Enzyme mechanism of action and Enzyme specificity

Enzymes and Enzyme specificity

Enzyme, a substance that acts as a catalyst in living organisms, regulating the rate at which chemical reactions proceed without itself being altered in the process.Enzymes are giant macromolecules which catalyse biochemical reactions. They are remarkable in many ways. Their three-dimensional structures are highly complex, yet they are formed by spontaneous folding of a linear polypeptide chain. Their catalytic properties are far more impressive than synthetic catalysts which operate under more extreme conditions.The most striking characteristics of enzymes are their catalytic power and specificity. Catalysis takes place at a particular site on the enzyme called the active site. Nearly all known enzymes are proteins. The discovery of catalytically active RNA molecules provides compelling evidence that RNA was an early biocatalyst, the ribozyme. Most reactions in biological systems do not take place at perceptible rates in the absence of enzymes. Enzymes are highly specific both in the reactions that they catalyze and in their choice of reactants, which are called substrates. An enzyme usually catalyzes a single chemical reaction or a set of closely related reactions.The catalytic activity of many enzymes depends on the presence of small molecules termed cofactors, although the precise role varies with the cofactor and the enzyme. Such an enzyme without its cofactor, the protein part is referred to as anapoenzyme; the complete, catalytically active enzyme is called a holoenzyme. Cofactors can be subdivided into two groups: metals and small organic molecules. The enzyme carbonic anhydrase, for example, requires Zn2+ for its activity. Glycogen phosphorylase, the enzyme which mobilizes glycogen for energy, requires the small organic molecule pyridoxal phosphate (PLP) which is a derivative of pyridoxine (Vit B complex). Cofactors that are small organic molecules are called coenzymes. Often derived from vitamins, coenzymes can be either tightly or loosely bound to the enzyme. If tightly bound, they are called prosthetic groups. Loosely associated coenzymes are more like co-substrates because they bind to and are released from the enzyme just as substrates and products are.


 1.A coenzyme - a non-protein organic substance which is dialyzable, thermostable and loosely attached to the protein part.

2. A prosthetic group - an organic substance which is dialyzable and thermostable which is firmly attached to the protein or apoenzyme portion.

3. A metal-ion-activator - these include K+, Fe++, Fe+++, Cu++, Co++, Zn++, Mn++, Mg++, Ca++, and Mo+++.

Mechanism of Enzyme action

An enzyme attracts substrates to its active site, catalyzes the chemical reaction by which products are formed, and then allows the products to dissociate. The combination formed by an enzyme and its substrates is called the enzyme–substrate complex. The substrates interact with the active site of enzyme by noncovalent weak interactions like electrostatic or hydrophobic interactions. As the enzyme molecule remains unchanged after the reaction, a small amount of enzyme can turn over a large amount of substrate to product.



Mechanism of Enzyme action


Fig: www.biologydiscussion.com

Enzymes are very specific and Emil Fischer in 1894 suggested that in lock-and-key model, the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another. Like a key into a lock, only the correct size and shape of the substrate would fit into the active site of the enzyme. The induced fit model suggested by Daniel Koshland in 1958 suggests that the active site continues to change until the substrate is completely bound to the active site of the enzyme, at which point the final shape and charge is determined. The aminoacids which make up the active site are moulded into precise shape which enables enzyme to perform catalytic function more effectively. Unlike the lock-and-key model, the induced fit model explains the flexibility of enzymes. Lock and key hypothesis shows the high specificity of enzymes. However, it does not explain the stabilization of the transition state that the enzymes achieve. Once formed, the products no longer fit into the active site of enzyme and moves to the surrounding medium leaving the active site so that further substrate molecules can bind to the active site. 


http://chemistry.elmhurst.edu

Specificity of Enzymes

One of the properties of enzymes that makes them so important as diagnostic and research tools is the specificity they exhibit relative to the reactions they catalyze. A few enzymes exhibit absolute specificity; that is, they will catalyze only one particular reaction. Other enzymes will be specific for a particular type of chemical bond or functional group. Specificity indicates selectivity of enzyme to their substrate. Specificity is the ability of an enzyme to choose exact substrate. It is mainly based on structural complementarities of an enzyme.


