What difference cofactor, coenzyme and prosthetic group?

When we talk about cofactors, we quickly think of enzymes, coenzymes, and if you have a background in biochemistry, you might also think of prosthetic groups. All these terms are closely related and differentiating them is not always easy. In this article we will try to clearly define what a cofactor is, what types exist and what characteristics are specific to each one.

Forget the definitions that differentiate a cofactor from a coenzyme according to its inorganic or organic nature. Although these definitions are very common on the Internet, they are wrong definitions.

What is a cofactor?

A cofactor is defined as all non-protein substance that is required for a protein to exert its biological activity. Most of the time this protein is an enzyme, hence the term cofactor is used practically as a synonym for enzymatic cofactor, but it must be clear that they are not exactly the same since a cofactor can exert its function in a non-enzymatic protein. .

enzyme cofactors

Practically 100% of the metabolic reactions that occur at all times in the cells of our body are catalyzed by enzymes, organic protein macromolecules that increase the speed of chemical reactions that would occur very slowly without their action.

Each enzyme needs very specific conditions for optimal functioning and are very sensitive to small changes in temperature, pH, concentration of substrate and product, concentration of the enzyme itself, and other physicochemical variables.

The activity of enzymes can also be affected by the presence of other substances. Substances that inhibit the action of enzymes are known as enzyme inhibitors, while substances that enhance their activity are known as enzyme inhibitors. enzyme activators. Activators increase the rate of enzymatic reactions but they do not necessarily have to be required for the enzyme to show activity.

However, some enzymes necessarily need other substances to show their activity or catalyze some specific reaction. It could be said that these enzymes need "obligatory activators" and it is these obligatory activators that are called cofactors. Cofactors can be of a very varied nature and characteristics, from small monatomic metal ions to organic molecules of a certain complexity such as coenzymes and prosthetic groups.

So, a coenzyme and prosthetic group are two types of cofactors. Let's see in more detail what each of them is and what characteristics define them.

Types of cofactors

Cofactors can be classified according to different criteria, one of the most common is according to their organic or inorganic nature:

  • inorganic cofactors: metal ions (Mg2+Cu+,Mn2+) and the iron-sulfur centers.
  • organic cofactors: coenzymes, for example flavin, and prosthetic groups, for example the heme group. As we will see below, the differentiation between coenzyme and prosthetic group is somewhat diffuse and there are authors who propose the use of only one of the two terms and abandon the other.

Inorganic cofactors: metal ions and iron-sulfur centers

Metal ions are very common cofactors and the most frequent of these are metal ions composed of one or two atoms. In humans, the list of these cofactors frequently includes iron, magnesium, manganese, cobalt, copper, zinc, and molybdenum, all of which essential trace elements in our diet precisely due to their role as cofactors.

Some inorganic elements participate in the allosteric regulation of enzymes but are not considered cofactors of the enzymes they regulate. For example, calcium participates in the allosteric regulation of nitric oxide synthase, protein phosphatase or adenylate kinase, among many others, but it is not a cofactor of these enzymes.

Another type of inorganic cofactors are the iron-sulfur centers. These centers are complexes formed by sulfide groupsusually from the amino acid cysteine, attached to two or four iron atoms. In addition to their functional role as cofactors, the iron-sulfur centers play a fundamental structural role in the spatial conformation of the protein. Some examples of proteins with iron-sulfur centers are ferredoxin, NADH dehydrogenase or Coenzyme Q – cytochrome c reductase.

Some cofactors include inorganic elements bound to organic molecules. These cofactors are usually included in the group of organic cofactors due to the greater weight of the organic fraction. For example the heme group.

Organic cofactors: coenzymes and prosthetic groups

Coenzymes and prosthetic groups are two specific types of cofactors that are organic in nature. They tend to be small molecules, usually with a mass of less than 1000 Da. To differentiate between the two, the strength or type of bond between the cofactor and the protein is usually taken into account: a coenzyme binds weakly while a prosthetic group binds strongly and generally cannot be separated from the protein if it is not denatured. .

This differentiation between coenzyme and prosthetic group is not very clear since there is no exact definition between what is a strong bond and weak bond. Furthermore, the same cofactor can bind weakly to one protein and more strongly to another. Even some substances traditionally considered to be coenzymes have a covalent bond to their enzymewhich would go against this definition as a clearly strong union type.

The only obvious difference is that the term coenzyme refers specifically to enzyme cofactors while prosthetic groups can be protein cofactors without enzyme activity. To end this confusion and have an exact definition, some authors have proposed abandoning the term coenzyme in favor of prosthetic group to refer to all organic cofactors in general and use coenzyme to refer specifically to enzymatic organic cofactors.

The use of the term cofactor has also been proposed to name a substance other than the protein and the substrate that is required for protein activity, and the use of the term prosthetic group to name substances that remain covalently bound to the protein. throughout the catalytic cycle. A coenzyme could fall into both groups depending on the mode of action. In any case, there is still no unequivocal consensus adopted by the scientific community.

Examples of coenzymes and prosthetic groups

The most common examples of coenzymes are vitamins and derivatives. Not all vitamins act as coenzymes but it is a very frequent activity among them. In the group of B vitamins we find numerous examples, such as coenzyme A, which is a derivative of pantonenic acid (vitamin B5), or the NAD cofactors+ and NADP+which are derivatives of niacin (vitamin B3).

The heme group is a typical example of a prosthetic group. In general, the proteins that contain the heme group are known as hemoproteins. This group includes proteins with important biological functions. For example, hemoglobin and myoglobin (involved in the transport of Otwo), several cytochromes (involved in the transport of chemical energy) or the enzymes catalase and endothelial nitric oxide synthase.

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