Isomerases

Isomerases are enzymes that catalyse modifications inside a single molecule. This means that the end product has the same chemical formula as the starting material but a different physical structure than it did at the starting point. 

The following is the general structure of such a reaction:

A–B → B–A

There is only one substrate that results in a single finished product. Even though this product has the same molecular formula as the substrate, the bond connectivity and spatial arrangement of the molecules are different. Isomerases are enzymes that catalyse reactions in a wide range of biological activities, including glycolysis and carbohydrate metabolism, among others.

Isomers themselves come in a variety of forms, but they can be broadly divided into two categories: structural isomers and stereoisomers. Structural isomers differ from one another in that they have a distinct ordering of bonds and/or different bond connectivity, as in the case of hexane and its four other isomeric forms, for example (2-methyl pentane, 3-methyl pentane, 2,2-dimethyl butane, and 2,3-dimethylbutane).

Racemases, epimerases, and cis-trans isomers are examples of enzymes that catalyse the interconversion of stereoisomers, which are found in the subcategories of isomerases that contain them. Molecular lyases, oxidoreductases, and transferases are enzymes that catalyse the interconversion of structural isomers within the same molecule. Somerases can speed up the reaction rate by decreasing the isomerization energy required for it to occur.

Classification Of Isomerases 

EC 5 is the classification category for enzymes that catalyse isomerase-catalyzed processes. There are six sub-classes of isomerase, which can be further subdivided as follows:

Racemases/Epimerases

While racemases work on compounds that include just one chiral carbon, epimerases act on molecules that have multiple chiral carbons but only on one of them. This category is then further subdivided based on the substrate that the enzyme works on, for example, action on amino acids versus activity on carbohydrates.

Cis-trans Isomerases

This class includes the isomerases that catalyse the isomerization of the cis-trans isomers. Cis-trans Isomerases: This class includes the isomerases that catalyse the isomerization of the cis-trans isomers. Certain alkenes and cycloalkanes may include cis-trans stereoisomers. Instead of using absolute configuration to separate these isomers, the substituent groups are positioned about the plane of reference, allowing them to be distinguished from one another. Trans isomers have their substituent groups on the same side of the molecule as cis isomers, whereas cis isomers have their substituent groups on opposing sides of the molecule. This class does not have any sub-classes, and it does not have any children.

Intramolecular Oxidoreductase

These isomerases act by catalysing the transfer of electrons from one molecule to another, which is known as intramolecular oxidoreductase. For the most part, they catalyse the reaction that oxidises one portion of the molecule and reduces the other component of the molecule. Intramolecular oxidoreductases can be classified into further sub-classes based on the processes that they perform.

Intramolecular Transferases (mutases)

Intramolecular transferases (mutases) are enzymes that are utilised to catalyse the transport of functional groups from one portion of a molecule to another inside the same molecule. There are several sub-classifications of intramolecular transferases, each based on which functional group the enzyme is moving through.

In addition to the aforementioned enzymes, intramolecular lyases are also present and perform their functions when a group is deemed to be removed from one part of the molecule that is involved in the formation of a double bond while still being covalently linked to the molecule in question. In some cases, intramolecular lyases are involved in the dismantling of ring structures, which is why they are used. This category cannot be subdivided any further.

Mechanisms Of Isomerases

Ring Expansion and Contraction Through the Use of Tautomers

The isomerisation of glucose to fructose is an example of this type of reaction, which involves the opening and closing of a ring. Because of acid/base catalysis, the overall reaction causes the ring to form an aldose, which is followed by the formation of an intermediate known as cis-ethanol. Following the creation of a ketose, the ring is sealed.

Epimerization

The Calvin cycle, in which D-ribulose-5-phosphate is transformed into D-xylulose-5-phosphate by ribulose-phosphate3-epimerase, is a classic example of epimerization. The difference between the substrate and the product is found in the stereochemistry of the third carbon in the chain, which is present in both. The deprotonation of the third carbon results in the formation of a reactive enolate intermediate in the reaction.

Intramolecular Transfer

 Chorismate mutase is an example of an intramolecular transferase, which is a type of enzyme that transfers between molecules. Chorismate mutase is a protein that catalyses the conversion of chorismate to prephenate. In some plants and bacteria, the latter is employed as a precursor for the amino acids L-tyrosine and L-phenylalanine. This reaction is a Claisen modification that can proceed with or without the isomerase; however, the rate increases by a factor of 10 6 as a result of the presence of the chorismate mutase. The process enters a chair transition state, with the substrate in a trans-diaxial position, as the result of this posture.

Intramolecular Oxidoreduction

In the synthesis of cholesterol, the activity of Isopentenyl diphosphate delta isomerase type I (also known as IPP isomerase) serves as an excellent illustration of this reaction process. This enzyme is most commonly used to catalyse the conversion of isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMAPP). During this isomerization process, a stable carbon-carbon double bond is repositioned, resulting in the formation of an allylic isomer that is deeply electrophilic. This process is catalysed by the stereoselective antarafacial transposition of a single proton, which is catalysed by IPP isomerase.

EXAMPLES OF ISOMERASES

• Isomerases comprise a variety of enzymes such as triosephosphate isomerase, bisphosphoglycerate mutase, and photoisomerase, among others.

• When used in conjunction with other enzymes, isomerases can assist prepare a molecule for subsequent processes such as oxidation-reduction reactions. 

• As an example, during the conversion of citrate to isocitrate in the citric acid cycle, isomerization is used to prepare the molecule for further oxidation and decarboxylation by moving the hydroxyl group of citrate from the third to the second position of the citrate molecule. 

• It should also be noted that isomerases are capable of catalysing phosphorylation reaction pathways across the Krebs Cycle since they prepare the molecule for different oxidation states. 

• Isomerases make it possible to shift the location of the substrate or product while maintaining the overall chemical composition of the substrate or product.

Conclusion

When it comes to biology, isomerization reactions are essential, and isomers typically differ in terms of their biological function and pharmacological effects. In this study, we used a combination of manual and computational methodologies to catalogue the isomerization reactions that are known to occur in biology. This method provides a solid foundation for comparing and categorising reactions into groups using a comprehensive methodology. Our comprehension of the biology of isomerization is furthered by comparing our findings with those of the Enzyme Commission (EC), which is the conventional way to represent enzyme function based on the entire chemistry of the catalysed reaction. The classification of reactions involving stereoisomerism is straightforward, with two distinct types (racemases/epimerases and cis-trans isomerases) to choose from; however, reactions involving structural isomerism are diverse and difficult to categorise using a hierarchical approach because of their complexity. Isomers are used in the production of sugar, which is by far the most prevalent industrial application for them. In addition to its other names, glucose isomerase (also known as xylose isomerase) is responsible for the conversion of D-xylose and D-glucose to their respective sugars, D-xylulose and D-fructose. The interconversion of aldoses and ketoses is catalysed by glucose isomerase, as is the case with other sugar isomerases.