·Absolute specificity - the enzyme will catalyze only one reaction.eg: Glucokinase phosphorylates only glucose and not any other monosaccharides.

  • Group specificity - the enzyme will act only on molecules that have specific functional groups, such as amino, phosphate and methyl groups. Eg: Trypsin hydrolyse the peptide bond in which amino group is contributed by  basic aminoacids

Hexokinase catalyse the phosphorylation of not only glucose but also other hexoses like mannose, fructose and glucosamine.

  • Linkage specificity or bond specificity - the enzyme will act on a particular type of chemical bond regardless of the rest of the molecular structure. Eg: Amylase can hydrolyse α1-4 glycosidic bonds of both starch and glycogen.

Lipase hydrolase the ester bond between fattyacid and glycerol in any fats

Proteinases hydrolase peptide bond between aminoacids in any proteins

  • Stereospecificity - the enzyme will act on a particular steric or optical isomer. Here specificity is very high. Enzymes are specific not only to its substrate but also its optical configuration eg: L-aminoacid oxidase acts only on L aminoacids

α Amylase can act only on starch (α 1-4 Glycosidic bond) not on cellulose which has β 1-4 glycosidic bond.


  • Geometrical specificity

Here specificity is less. Here specificity can be due to molecular geometry. Enzymes can act different substrates having similar molecular geometry. Geometric specificities are more accurately described as preferances.

Eg: Alcohol dehydrogenase can catalyse the oxidation of ethanol, methanol and propanol to give corresponding aldehydes. But the specificity is more for ethanol than other alcohols. Here the enzyme prefers ethanol. That is why patients from alcohol poisoning are treated with ethanol since the product acetaldehyde formed is less toxic compared to formaldehyde produced from methanol.

Note: Figures adapted from easy biology classes.

  • Cofactor specificity

A cofactor is a non-proteinchemical compound or metallic ion that is required for an enzyme's activity as a catalyst, a substance that increases the rate of a chemical reaction. Cofactors can be considered "helper molecules" that assist in biochemical transformations. Cofactors can be divided into two types: inorganic ions and complex organic molecules called coenzymes. Inorganic cofactors include the metal ions Mg2+, Cu+, Mn2+ and iron-sulfur clusters. Coenzymes are mostly derived from vitamins and other organic essential nutrients in small amounts. Coenzymes are further divided into two types. The first is called a "prosthetic group", which consists of a coenzyme that is tightly or even covalently, and permanently bound to a protein. The second types of coenzymes are called "co-substrates", and are transiently bound to the protein.

Haem is an iron containing prosthetic group. Haem is the prosthetic group of cytochromes where it acts as an electron carrier. In accepting electrons, the iron is reduced to Fe (II) and in handing on electrons it is oxidized to Fe (III). It takes part in oxidation- reduction reaction by reversible changes in the valency of iron.

Cu2+, Fe3+, Zn2+ etc are some examples of cofactors. Cd2+ and Hg2+ can replace Zn2+ making these enzymes inactive resulting in heavy metal poisoning.

Coenzymes usually participate in acid-base reactions and form transient covalent bonds and take part in Charge-charge interactions. Coenzymes act as cosubstrates. Eg: PLP in transaminases, NAD+ is an obligatory oxidizing agent in alcohol dehydrogenase reaction.


Cofactors can act as chemical teeth.

Nicotinamide adenine dinucleotide (NAD) is a coenzyme for a great number of dehydrogenase reactions in which it acts as a hydrogen acceptor. Among them are the alcohol dehydrogenase, malate dehydrogenase and lactate dehydrogenase reactions.

Order of specificity

Geometric specificity < Bond specificity < Group specificity < Absolute substrate specificity < Cofactor specificity < Stereo specificity


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