Structural Biochemistry/Enzyme Regulation
Homeostasis is the mechanism by which an organism maintains its body in dynamic equilibrium. A slight change in a concentration of a fluid within the organism may cause major changes within its body. In living cells, there are different kinds of enzymes working together. Living cells synthesis or break down molecules for normal metabolism and growth. Enzyme regulation is one example. Enzymes are used to catalyze (speed up) reactions within the body. The regulation of enzymes help maintain the body's equilibrium. An enzyme can be in either one of two modes: on or off. That is controlling the synthesis of enzymes and controlling the activity of enzymes (feedback inhibition). Basically enzyme regulation takes advantage of these two modes. When a concentration of one product is too high, a negative feedback loop can occur and stop the enzyme that catalyzes that specific product. Enabling a lowering of reaction rate and lowering the concentration over time.
Enzymes activities are regulated by five basic techniques.
1. Allosteric control. Allosteric proteins have different regulatory and catalytic binding sites. Allosteric proteins are cooperative proteins, where binding of a substrate in one active site affects the activity of the rest of the binding sites. Some substrate binding will favor the protein to be in the inactive T (tense) state, while other substrate binding will favor the protein to be in the active R (relaxed) state, depending on the biological needs. Allosterically regulated enzymes do not however obey Michaelis-Menten kinetics but instead follow sigmoidal kinetics.
Example of allostery:[]
2. Isoenzymes. Isoenzymes have different animo acid sequences but catalyze the same reaction as enzymes. They usually have different Km and Vmax values, and different regulatory techniques. The advantages of isoenzymes is that it can catalyze the same reaction under the different environments within the different organelles. Isozymes are an important entity in metabolism for servicing a specific tissue or developmental sequence. For example lactate dehydrogenase (LDH) has two isozymes that have an amino acid sequence that is 75% similar. The H isozyme is present in the heart muscle and the M isozyme is expressed in the skeletal muscle.
Example of isoenzymes and their structure: []
3. Reversible covalent modification. An enzyme's activity can be altered by covalently attaching a different group to its active site. It blocks the natural substrate from binding to the active site. The most common forms of covalent modification are phosphorylation and dephosphorylation as well as aceylation and deacylation. Not all forms of covalent modification are readily reversible. For example, an attachment of a lipid group will inhibit the signal-transduction pathway in some proteins.
Example of dephosphorylation: []
4. Proteolytic Activation. Many enzymes are present in the body in their inactive forms call zymogen or proenzyme. They are not activated until a digestive enzyme cleaves it. The cleavage alters the three dimension shape of the enzyme, forming the active site in the right orientation. The zymogens become active enzymes in an irreversible reaction, typically the hydrolysis of bonds in the zymogen.
Example of zymogen structure: []
5. Control by Limiting Amount of Enzyme. The amount of enzymes gets produced can be controlled at the transcription level.
In Double Displacement (Ping Pong reaction), two compounds switch places to form new compounds. Two reactants yield two products.
Ping Pong MechanismEdit
In the Ping Pong mechanism substrate S binds to the enzyme transferring a chemical component to the active site making a modified enzyme. Once substrate S leaves active site substrate T can bind and react with the newly modified active site. Once the newly formed product leaves the enzyme it returns to its original state ready to accept substrate S.
Enzymes that exhibit this mechanism include thioredoxin peroxidase, cytydilytransferase, and chymotrypsin. Serine proteases which cleave polypeptide bonds is an example of this mechanism where the enzyme accepts the amino acid and modifies the serine residue by acetylating it. The modified enzyme accepts water as which liberates the product and liberates the original enzyme.
In Ping-Pong Reactions, one or more products are released before all substrates bind the enzyme. The defining feature of double-displacement reactions is the existence of a substituted enzyme intermediate, in which the enzyme is temporarily modified. Reactions that shuttle amino groups between amino acids and a-ketoacids are classic examples of double displacement mechanisms. The enzyme aspartate aminotransferase catalyzes the transfer of an amino group from aspartate to a-ketoglutarate.
After aspartate binds to the enzyme, the enzyme accepts aspartate’s amino group to form the substituted enzyme intermediate. The first product, oxaloacetate, subsequently departs. The second substrate, a-ketoglutarate, binds to the enzyme, accepts the amino group from the modified enzyme, and is then released as the final product, glutamate. In the Cleland notation, the substrates appear to bounce on and off the enzyme analogously to a Ping-Pong ball bouncing on a table.
The potential threatsEdit
As scientific researchers have proved that enzymes are central for metabolic pathways in organisms, they have also pointed out that those very enzymes could also potentially threaten the survival of the organisms. For example, in DNA transcription, if the enzyme carrying out the work malfunctions, it can give rise to an errant gene that codes faulty proteins or no proteins at all (these occurrences are known as mutations). Therefore, such proteins may result in out-of-control cell divisions, which can lead to dire consequences, which most of the time are related to cancer.
Enzymes play a vital role in organisms' ability for survival. They create the abilities of moving, thinking, sensing, and so on. Besides, enzymes are central for almost any metabolic reactions in any organisms: they can catalyze a series of lengthening lab-conducting chemical reactions in seconds with high levels of complexity and precision, thus earning the name "natural catalysts". Biochemists' goals are trying to study and understand the mechanisms, by which only such enzymes can do their wonderful magic for organisms' survivability.