced in small amounts, living things must detoxify this compound and break down hydrogen peroxide into water and oxygen, two non-harmful molecules. The organelle responsible for destroying hydrogen peroxide is the peroxisome using the enzyme catalase. Both plants and animals have peroxisomes with catalase. The catalase sample for today’s lab will be from a potato.
What are microbes?
Microbes are living, single-celled organisms such as fungi and bacteria. Microbes are the most effective producers of enzymes. These naturally-occuring enzyme factories are at the heart of our business, and can be used in a variety of agricultural and industrial processes.
Microbes give farmers a new biological toolkit to increase yields and protect crops. They can also improve livestock health, growth and feed utilization. Our customers in wastewater treatment and biogas use them to improve efficiency and as processing aids.
Protein Activity and Cellular Metabolism
Proteins have a crucial role in various biological activities. Get to know how proteins are able to perform as enzymes, cofactors, or regulators. In this tutorial, you will also know the common metabolic pathways of biomolecules, such as glucose and other carbohydrates, fats, proteins and amino acids, and essential nutrients.
Plants are responsible for incredible feats of molecular transformation. Plant processes, such as photosynthesis, photophosphorylation, chemiosmosis, carbon fixing reactions, respiration, are presented in this tutorial.
Genetic Information and Protein Synthesis
Genes are expressed through the process of protein synthesis. This elaborate tutorial provides an in-depth review of the different steps of the biological production of protein starting from the gene up to the process of secretion. Also included are topics on DNA replication during interphase of the cell cycle, DNA mutation and repair mechanisms, gene pool, modification, and diseases.
Gene Action – Operon Hypothesis
Learn how the way genes control and determine every aspect of the body. This lesson uses lac operon as an example. ..
Plant Cell Defense
Plants protect themselves by releasing hydrogen peroxide to fight against fungal invasion. Another way is by secreting compounds, such as lignin, ethylene, galls, and tannins. Find out how these mechanisms protect the plants from pathogens.
Digestion and Absorption of Food
The gastrointestinal system breaks down particles of ingested food into molecular forms by enzymes through digestion and then transferred to the internal environment by absorption. Find out more about these processes carried out by the gastrointestinal system through this tutorial.
By the late 17th and early 18th centuries, the digestion of meat by stomach secretions  and the conversion of starch to sugars by plant extracts and saliva were known but the mechanisms by which these occurred had not been identified. 
French chemist Anselme Payen was the first to discover an enzyme, diastase, in 1833.  A few decades later, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur concluded that this fermentation was caused by a vital force contained within the yeast cells called "ferments", which were thought to function only within living organisms. He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells." 
In 1877, German physiologist Wilhelm Kühne (1837–1900) first used the term enzyme, which comes from Greek ἔνζυμον, "leavened" or "in yeast", to describe this process.  The word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. 
Eduard Buchner submitted his first paper on the study of yeast extracts in 1897. In a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture.  He named the enzyme that brought about the fermentation of sucrose "zymase".  In 1907, he received the Nobel Prize in Chemistry for "his discovery of cell-free fermentation". Following Buchner's example, enzymes are usually named according to the reaction they carry out: the suffix -ase is combined with the name of the substrate (e.g., lactase is the enzyme that cleaves lactose) or to the type of reaction (e.g., DNA polymerase forms DNA polymers). 
The biochemical identity of enzymes was still unknown in the early 1900s. Many scientists observed that enzymatic activity was associated with proteins, but others (such as Nobel laureate Richard Willstätter) argued that proteins were merely carriers for the true enzymes and that proteins per se were incapable of catalysis.  In 1926, James B. Sumner showed that the enzyme urease was a pure protein and crystallized it he did likewise for the enzyme catalase in 1937. The conclusion that pure proteins can be enzymes was definitively demonstrated by John Howard Northrop and Wendell Meredith Stanley, who worked on the digestive enzymes pepsin (1930), trypsin and chymotrypsin. These three scientists were awarded the 1946 Nobel Prize in Chemistry. 
The discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This was first done for lysozyme, an enzyme found in tears, saliva and egg whites that digests the coating of some bacteria the structure was solved by a group led by David Chilton Phillips and published in 1965.  This high-resolution structure of lysozyme marked the beginning of the field of structural biology and the effort to understand how enzymes work at an atomic level of detail. 
Enzymes can be classified by two main criteria: either amino acid sequence similarity (and thus evolutionary relationship) or enzymatic activity.
