ISOMERASES: PROCESSES, FUNCTIONS, NOMENCLATURE AND SUB-CLASSES - BIOLOGY - 2025

The isomerases are a class of enzymes involved in the rearrangement of structural or positional isomers and stereoisomers of different molecules. They are present in virtually all cellular organisms, fulfilling functions in various contexts.

Enzymes of this class act on a single substrate, despite the fact that some may be covalently associated with cofactors, ions, among others. The general reaction, therefore, can be seen as follows:

XY → YX

The reactions catalyzed by these enzymes involve an internal rearrangement of the bonds, which can mean changes in the position of functional groups, in the position of double bonds between carbons, among others, without changes in the molecular formula of the substrate.

Mechanism of action of Isopentenyl Pyrophosphate Isomerase catalyzing the isomerization of isopentenyl pyrophosphate to dimethylallyl pyrophosphate (Source: Yjlu22 via Wikimedia Commons)

The isomerases fulfill diverse functions in great variety of biological processes, within which it is possible to include metabolic pathways, cell division, DNA replication, to name a few.

Isomerases were the first industrially used enzymes for the production of syrups and other sugary foods, thanks to their ability to interconvert the isomers of different types of carbohydrates.

Biological processes in which they participate

Isomerases participate in multiple vital cellular processes. Among the most prominent are DNA replication and packaging, catalyzed by topoisomerases. These events are crucial for nucleic acid replication, as well as for its condensation prior to cell division.

Glycolysis, one of the central metabolic pathways in the cell, includes at least three isomeric enzymes, namely, phosphoglucose isomerase, triose phosphate isomerase, and phosphoglycerate mutase.

The conversion of UDP-galactose to UDP-glucose in the galactose catabolism pathway is accomplished by the action of an epimerase. In humans this enzyme is known as UDP-glucose 4-epimerase.

Protein folding is an essential process for the function of many enzymes in nature. The protein-disulfide isomerase enzyme assists in the folding of proteins containing disulfide bridges by modifying their position in the molecules that it uses as substrate.

Features

The main function of enzymes belonging to the class of isomerases can be seen as transforming a substrate through a small structural change, in order to make it susceptible to further processing by enzymes downstream in a metabolic pathway, for example.

An example of isomerization is the change from the phosphate group in position 3 to the carbon in position 2 of the 3-phosphoglycerate to convert it into 2-phosphoglycerate, catalyzed by the enzyme phosphoglycerate mutase in the glycolytic pathway, thereby generating a higher energy compound which is a functional substrate of enolase.

Nomenclature

The classification of isomerases follows the general rules for the classification of enzymes proposed by the Enzyme Commission in 1961, in which each enzyme receives a numerical code for its classification.

The position of the numbers in said code indicates each of the divisions or categories in the classification and these numbers are preceded by the letters "EC".

For isomerases, the first number represents the enzyme class, the second denotes the type of isomerization they perform, and the third the substrate on which they act.

The nomenclature of the class of isomerases is EC.5. It has seven subclasses, so enzymes with the code from EC.5.1 to EC.5.6 will be found. There is a sixth "sub-class" of isomerases known as "other isomerases", whose code is EC.5.99, since it includes enzymes with various isomerase functions.

The denotation of the subclasses is done mainly according to the type of isomerization that these enzymes perform. Despite this, they can also receive names such as racemases, epimerases, cis-trans -isomerases, isomerases, tautomerases, mutases or cyclo isomerases.

Subclasses

There are 7 classes of enzymes within the isomerase family:

EC.5.1 Racemases and epimerases

They catalyze the formation of racemic mixtures based on the position of the α-carbon. They can act on amino acids and derivatives (EC.5.1.1), on hydroxy acid groups and derivatives (EC.5.1.2), on carbohydrates and derivatives (EC.5.1.3) and others (EC.5.1.99).

EC.5.2

They catalyze the conversion between the cis and trans isomeric forms of different molecules.

EC.5.3 Intramolecular isomerases

These enzymes are responsible for the isomerization of internal portions in the same molecule. There are some that carry out redox reactions, where the electron donor and acceptor is the same molecule, so they are not classified as oxidoreductases.

They can act by converting aldoses and ketoses (EC.5.3.1), on keto- and enol- groups (EC.5.3.2), changing the position of CC double bonds (EC.5.3.3), of SS disulfide bonds (EC.5.3.4) and other “oxidoreductases” (EC.5.3.99).

EC.5.4 Intramolecular transferases (mutases)

These enzymes catalyze the positional changes of various groups within the same molecule. They are classified according to the type of group they "move".

There are the phosphomuttases (EC.5.4.1), those that transfer amino groups (EC.5.4.2), those that transfer hydroxyl groups (EC.5.4.3), and those that transfer other types of groups (EC.5.4. 99).

EC.5.5 Intramolecular lyases

They catalyze the "elimination" of a group that is part of a molecule, but is still covalently bound to it.

EC.5.6 Isomerases that alter macromolecular conformation

They can act by altering the conformation of polypeptides (EC.5.6.1) or nucleic acids (EC.5.6.2).

EC.5.99 Other isomerases

This subclass brings together enzymes such as Thiocyanate isomerase and 2-hydroxychrome-2-carboxylate isomerase.

References

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