Looking for revision notes that are specific to the exam board you are studying? If so, click the links below to view our condensed, easy-to-understand revision notes for each exam board, practice exam question booklets, mindmap visual aids, interactive quizzes, PowerPoint presentations and a library of past papers directly from the exam boards. View AQA revision. View OCR revision. View Edexcel revision.

Author:Moogugami Kigalkree
Language:English (Spanish)
Published (Last):21 December 2012
PDF File Size:9.6 Mb
ePub File Size:16.85 Mb
Price:Free* [*Free Regsitration Required]

Several criteria must be met for a chemical reaction to happen. Obviously, the reactants must first find one another in space. Chemicals in solutions don't "plan" these collisions, they happen at random.

The rate frequency of collisions per second at which two reactants find one another will depend on their velocity determined by temperature and their concentration. In this Biology course, we'll assume temperature is a constant. Secondly, in addition to colliding, the molecules probably have to collide at the correct orientations, as not all collisions are potentially productive.

Thirdly, the molecules have to have sufficient energy to form the transition state. If the transition state is significantly above the average energy of the molecules which will be fairly uniform- a narrow distribution very very few of the molecules will have sufficient energy to form the unstable, high tension, distorted "transition state". Thus, even if the reactants collide frequently, and the reaction is energetically favorable, a reaction with a activation energy significantly above the average energy of the reactants is not going to progress on a timescale suitable for the life of a cell.

This is actually, and perhaps surprisingly, good news for the cell. It means that the cell can control metabolic flux by controlling the availability of catalysts. Although we and other biologists will often only consider one direction of a reaction, keep in mind that catalysts do not determine the direction of a reaction- they simply allow the reaction to occur in whichever direction is energetically favorable. They only reduce the activation energy required to reach the transition state. 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. Attribution: Marc T. Facciotti own work. Catalysts in biology are genetically encoded by the cell, and are called enzymes. Enzymes are made of protein s , often with non-protein cofactors that are intimately involved in the actual reaction catalyzed again, cofactors are part of the enzyme and are not "used up" in the reaction.

There are some interesting exceptions in which the catalysis is actually performed by an RNA molecule, the structure of which may be stabilized by small proteins. These genetically-encoded catalysts are called "ribozymes" will be discussed in more detail later in the course. Enzymes have an active site that provides a unique chemical environment, made up of certain amino acid R groups residues in a particular orientations and distance from one another.

This unique environment is well-suited to convert particular chemical reactants for that enzyme, called substrates, into unstable intermediates transition states.

Enzymes and substrates are thought to bind with an "induced fit", which means that enzymes and substrates undergo slight conformational adjustments upon substrate contact, leading to binding. This subtle change in enzyme shape allows the enzyme to rapidly bind potential substrates in an "open" conformation" and then generate a tighter "closed" catalytically active alternative conformation only when the correct substrate is correctly aligned in the active site.

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. Inhibition and activation of enzymes via other molecules are important ways that enzymes are regulated. Activators can also enhance the function of enzymes allosterically. 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.

Enzyme Active Site and Substrate Specificity. 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.

Since enzymes are proteins, there is a unique combination of amino acid R groups within the active site. Each amino acid side-chain is characterized by different properties.

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, enzymes can be extremely specific in their choice of substrates. This is an enzyme with two different substrates bound in the active site here conveniently squished down to 2 dimensions. The enzymes are represented as blobs, except for the active site which identifies three amino acids located in the active site and shows the R group for one of them.

The R group of R is interacting with the substrates through hydrogen bonding represented as dashed lines , as are some groups in the peptide backbone. Amino acid positions are denoted a single letter code for the amino acid followed immediately by "position of the amino acid vs. For example "R" means an R arginine is the th amino acid from the N terminus. Minor note- the R is this diagram is drawn incorrectly, though teh business end- where it connects to substrate- is OK.

At this point in the class you should be familiar with the chemical characteristics charge, polarity, hydrophobicity of the functional groups. For example, the R group of R in the enzyme depicted above is the amino acid Arginine arginine's single letter code happens to be R, which is a little confusing in this context and R's R group consists of several "amino" functional groups.

An amino functional group contains 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 partial positive charge, and the nitrogen atom will have a partial negative charge.