Enzyme activity. An enzyme's name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase.  : 8.1.3 Examples are lactase, alcohol dehydrogenase and DNA polymerase. Different enzymes that catalyze the same chemical reaction are called isozymes.  : 10.3
The International Union of Biochemistry and Molecular Biology have developed a nomenclature for enzymes, the EC numbers (for "Enzyme Commission"). Each enzyme is described by "EC" followed by a sequence of four numbers which represent the hierarchy of enzymatic activity (from very general to very specific). That is, the first number broadly classifies the enzyme based on its mechanism while the other digits add more and more specificity. 
The top-level classification is:
- EC 1, Oxidoreductases: catalyze oxidation/reduction reactions
- EC 2, Transferases: transfer a functional group (e.g. a methyl or phosphate group)
- EC 3, Hydrolases: catalyze the hydrolysis of various bonds
- EC 4, Lyases: cleave various bonds by means other than hydrolysis and oxidation
- EC 5, Isomerases: catalyze isomerization changes within a single molecule
- EC 6, Ligases: join two molecules with covalent bonds.
These sections are subdivided by other features such as the substrate, products, and chemical mechanism. An enzyme is fully specified by four numerical designations. For example, hexokinase (EC 184.108.40.206) is a transferase (EC 2) that adds a phosphate group (EC 2.7) to a hexose sugar, a molecule containing an alcohol group (EC 2.7.1). 
Sequence similarity. EC categories do not reflect sequence similarity. For instance, two ligases of the same EC number that catalyze exactly the same reaction can have completely different sequences. Independent of their function, enzymes, like any other proteins, have been classified by their sequence similarity into numerous families. These families have been documented in dozens of different protein and protein family databases such as Pfam. 
Enzymes are generally globular proteins, acting alone or in larger complexes. The sequence of the amino acids specifies the structure which in turn determines the catalytic activity of the enzyme.  Although structure determines function, a novel enzymatic activity cannot yet be predicted from structure alone.  Enzyme structures unfold (denature) when heated or exposed to chemical denaturants and this disruption to the structure typically causes a loss of activity.  Enzyme denaturation is normally linked to temperatures above a species' normal level as a result, enzymes from bacteria living in volcanic environments such as hot springs are prized by industrial users for their ability to function at high temperatures, allowing enzyme-catalysed reactions to be operated at a very high rate.
Enzymes are usually much larger than their substrates. Sizes range from just 62 amino acid residues, for the monomer of 4-oxalocrotonate tautomerase,  to over 2,500 residues in the animal fatty acid synthase.  Only a small portion of their structure (around 2–4 amino acids) is directly involved in catalysis: the catalytic site.  This catalytic site is located next to one or more binding sites where residues orient the substrates. The catalytic site and binding site together compose the enzyme's active site. The remaining majority of the enzyme structure serves to maintain the precise orientation and dynamics of the active site. 
In some enzymes, no amino acids are directly involved in catalysis instead, the enzyme contains sites to bind and orient catalytic cofactors.  Enzyme structures may also contain allosteric sites where the binding of a small molecule causes a conformational change that increases or decreases activity. 
A small number of RNA-based biological catalysts called ribozymes exist, which again can act alone or in complex with proteins. The most common of these is the ribosome which is a complex of protein and catalytic RNA components.  : 2.2
Enzymes must bind their substrates before they can catalyse any chemical reaction. Enzymes are usually very specific as to what substrates they bind and then the chemical reaction catalysed. Specificity is achieved by binding pockets with complementary shape, charge and hydrophilic/hydrophobic characteristics to the substrates. Enzymes can therefore distinguish between very similar substrate molecules to be chemoselective, regioselective and stereospecific. 
Some of the enzymes showing the highest specificity and accuracy are involved in the copying and expression of the genome. Some of these enzymes have "proof-reading" mechanisms. Here, an enzyme such as DNA polymerase catalyzes a reaction in a first step and then checks that the product is correct in a second step.  This two-step process results in average error rates of less than 1 error in 100 million reactions in high-fidelity mammalian polymerases.  : 5.3.1 Similar proofreading mechanisms are also found in RNA polymerase,  aminoacyl tRNA synthetases  and ribosomes. 
Conversely, some enzymes display enzyme promiscuity, having broad specificity and acting on a range of different physiologically relevant substrates. Many enzymes possess small side activities which arose fortuitously (i.e. neutrally), which may be the starting point for the evolutionary selection of a new function.  
