Chemical Reactions and the enzimes LESSON N. 6 - PSYCHOBIOLOGY
Chemical reactions consist of interatomic interactions that take place at the level of their orbital, and therefore different from nuclear reactions (fusion and fission) which involve changes in the nucleus of the atoms. In the case of biological molecules, chemical reactions occur typically between atoms belonging to two different molecules, although in the case of the macromolecules is possible that chemical reactions take place within different molecules which form the macromolecule. Like all physical phenomena of our universe, even the biological chemical reactions must obey the principles of thermodynamics.
1) The total amount of energy of a system and an environment that surrounds it, remains constant consequently, whatever the transformations involving the system and the environment, there will never be neither destruction nor creation of energy. 2) All the energy transformations are ALWAYS accompanied by dissipation into the environment, in the form of heat, of a part of the free energy... i.e. energy usable to perform a job. This phenomenon is measured in accordance with the concept of entropy = disorder. This implies that any system and environment that surrounds him, will always increase the entropy and decrease the free energy. However, the living matter is able to control the flow and direction of free energy that is exchanged with the environment.
Constantly taking substances that provide energy: photosynthetic organisms chemosynthetic organisms heterotrophic organisms
Holding inside the body heat that should be dissipated to the outside: Plumage hair layer of fat
What are the chemical reactions specifically? They are atomic rearrangements consequent to impact between the molecules. In fact, an impact between two or more molecules, called reactants generates kinetic energy that can also be used as chemical energy adapted to break the bonds of the reactant molecules and forming new ones with different conformations giving rise to new molecules called products
Obviously not all the impacts of molecules give rise to chemical reactions. For this to happen it is necessary that the reactants collide with each other in an appropriate manner. Right relative positioning right speed If these parameters are correct, jointly provide the right activation energy
An important parameter of a chemical reaction is the speed with which it takes place. This is measured in amount of product molecules that are produced in each time unit. Eg. 0.05 mol / minute or 0.007 moles / second. The speed depends mainly on two parameters: Temperature: generally heat accelerates the probability that two molecules collides The higher concentration is the amount of molecules in a solvent the more is likely for them to meet Eg reptiles or fever
Another feature of a chemical reaction is the amount of free energy that it generates. It is measurable by comparing the energy content of the products with the energy content of the reactants. If the energy content of products < reactants, it is called exergonic or spontaneous reaction. Energy flows from the reactants to the environment. If the energy content of products > reactants, it is called endoergonic or induced reaction. Energy flows from the environment to the reactant.
Concrete example: Change of level of water masses. If we have to carry water from a lower to a higher level. It will serve energy which will be divided into two parts: The actually required energy to move water (buckets, Hydropump) Energy lost in the form of heat (heat that is generated in the human body to fatigue, or in the pump for friction of the gears) endoergonic reaction
Concrete example: Change of level of water masses. The falling water from a higher to a lower level is a spontaneous phenomenon that generates kinetic energy which in turn will be divided into two parts: A part which can be used for a job (a mill wheel) Energy lost as heat (heat generated on the rocks on the bottom of the waterfall) exergonic reaction
The activation threshold Although as mentioned, certain chemical reactions can be spontaneous, this occurs very rarely in biological organisms. Eg. The molecules of our body does not turn into CO2 and H2O despite this transformation from exergonic perspective is very favorable. This is because even the exergonic reactions need of an initial administration of energy, which will then be fully returned during the chemical reaction. Eg. Burn a sheet of paper
The direction of a chemical reaction What defines a molecule as a reactant or vice versa as a product is the direction within which the chemical reaction takes place. The energy that comes from colliding molecules, form an intermediate state called activated complex that has two possible ways of evolution To complete the reaction (more stable energy state) Revert to the initial condition (more stable energy state) Therefore, a chemical reaction is theoretically always reversible. And the direction in which it will proceed depends on many factors, the most important of which is the concentration of the reactants compared to the one of the products.