This allows amino groups to form hydrogen bonds with other polar compounds. Likewise, the backbone carbonyl oxygens of Valine V81 and Glycine G the backbone amino hydrogen of V81 are depicted engaged in hydrogen bonds with the small molecule substrate.

Look to see which atoms in the figure above are involved in the hydrogen bonds between the amino acid R groups and the substrate. Which substrate the left or right one do you think is more stable in the active site? This is a depiction of an enzyme active site. Only the amino acids in the active site are drawn; the numbers refer to their positions in the primary sequence of the protein and aren't really important here. The substrate is sitting directly in the center. Source: Created by Marc T.

Facciotti original work. First, identify the type of molecule in the center of the figure above. Second, draw in and label the appropriate interactions between the R groups and the substrate. 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 some 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, because the charges on the R groups, and therefore both ionic and H-bonding interactions can change with pH.

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. Enzymes have an optimal pH. Some enzymes require a very low pH acidic to be completely active.

In the human body, these enzymes are most likely located in the stomach, or located in lysosomes a cellular organelle used to digest large compounds inside the cell. The process where enzymes denature usually starts with the unwinding of the tertiary structure through destabilization of the bonds holding the tertiary structure together.

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. 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. 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. 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 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 all cases, it is important to remember that the enzyme will always return to its original state at the completion of the reaction. After an enzyme is done catalyzing a reaction, it releases its product s. Always keep in mind that enzymes can also facilitate the reverse reaction. 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.

Using the figure above, answer the questions posed in the energy story.


Allosteric enzyme

Allosteric control , in enzymology, inhibition or activation of an enzyme by a small regulatory molecule that interacts at a site allosteric site other than the active site at which catalytic activity occurs. The interaction changes the shape of the enzyme so as to affect the formation at the active site of the usual complex between the enzyme and its substrate the compound upon which it acts to form a product. As a result, the ability of the enzyme to catalyze a reaction is modified. This is the basis of the so-called induced-fit theory , which states that the binding of a substrate or some other molecule to an enzyme causes a change in the shape of the enzyme so as to enhance or inhibit its activity. The regulatory molecule may be a product of a synthetic pathway and inhibit an enzyme in that pathway see feedback inhibition , thereby preventing the further formation of itself. Other molecules act as activators; i. The enzyme adenyl cyclase , itself activated by the hormone adrenaline epinephrine , which is released when a mammal requires energy, catalyzes a reaction that results in the formation of the compound cyclic adenosine monophosphate cyclic AMP.


17: Enzymes and Allosteric Regulation

Several criteria must be met for a chemical reaction to happen. Obviously, the reactants must first find one another in space. Chemicals in solutions don't "plan" these collisions, they happen at random. The rate frequency of collisions per second at which two reactants find one another will depend on their velocity determined by temperature and their concentration. In this Biology course, we'll assume temperature is a constant. Secondly, in addition to colliding, the molecules probably have to collide at the correct orientations, as not all collisions are potentially productive. Thirdly, the molecules have to have sufficient energy to form the transition state.


Allosteric control

Allosteric enzymes are enzymes that change their conformational ensemble upon binding of an effector allosteric modulator which results in an apparent change in binding affinity at a different ligand binding site. This "action at a distance" through binding of one ligand affecting the binding of another at a distinctly different site, is the essence of the allosteric concept. Allostery plays a crucial role in many fundamental biological processes, including but not limited to cell signaling and the regulation of metabolism. Allosteric enzymes need not be oligomers as previously thought, [1] and in fact many systems have demonstrated allostery within single enzymes. The site to which the effector binds is termed the allosteric site. Allosteric sites allow effectors to bind to the protein, often resulting in a conformational change involving protein dynamics. Effectors that enhance the protein's activity are referred to as allosteric activators , whereas those that decrease the protein's activity are called allosteric inhibitors.


Structural Biochemistry/Enzyme/Allosteric Enzymes

Many enzymes do not demonstrate hyperbolic saturation kinetics, or typical Michaelis-Menten kinetics. Enzymes that display this non Michaelis-Menten behavior have common characteristics. A classic examples of allosterically regulated enzymes includes glycogen phosphorylase which breaks down intracellular glycogen reserves. Glycogen Phosphorylase. Another is aspartate transcarbamyolase, which catalyzes the first step in the synthesis of pyrimidine nucleotides.

Related Articles