"Lock and key" model
To explain the observed specificity of enzymes, in 1894 Emil Fischer proposed that both the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another.  This is often referred to as "the lock and key" model.  : 8.3.2 This early model explains enzyme specificity, but fails to explain the stabilization of the transition state that enzymes achieve. 
Induced fit model
In 1958, Daniel Koshland suggested a modification to the lock and key model: since enzymes are rather flexible structures, the active site is continuously reshaped by interactions with the substrate as the substrate interacts with the enzyme.  As a result, the substrate does not simply bind to a rigid active site the amino acid side-chains that make up the active site are molded into the precise positions that enable the enzyme to perform its catalytic function. In some cases, such as glycosidases, the substrate molecule also changes shape slightly as it enters the active site.  The active site continues to change until the substrate is completely bound, at which point the final shape and charge distribution is determined.  Induced fit may enhance the fidelity of molecular recognition in the presence of competition and noise via the conformational proofreading mechanism. 
Enzymes can accelerate reactions in several ways, all of which lower the activation energy (ΔG ‡ , Gibbs free energy) 
- By stabilizing the transition state:
- Creating an environment with a charge distribution complementary to that of the transition state to lower its energy 
- By providing an alternative reaction pathway:
- Temporarily reacting with the substrate, forming a covalent intermediate to provide a lower energy transition state 
- By destabilising the substrate ground state:
- Distorting bound substrate(s) into their transition state form to reduce the energy required to reach the transition state 
- By orienting the substrates into a productive arrangement to reduce the reaction entropy change  (the contribution of this mechanism to catalysis is relatively small) 
Enzymes may use several of these mechanisms simultaneously. For example, proteases such as trypsin perform covalent catalysis using a catalytic triad, stabilise charge build-up on the transition states using an oxyanion hole, complete hydrolysis using an oriented water substrate. 
Enzymes are not rigid, static structures instead they have complex internal dynamic motions – that is, movements of parts of the enzyme's structure such as individual amino acid residues, groups of residues forming a protein loop or unit of secondary structure, or even an entire protein domain. These motions give rise to a conformational ensemble of slightly different structures that interconvert with one another at equilibrium. Different states within this ensemble may be associated with different aspects of an enzyme's function. For example, different conformations of the enzyme dihydrofolate reductase are associated with the substrate binding, catalysis, cofactor release, and product release steps of the catalytic cycle,  consistent with catalytic resonance theory.
Substrate presentation is a process where the enzyme is sequestered away from its substrate. Enzymes can be sequestered to the plasma membrane away from a substrate in the nucleus or cytosol. Or within the membrane, an enzyme can be sequestered into lipid rafts away from its substrate in the disordered region. When the enzyme is released it mixes with its substrate. Alternatively, the enzyme can be sequestered near its substrate to activate the enzyme. For example, the enzyme can be soluble and upon activation bind to a lipid in the plasma membrane and then act upon molecules in the plasma membrane.
Allosteric sites are pockets on the enzyme, distinct from the active site, that bind to molecules in the cellular environment. These molecules then cause a change in the conformation or dynamics of the enzyme that is transduced to the active site and thus affects the reaction rate of the enzyme.  In this way, allosteric interactions can either inhibit or activate enzymes. Allosteric interactions with metabolites upstream or downstream in an enzyme's metabolic pathway cause feedback regulation, altering the activity of the enzyme according to the flux through the rest of the pathway. 
Some enzymes do not need additional components to show full activity. Others require non-protein molecules called cofactors to be bound for activity.  Cofactors can be either inorganic (e.g., metal ions and iron-sulfur clusters) or organic compounds (e.g., flavin and heme). These cofactors serve many purposes for instance, metal ions can help in stabilizing nucleophilic species within the active site.  Organic cofactors can be either coenzymes, which are released from the enzyme's active site during the reaction, or prosthetic groups, which are tightly bound to an enzyme. Organic prosthetic groups can be covalently bound (e.g., biotin in enzymes such as pyruvate carboxylase). 