The direction of the chemical reaction
The chemical reaction in organic cells The probability of beginning and the speed of a chemical reaction, as previously mentioned, depend on the temperature and concentration. However, the cells do not have the possibility of easily and autonomously modify these parameters. For this reason, the evolution has equipped the organisms with catalyst which have the task of lowering the activation threshold of each reaction, in order to increase the numbers of reactants that have the energy content suitable to start the reaction. These substances: They bind in a highly specific way to the reactants of a given chemical reaction, lowering the activation threshold. Not becomes part of the reaction and does not determine the direction of development Are not "consumed" during the reaction, and then at the end they return again available for further reaction cycles.
Apart from the case of ribozymes (RNA molecules, involved in some of transcription and translation stages) the organic catalysts are always of proteins, called enzymes. Enzymes are proteins that specifically recognize certain molecules as reactants so as to give way to certain chemical reactions. Typically the name of the enzyme depends on the chemical reaction that will catalyze, defined by the ending -ase (eg. DNA-polymerase).
The ability of enzymes to catalyze chemical reactions in living matter, depends in large part from the fact that, being proteins, are characterized by a three-dimensional shape given to them by the tertiary structure (or quaternary). This structure allows the various regions of the enzyme to interact in a reversible or stable way with the reactants (substrate), with factors that regulate the enzymatic function or that redirect the intra-cellular localization. In particular, each enzyme has a site called active region that mediates the stereo-specific enzyme recognition, with the substrate. The enzyme and the substrate together, form the ES complex
A valid explanation model of interaction between enzyme and substrate was offered by Fisher in the early twentieth century, and has been defined key lock model. This model explains how the enzymes can have varying degrees of specificity for the substrate molecules. High specificity, host almost entirely the substrate molecules. This makes sure that only and only those molecules are able to bind to the enzyme, giving way to the chemical reaction. Low specificity, receives only a portion of the whole of the substrate molecule. This makes sure that different molecules, but with one part in common, can bind to the enzyme and start the chemical reaction.
The role of the enzyme-substrate complex is to lower the activation threshold of the reaction. This is because the enzyme still retains the reactants in a favorable position, in which most of the impact between their molecules, can start the reaction. In conclusion, the presence of an enzyme, allows the chemical reaction to take place at high speed by minimizing the energy required for its triggering.
However, as mentioned above, the enzyme may start the chemical reaction but it can not influence the direction. This means that the rule set previously about the concentration of reactants and products, remains valid and that the ES complex, as a result could have the formation of the products, but also the return to the individual reactants. To obviate this problem, the enzymes after the bond with the reactants, undergo a conformational change that can lead most likely to the formation of the products.
Sometimes the active site, as well as hosting the reactants, can also accommodate other molecules called enzyme inhibitors. These are very similar to those molecules that create the normal enzyme substrate, but they create a different complex called E-I. Unlike the reactants, the inhibitors are not processed into products by the chemical reaction. In some cases, the inhibitors are present in the cell and are used by the latter to adjust the enzymatic activity. More frequently these substances are introduced from outside the organism (drugs or poisonous substances).
Acetylsalicylic acid, artificial derivative of salicylic acid, present in the bark and leaves of the willow. It is an inhibitor of cyclooxygenase 1 and 2 enzymes that catalyze the prostaglandins that begin the inflammatory response. In particular aspirin decreases the production of prostaglandins in the hypothalamus which is the center that control the body temperature.
Enzyme inhibitors also can be classified into competitive and non-competitive inhibitors. On the basis of the stability of the complex E-I which they form. If the E-I complex is unstable, after a short time it will break again freeing the enzyme active site that could now accept a new molecule again. If the molecule is a reactant, the reaction will start, if it is another inhibitor, the enzyme is blocked once again temporarily. The probability of the new bond, as always depends on the concentration of the reactants or inhibitors (for this reason these are called competitive inhibitors). Because of their low toxicity competitive inhibitors are the active ingredient in many human drugs. If the E-I complex is stable. The enzyme is activated permanently and the only remedy that the cell has to activate new useful chemical reactions is to synthesize new enzymes. Due to the high toxicity, non-competitive inhibitors, they are common components of poisons released from animals or plants.
