Difference Between Coenzyme and Cofactor

The key difference between coenzyme and cofactor is that the coenzymes are organic molecules, whereas the cofactors can be either organic or inorganic molecules.

Enzymes are essential biological macromolecules. They are the biological catalysts, which increases the rate of biological reactions under very mild conditions.

Moreover, enzymes are proteins; thus, when they are subjected to a high level of heat, salt concentrations, mechanical forces, organic solvents and concentrated acid or base solutions, they tend to denaturize. Sometimes, enzymes need the support of another molecule or an ion to have the specific function. Coenzymes and cofactors are such molecules.

What is Coenzyme?

Coenzymes are smaller organic molecules than the enzyme (which is a protein). They are mainly organic molecules, and many of them derive from vitamins. For instance, niacin produces the coenzyme NAD+ that is responsible for oxidation reactions.

Further, coenzyme A is made from pantothenic acid, and they participate in reactions as acetyl group carriers. Coenzymes are a type of cofactors. However, coenzymes bind loosely with the enzyme while there are some other cofactors, which binds tightly to the enzyme.

What is Cofactor?

Cofactors are the assisting chemical species (a molecule or an ion), which binds with enzymes in order to bring out the enzyme’s biological activity. Most of the enzymes need cofactors to exert their activity, whereas some enzymes may not need them.

An enzyme without the cofactor is an apoenzyme. When an apoenzyme is together with its cofactor, we call it as a holoenzyme. Further, some enzymes may associate with one cofactor while some may associate with several cofactors.

Without the cofactors, the enzyme activity will be lost. We can divide these molecules broadly into two groups as organic cofactors and inorganic cofactors. Inorganic ones mainly include metal ions. However, these metal ions are often needed in trace amounts.

For instance, magnesium is essential for hexokinase, DNA polymerase and Glucose-6-phosphate enzymes while zinc is an essential metal ion for alcohol dehydrogenase, carbonic anhydrase and DNA polymerase function.


Other than magnesium and zinc, there are other metal ions like cupric, ferrous, ferric, manganese, nickel etc., which associates with different types of enzymes. Metal ions in enzymes can participate in the catalytic process in three major ways.

  • By binding to the substrate as to orient it properly for reaction
  • And, by electrostatically stabilizing or shielding negative charges
  • By facilitating oxidation, reduction reaction through reversible changes in the metal ions’ oxidation state

Moreover, organic cofactors are mainly vitamins and other non-vitamin organic molecules like ATP, glutathione, heme, CTP, coenzyme B, etc. We can divide organic cofactors further into two groups as the coenzyme and the prosthetic group.

Prosthetic groups bind tightly with the enzyme and participate in the enzyme catalysis reaction. During the reaction, the enzyme- prosthetic group complex may undergo structural changes, but they are coming to the original state when the reaction is over. FAD is a prosthetic group of succinate dehydrogenase enzyme, which reduces to FADH2 in the process of converting succinate to fumarate.

What is the Difference Between Coenzyme and Cofactor?

A coenzyme is an organic non-protein compound that binds with an enzyme to catalyze a reaction while a cofactor is a substance (other than the substrate) whose presence is essential for the activity of an enzyme.

Hence, Coenzymes are a type of cofactors. The key difference between coenzyme and cofactor is that the coenzymes are organic molecules, whereas the cofactors can be either organic or inorganic molecules.

Moreover, the coenzymes are bound loosely with the enzyme, but there are some other cofactors, which are bound tightly to the enzyme. Other than that, the coenzyme can be removed from the enzyme easily while cofactor can only be removed by denaturing the enzyme. So, this is another difference between coenzyme and cofactor.

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