An example of an enzyme that contains a cofactor is carbonic anhydrase, which uses a zinc cofactor bound as part of its active site.  These tightly bound ions or molecules are usually found in the active site and are involved in catalysis.  : 8.1.1 For example, flavin and heme cofactors are often involved in redox reactions.  : 17
Enzymes that require a cofactor but do not have one bound are called apoenzymes or apoproteins. An enzyme together with the cofactor(s) required for activity is called a holoenzyme (or haloenzyme). The term holoenzyme can also be applied to enzymes that contain multiple protein subunits, such as the DNA polymerases here the holoenzyme is the complete complex containing all the subunits needed for activity.  : 8.1.1
Coenzymes are small organic molecules that can be loosely or tightly bound to an enzyme. Coenzymes transport chemical groups from one enzyme to another.  Examples include NADH, NADPH and adenosine triphosphate (ATP). Some coenzymes, such as flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), thiamine pyrophosphate (TPP), and tetrahydrofolate (THF), are derived from vitamins. These coenzymes cannot be synthesized by the body de novo and closely related compounds (vitamins) must be acquired from the diet. The chemical groups carried include:
- the hydride ion (H − ), carried by NAD or NADP +
- the phosphate group, carried by adenosine triphosphate
- the acetyl group, carried by coenzyme A
- formyl, methenyl or methyl groups, carried by folic acid and
- the methyl group, carried by S-adenosylmethionine
Since coenzymes are chemically changed as a consequence of enzyme action, it is useful to consider coenzymes to be a special class of substrates, or second substrates, which are common to many different enzymes. For example, about 1000 enzymes are known to use the coenzyme NADH. 
Coenzymes are usually continuously regenerated and their concentrations maintained at a steady level inside the cell. For example, NADPH is regenerated through the pentose phosphate pathway and S-adenosylmethionine by methionine adenosyltransferase. This continuous regeneration means that small amounts of coenzymes can be used very intensively. For example, the human body turns over its own weight in ATP each day. 
As with all catalysts, enzymes do not alter the position of the chemical equilibrium of the reaction. In the presence of an enzyme, the reaction runs in the same direction as it would without the enzyme, just more quickly.  : 8.2.3 For example, carbonic anhydrase catalyzes its reaction in either direction depending on the concentration of its reactants: 
The rate of a reaction is dependent on the activation energy needed to form the transition state which then decays into products. Enzymes increase reaction rates by lowering the energy of the transition state. First, binding forms a low energy enzyme-substrate complex (ES). Second, the enzyme stabilises the transition state such that it requires less energy to achieve compared to the uncatalyzed reaction (ES ‡ ). Finally the enzyme-product complex (EP) dissociates to release the products.  : 8.3
Enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive" a thermodynamically unfavourable one so that the combined energy of the products is lower than the substrates. For example, the hydrolysis of ATP is often used to drive other chemical reactions. 
Enzyme kinetics is the investigation of how enzymes bind substrates and turn them into products.  The rate data used in kinetic analyses are commonly obtained from enzyme assays. In 1913 Leonor Michaelis and Maud Leonora Menten proposed a quantitative theory of enzyme kinetics, which is referred to as Michaelis–Menten kinetics.  The major contribution of Michaelis and Menten was to think of enzyme reactions in two stages. In the first, the substrate binds reversibly to the enzyme, forming the enzyme-substrate complex. This is sometimes called the Michaelis–Menten complex in their honor. The enzyme then catalyzes the chemical step in the reaction and releases the product. This work was further developed by G. E. Briggs and J. B. S. Haldane, who derived kinetic equations that are still widely used today. 
Enzyme rates depend on solution conditions and substrate concentration. To find the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is seen. This is shown in the saturation curve on the right. Saturation happens because, as substrate concentration increases, more and more of the free enzyme is converted into the substrate-bound ES complex. At the maximum reaction rate (Vmax) of the enzyme, all the enzyme active sites are bound to substrate, and the amount of ES complex is the same as the total amount of enzyme.  : 8.4
Vmax is only one of several important kinetic parameters. The amount of substrate needed to achieve a given rate of reaction is also important. This is given by the Michaelis–Menten constant (Km), which is the substrate concentration required for an enzyme to reach one-half its maximum reaction rate generally, each enzyme has a characteristic KM for a given substrate. Another useful constant is kcat, also called the turnover number, which is the number of substrate molecules handled by one active site per second.  : 8.4