We have seen that the enzymes can be inactivated in a reversible or irreversible way. But these can also be activated, thus allowing the cell to regulate the functions. But what do they consist of precisely these adjustments? Typically they are almost all post-translation modifications. There are 6 types. They can act in a single, simultaneous or sequential way in each enzyme. Activation by proteolytic cuts Activation by a union with a cofactor Assembly with a sub-unit intracellular translocation Activation / Inactivation by changing electric charges allosteric regulation
1) Activation by proteolytic cuts 2) Activation by a union with a cofactor 3) Assembly with a sub-unit 4) intracellular translocation 5) Activation / Inactivation by changing electric charges 6) allosteric regulation The cell generates an inactive pro-enzyme, which will become active only as a result of the cutting of a part of its polypeptide chain. Many of the proteolytic enzyme catalysis of the digestive tract work that way.
1) Activation by proteolytic cuts 2) Activation by a union with a cofactor 3) Assembly with a sub-unit 4) intracellular translocation 5) Activation / Inactivation by changing electric charges 6) allosteric regulation In this case the enzyme not only activates after the union with the reactants, but it is necessary that it also binds a cofactor. For example in the neuron, the enzyme PKA (protein kinase A), involved in signal transduction processes, is activated by binding to the nucleotide camp (cyclic AMP)
1) Activation by proteolytic cuts 2) Activation by a union with a cofactor 3) Assembly with a sub-unit 4) intracellular translocation 5) Activation / Inactivation by changing electric charges 6) allosteric regulation Individual inactive sub-units, are joined together to form the complete enzyme that will become active. An example im the neurons is represented by the enzyme adenylate cyclase which produces the starting camp from ATP. By itself this enzyme is inactive, but when it is assembled a subunit alpha s, taken from the G protein that is next, then the enzyme is active.
1) Activation by proteolytic cuts 2) Activation by a union with a cofactor 3) Assembly with a sub-unit 4) intracellular translocation 5) Activation / Inactivation by changing electric charges 6) allosteric regulation The enzyme molecule is transported from an intracellular site in which it could not be active, to a second intracellular site in which it can exert its function Eg. Enzymes of oxidative phosphorylation begin to function after being transported into the mitochondria.
1) Activation by proteolytic cuts 2) Activation by a union with a cofactor 3) Assembly with a sub-unit 4) intracellular translocation 5) Activation / Inactivation by changing electric charges 6) allosteric regulation Functional groups with positive or negative charge are added or subtracted, eg the phosphate groups. Then we find again the phosphorylation and dephosphorylation processes that typically involve the amino acids serine, threonine or tyrosine. Eg. Protein kinase or phosphatase.
1) Activation by proteolytic cuts 2) Activation by a union with a cofactor 3) Assembly with a sub-unit 4) intracellular translocation 5) Activation / Inactivation by changing electric charges 6) allosteric regulation Relates to a particular type of enzymes (typically metabolic) that on their surface in addition to the active site that accommodates the substrate, also have a second binding site, called precisely allosteric site that binds the allosteric effectors that can be distinguished in: allosteric inhibitors allosteric activators The action of these second molecules of ligand, can only be explicated if the active site is free and vice versa, because of the conformational changes induced by both the bonds.
1) Activation by proteolytic cuts 2) Activation by a union with a cofactor 3) Assembly with a sub-unit 4) intracellular translocation 5) Activation / Inactivation by changing electric charges 6) allosteric regulation Example of metabolic chain Feedback regulation
We have seen how the enzymes are regulated. However, among the huge amount of enzymes that are present in the cells of our body, there are some that are not regulated. This means that the cell only needs to produce that particular enzyme to automatically obtain the products of the chemical reaction that will catalyze the enzyme in question. It simply acts as an ON / OFF switch These enzymes are defined as having constitutive activity A concrete example is represented by catecholaminergic neurons. Some of these neurons can synthesize an enzyme called dopamine-b-hydroxylase, which catalyzes a transformation of dopamine into noradrenaline, and are then said noradrenergic neurons. Other neurons do not encode this enzyme, and thus does not host this reaction and the dopamine remains... Dopamine.