The efficiency of an enzyme can be expressed in terms of kcat/Km. This is also called the specificity constant and incorporates the rate constants for all steps in the reaction up to and including the first irreversible step. Because the specificity constant reflects both affinity and catalytic ability, it is useful for comparing different enzymes against each other, or the same enzyme with different substrates. The theoretical maximum for the specificity constant is called the diffusion limit and is about 10 8 to 10 9 (M −1 s −1 ). At this point every collision of the enzyme with its substrate will result in catalysis, and the rate of product formation is not limited by the reaction rate but by the diffusion rate. Enzymes with this property are called catalytically perfect or kinetically perfect. Example of such enzymes are triose-phosphate isomerase, carbonic anhydrase, acetylcholinesterase, catalase, fumarase, β-lactamase, and superoxide dismutase.  : 8.4.2 The turnover of such enzymes can reach several million reactions per second.  : 9.2 But most enzymes are far from perfect: the average values of k c a t / K m Michaelis–Menten kinetics relies on the law of mass action, which is derived from the assumptions of free diffusion and thermodynamically driven random collision. Many biochemical or cellular processes deviate significantly from these conditions, because of macromolecular crowding and constrained molecular movement.  More recent, complex extensions of the model attempt to correct for these effects.  Enzyme reaction rates can be decreased by various types of enzyme inhibitors.  : 73–74 A competitive inhibitor and substrate cannot bind to the enzyme at the same time.  Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example, the drug methotrexate is a competitive inhibitor of the enzyme dihydrofolate reductase, which catalyzes the reduction of dihydrofolate to tetrahydrofolate.  The similarity between the structures of dihydrofolate and this drug are shown in the accompanying figure. This type of inhibition can be overcome with high substrate concentration. In some cases, the inhibitor can bind to a site other than the binding-site of the usual substrate and exert an allosteric effect to change the shape of the usual binding-site.  A non-competitive inhibitor binds to a site other than where the substrate binds. The substrate still binds with its usual affinity and hence Km remains the same. However the inhibitor reduces the catalytic efficiency of the enzyme so that Vmax is reduced. In contrast to competitive inhibition, non-competitive inhibition cannot be overcome with high substrate concentration.  : 76–78 An uncompetitive inhibitor cannot bind to the free enzyme, only to the enzyme-substrate complex hence, these types of inhibitors are most effective at high substrate concentration. In the presence of the inhibitor, the enzyme-substrate complex is inactive.  : 78 This type of inhibition is rare.  A mixed inhibitor binds to an allosteric site and the binding of the substrate and the inhibitor affect each other. The enzyme's function is reduced but not eliminated when bound to the inhibitor. This type of inhibitor does not follow the Michaelis–Menten equation.  : 76–78 An irreversible inhibitor permanently inactivates the enzyme, usually by forming a covalent bond to the protein.  Penicillin  and aspirin  are common drugs that act in this manner. In many organisms, inhibitors may act as part of a feedback mechanism. If an enzyme produces too much of one substance in the organism, that substance may act as an inhibitor for the enzyme at the beginning of the pathway that produces it, causing production of the substance to slow down or stop when there is sufficient amount. This is a form of negative feedback. Major metabolic pathways such as the citric acid cycle make use of this mechanism.  : 17.2.2 Since inhibitors modulate the function of enzymes they are often used as drugs. Many such drugs are reversible competitive inhibitors that resemble the enzyme's native substrate, similar to methotrexate above other well-known examples include statins used to treat high cholesterol,  and protease inhibitors used to treat retroviral infections such as HIV.  A common example of an irreversible inhibitor that is used as a drug is aspirin, which inhibits the COX-1 and COX-2 enzymes that produce the inflammation messenger prostaglandin.  Other enzyme inhibitors are poisons. For example, the poison cyanide is an irreversible enzyme inhibitor that combines with the copper and iron in the active site of the enzyme cytochrome c oxidase and blocks cellular respiration.  As enzymes are made up of proteins, their actions are sensitive to change in many physio chemical factors such as pH, temperature, substrate concentration, etc. The following table shows pH optima for various enzymes. 
Types of inhibition
Functions of inhibitors
Enzyme Optimum pH pH description Pepsin 1.5–1.6 Highly acidic Invertase 4.5 Acidic Lipase (stomach) 4.0–5.0 Acidic Lipase (castor oil) 4.7 Acidic Lipase (pancreas) 8.0 Alkaline Amylase (malt) 4.6–5.2 Acidic Amylase (pancreas) 6.7–7.0 Acidic-neutral Cellobiase 5.0 Acidic Maltase 6.1–6.8 Acidic Sucrase 6.2 Acidic Catalase 7.0 Neutral Urease 7.0 Neutral Cholinesterase 7.0 Neutral Ribonuclease 7.0–7.5 Neutral Fumarase 7.8 Alkaline Trypsin 7.8–8.7 Alkaline Adenosine triphosphate 9.0 Alkaline Arginase 10.0 Highly alkaline
Michaelis–Menten kinetics relies on the law of mass action, which is derived from the assumptions of free diffusion and thermodynamically driven random collision. Many biochemical or cellular processes deviate significantly from these conditions, because of macromolecular crowding and constrained molecular movement.  More recent, complex extensions of the model attempt to correct for these effects. 
Enzyme reaction rates can be decreased by various types of enzyme inhibitors.  : 73–74
A competitive inhibitor and substrate cannot bind to the enzyme at the same time.  Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example, the drug methotrexate is a competitive inhibitor of the enzyme dihydrofolate reductase, which catalyzes the reduction of dihydrofolate to tetrahydrofolate.  The similarity between the structures of dihydrofolate and this drug are shown in the accompanying figure. This type of inhibition can be overcome with high substrate concentration. In some cases, the inhibitor can bind to a site other than the binding-site of the usual substrate and exert an allosteric effect to change the shape of the usual binding-site. 
A non-competitive inhibitor binds to a site other than where the substrate binds. The substrate still binds with its usual affinity and hence Km remains the same. However the inhibitor reduces the catalytic efficiency of the enzyme so that Vmax is reduced. In contrast to competitive inhibition, non-competitive inhibition cannot be overcome with high substrate concentration.  : 76–78
An uncompetitive inhibitor cannot bind to the free enzyme, only to the enzyme-substrate complex hence, these types of inhibitors are most effective at high substrate concentration. In the presence of the inhibitor, the enzyme-substrate complex is inactive.  : 78 This type of inhibition is rare. 
A mixed inhibitor binds to an allosteric site and the binding of the substrate and the inhibitor affect each other. The enzyme's function is reduced but not eliminated when bound to the inhibitor. This type of inhibitor does not follow the Michaelis–Menten equation.  : 76–78
An irreversible inhibitor permanently inactivates the enzyme, usually by forming a covalent bond to the protein.  Penicillin  and aspirin  are common drugs that act in this manner.
In many organisms, inhibitors may act as part of a feedback mechanism. If an enzyme produces too much of one substance in the organism, that substance may act as an inhibitor for the enzyme at the beginning of the pathway that produces it, causing production of the substance to slow down or stop when there is sufficient amount. This is a form of negative feedback. Major metabolic pathways such as the citric acid cycle make use of this mechanism.  : 17.2.2
Since inhibitors modulate the function of enzymes they are often used as drugs. Many such drugs are reversible competitive inhibitors that resemble the enzyme's native substrate, similar to methotrexate above other well-known examples include statins used to treat high cholesterol,  and protease inhibitors used to treat retroviral infections such as HIV.  A common example of an irreversible inhibitor that is used as a drug is aspirin, which inhibits the COX-1 and COX-2 enzymes that produce the inflammation messenger prostaglandin.  Other enzyme inhibitors are poisons. For example, the poison cyanide is an irreversible enzyme inhibitor that combines with the copper and iron in the active site of the enzyme cytochrome c oxidase and blocks cellular respiration. 
As enzymes are made up of proteins, their actions are sensitive to change in many physio chemical factors such as pH, temperature, substrate concentration, etc.
The following table shows pH optima for various enzymes. 
Enzymes serve a wide variety of functions inside living organisms. They are indispensable for signal transduction and cell regulation, often via kinases and phosphatases.  They also generate movement, with myosin hydrolyzing ATP to generate muscle contraction, and also transport cargo around the cell as part of the cytoskeleton.  Other ATPases in the cell membrane are ion pumps involved in active transport. Enzymes are also involved in more exotic functions, such as luciferase generating light in fireflies.  Viruses can also contain enzymes for infecting cells, such as the HIV integrase and reverse transcriptase, or for viral release from cells, like the influenza virus neuraminidase. 
An important function of enzymes is in the digestive systems of animals. Enzymes such as amylases and proteases break down large molecules (starch or proteins, respectively) into smaller ones, so they can be absorbed by the intestines. Starch molecules, for example, are too large to be absorbed from the intestine, but enzymes hydrolyze the starch chains into smaller molecules such as maltose and eventually glucose, which can then be absorbed. Different enzymes digest different food substances. In ruminants, which have herbivorous diets, microorganisms in the gut produce another enzyme, cellulase, to break down the cellulose cell walls of plant fiber. 
Several enzymes can work together in a specific order, creating metabolic pathways.  : 30.1 In a metabolic pathway, one enzyme takes the product of another enzyme as a substrate. After the catalytic reaction, the product is then passed on to another enzyme. Sometimes more than one enzyme can catalyze the same reaction in parallel this can allow more complex regulation: with, for example, a low constant activity provided by one enzyme but an inducible high activity from a second enzyme. 
Enzymes determine what steps occur in these pathways. Without enzymes, metabolism would neither progress through the same steps and could not be regulated to serve the needs of the cell. Most central metabolic pathways are regulated at a few key steps, typically through enzymes whose activity involves the hydrolysis of ATP. Because this reaction releases so much energy, other reactions that are thermodynamically unfavorable can be coupled to ATP hydrolysis, driving the overall series of linked metabolic reactions.  : 30.1
Control of activity
There are five main ways that enzyme activity is controlled in the cell.  : 30.1.1
Enzymes can be either activated or inhibited by other molecules. For example, the end product(s) of a metabolic pathway are often inhibitors for one of the first enzymes of the pathway (usually the first irreversible step, called committed step), thus regulating the amount of end product made by the pathways. Such a regulatory mechanism is called a negative feedback mechanism, because the amount of the end product produced is regulated by its own concentration.  : 141–48 Negative feedback mechanism can effectively adjust the rate of synthesis of intermediate metabolites according to the demands of the cells. This helps with effective allocations of materials and energy economy, and it prevents the excess manufacture of end products. Like other homeostatic devices, the control of enzymatic action helps to maintain a stable internal environment in living organisms.  : 141
Examples of post-translational modification include phosphorylation, myristoylation and glycosylation.  : 149–69 For example, in the response to insulin, the phosphorylation of multiple enzymes, including glycogen synthase, helps control the synthesis or degradation of glycogen and allows the cell to respond to changes in blood sugar.  Another example of post-translational modification is the cleavage of the polypeptide chain. Chymotrypsin, a digestive protease, is produced in inactive form as chymotrypsinogen in the pancreas and transported in this form to the stomach where it is activated. This stops the enzyme from digesting the pancreas or other tissues before it enters the gut. This type of inactive precursor to an enzyme is known as a zymogen  : 149–53 or proenzyme.
Enzyme production (transcription and translation of enzyme genes) can be enhanced or diminished by a cell in response to changes in the cell's environment. This form of gene regulation is called enzyme induction. For example, bacteria may become resistant to antibiotics such as penicillin because enzymes called beta-lactamases are induced that hydrolyse the crucial beta-lactam ring within the penicillin molecule.  Another example comes from enzymes in the liver called cytochrome P450 oxidases, which are important in drug metabolism. Induction or inhibition of these enzymes can cause drug interactions.  Enzyme levels can also be regulated by changing the rate of enzyme degradation.  : 30.1.1 The opposite of enzyme induction is enzyme repression.
Enzymes can be compartmentalized, with different metabolic pathways occurring in different cellular compartments. For example, fatty acids are synthesized by one set of enzymes in the cytosol, endoplasmic reticulum and Golgi and used by a different set of enzymes as a source of energy in the mitochondrion, through β-oxidation.  In addition, trafficking of the enzyme to different compartments may change the degree of protonation (e.g., the neutral cytoplasm and the acidic lysosome) or oxidative state (e.g., oxidizing periplasm or reducing cytoplasm) which in turn affects enzyme activity.  In contrast to partitioning into membrane bound organelles, enzyme subcellular localisation may also be altered through polymerisation of enzymes into macromolecular cytoplasmic filaments.  
In multicellular eukaryotes, cells in different organs and tissues have different patterns of gene expression and therefore have different sets of enzymes (known as isozymes) available for metabolic reactions. This provides a mechanism for regulating the overall metabolism of the organism. For example, hexokinase, the first enzyme in the glycolysis pathway, has a specialized form called glucokinase expressed in the liver and pancreas that has a lower affinity for glucose yet is more sensitive to glucose concentration.  This enzyme is involved in sensing blood sugar and regulating insulin production. 
Involvement in disease
Since the tight control of enzyme activity is essential for homeostasis, any malfunction (mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to a genetic disease. The malfunction of just one type of enzyme out of the thousands of types present in the human body can be fatal. An example of a fatal genetic disease due to enzyme insufficiency is Tay–Sachs disease, in which patients lack the enzyme hexosaminidase.  
One example of enzyme deficiency is the most common type of phenylketonuria. Many different single amino acid mutations in the enzyme phenylalanine hydroxylase, which catalyzes the first step in the degradation of phenylalanine, result in build-up of phenylalanine and related products. Some mutations are in the active site, directly disrupting binding and catalysis, but many are far from the active site and reduce activity by destabilising the protein structure, or affecting correct oligomerisation.   This can lead to intellectual disability if the disease is untreated.  Another example is pseudocholinesterase deficiency, in which the body's ability to break down choline ester drugs is impaired.  Oral administration of enzymes can be used to treat some functional enzyme deficiencies, such as pancreatic insufficiency  and lactose intolerance. 
Another way enzyme malfunctions can cause disease comes from germline mutations in genes coding for DNA repair enzymes. Defects in these enzymes cause cancer because cells are less able to repair mutations in their genomes. This causes a slow accumulation of mutations and results in the development of cancers. An example of such a hereditary cancer syndrome is xeroderma pigmentosum, which causes the development of skin cancers in response to even minimal exposure to ultraviolet light.  
Similar to any other protein, enzymes change over time through mutations and sequence divergence. Given their central role in metabolism, enzyme evolution plays a critical role in adaptation. A key question is therefore whether and how enzymes can change their enzymatic activities alongside. It is generally accepted that many new enzyme activities have evolved through gene duplication and mutation of the duplicate copies although evolution can also happen without duplication. One example of an enzyme that has changed its activity is the ancestor of methionyl amino peptidase (MAP) and creatine amidinohydrolase (creatinase) which are clearly homologous but catalyze very different reactions (MAP removes the amino-terminal methionine in new proteins while creatinase hydrolyses creatine to sarcosine and urea). In addition, MAP is metal-ion dependent while creatinase is not, hence this property was also lost over time.  Small changes of enzymatic activity are extremely common among enzymes. In particular, substrate binding specificity (see above) can easily and quickly change with single amino acid changes in their substrate binding pockets. This is frequently seen in the main enzyme classes such as kinases. 
Artificial (in vitro) evolution is now commonly used to modify enzyme activity or specificity for industrial applications (see below).
Enzymes are used in the chemical industry and other industrial applications when extremely specific catalysts are required. Enzymes in general are limited in the number of reactions they have evolved to catalyze and also by their lack of stability in organic solvents and at high temperatures. As a consequence, protein engineering is an active area of research and involves attempts to create new enzymes with novel properties, either through rational design or in vitro evolution.   These efforts have begun to be successful, and a few enzymes have now been designed "from scratch" to catalyze reactions that do not occur in nature. 
How Enzymes Work
Most enzymes work by lowering the activation energy of a chemical reaction. Sometimes, their shape brings the reactants physically close together in the style, perhaps, of a sports-team coach or work-group manager intent on getting a task done more quickly. It is believed that when enzymes bind to a reactant, their shape changes in a way that destabilizes the reactant and makes it more susceptible to whatever chemical changes the reaction involves.
Reactions that can proceed without the input of energy are called exothermic reactions. In these reactions, the products, or the chemical(s) formed during the reaction, have a lower energy level than the chemicals that serve as the reaction's ingredients. In this way, molecules, like water, "seek" their own (energy) level atoms "prefer" to be in arrangements with lower total energy, just like water flows downhill to the lowest available physical point. Putting all of this together, it is clear that exothermic reactions always proceed naturally.
However, the fact that a reaction will occur even without input says nothing about the rate at which it will happen. If a substance taken into the body will naturally change into two derivative substances that can serve as direct sources of cellular energy, this does little good if the reaction naturally takes hours or days to complete. Also, even when the total energy of products is higher than that of the reactants, the energy path is not a smooth downhill slope on a graph instead, the products must attain a higher level of energy than that with which they began so that they can "get over the hump" and the reaction may proceed. This initial investment of energy into the reactants that pays off in the form of products is the aforementioned energy of activation, or Ea.
There are two types of inhibitors, competitive inhibitors and non-competitive inhibitors. If the inhibitor covalently binds to the enzyme, permanently altering the structure of the enzyme then it is referred to as being irreversible inhibition.
Competitive inhibitors work by having a similar shape to the usual substrate molecule and so they can bind to the active site of the enzyme, preventing the formation of enzyme-substrate complexes. These enzymes can be overcome by increasing the concentration of the substrate, as this increases the likelihood that a substrate molecule will interact with the active site instead of an inhibitor molecule.
Non-competitive inhibitors work by binding to an allosteric site on the enzyme. By binding to the allosteric site, it causes a conformational 3D change within the enzyme, changing the shape of the active site and thereby preventing it from binding to its substrate.
Typically, competitive inhibitors are reversible, while non-competitive inhibitors are irreversible.
Affect of Increasing Temperature
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