Difference between coenzyme and cofactor

Key difference - coenzyme vs. cofactor

A unique set of biochemical reactions that occur in a particular cell defines that cell's identity among the other cells. Enzymes are proteins that catalyze these biochemical reactions. Both coenzymes and cofactors are small, non-proteinaceous substances that play an important role in the cell's metabolic functions by helping enzymes catalyze biochemical reactions. They bind to the active center of the enzyme. The main difference between coenzyme and cofactor is that coenzyme is a type of cofactor that binds loosely to the enzyme, while cofactor sometimes binds tightly to the enzyme.

This article is about,

1. What is a coenzyme - definition, properties, functions, examples 2. What is a cofactor - definition, properties, functions, examples 3. What is the difference between coenzyme and cofactor

Difference Between Coenzyme And Cofactor - Summary Of The Comparison

What is a coenzyme?

Any freely diffusing organic molecule that serves as a cofactor with enzymes by supporting the enzyme's function is called a coenzyme. Therefore, coenzyme is a small, organic, non-protein molecule that occurs in the cell. Coenzymes act as intermediate carriers of electrons, certain atoms or functional groups that are to be transferred during the catalyzing reaction. For example, NAD transfers electrons in coupled oxidation-reduction reactions.

Coenzymes are modified during the reaction and another enzyme is needed to restore the coenzyme to its original state. Since coenzymes are chemically changed during the reaction, they are considered to be the enzyme's second substrates. This is why coenzymes are also referred to as co-substrates . On the other hand, since coenzymes are regenerated in the body, their levels in the body should be maintained. Most of the B vitamins are coenzymes that transfer atoms or groups of atoms between molecules during the synthesis of carbohydrates, proteins and fats. These vitamins should be ingested through food as the body cannot synthesize them. Some of the coenzymes and the reactions they are involved in are listed in Table 1 .

Coenzymes and their functions


Transfer entity

NAD (nicotine adenine dinucleotide)

Electron (hydrogen atom)

NADP (nicotine adenine dinucleotide phosphate)

Electron (hydrogen atom)

FAD (flavin adenine dinucleotide) (Vit.B2)

Electron (hydrogen atom)

CoA (Coenzyme A)

Acyl groups

CoQ (Coenzyme Q)

Electrons (hydrogen atom)

Thiamine (thiamine pyrophosphate) (vit. B1)


Pyridoxine (pyridoxal phosphate) (vit B6)

Amino groups


Carbon dioxide

Carbamide coenzymes (vit. B12)

Alkyl groups

Difference between coenzyme and cofactor

Figure 1: Hydrogen transfer by DHFR from NADPH

What is a cofactor?

Cofactor is a non-protein chemical compound that binds tightly to the enzyme and supports the function of an enzyme. It binds to the inactive form of the enzyme known as an apoenzyme, which makes the enzyme active. Therefore, cofactors are called helper molecules . The active form of the enzyme is called a holoenzyme. Cofactors can be either metals or coenzymes. Inorganic substances such as metal that bind firmly to the enzyme and cannot be removed without denaturing are called prosthetic groups. Metals like iron and copper are prosthetic cofactors. Some enzymes only work if a covalently bound metal ion is available in their active site. Coenzymes are organic cofactors that bind loosely to the enzyme. Some enzymes that require metal ions for their function are listed in Table 2.

Enzymes that need metal ions for their function


Enzyme or protein

Zn2 +

Carbonic anhydrase

Zn2 +

Alcohol dehydrogenase

Fe 2+ or Fe 3+

Cytochrome, hemoglobin

Fe 2+ or Fe 3+


Cu + or Cu 2+

Cytochrome oxidase

K + and Mg 2+

Pyruvate phosphokinase

Difference between coenzyme and cofactor

Figure 2: Mg2 + ions in the active center of the enolase

Difference between coenzyme and cofactor


Coenzyme: Coenzyme is a small, organic, non-protein molecule that carries chemical groups between enzymes.

Cofactor: Cofactor is a non-protein chemical compound that binds tightly and loosely to an enzyme or other protein molecules.


Coenzyme: Coenzyme is a type of cofactor.

Cofactor: Two types of cofactors are found: coenzymes and prosthetic groups.

Molecule / compound

Coenzyme: Coenzymes are molecules.

Cofactor: Cofactors are chemical compounds.

Organic / inorganic compounds

Coenzyme: Coenzymes are organic molecules.

Cofactor: Cofactors are inorganic compounds.


Coenzyme: Coenzymes are loosely bound to enzymes.

Cofactor: Cofactors such as metal ions are covalently bound to an enzyme.


Coenzyme: Coenzymes support biological transformations.

Cofactor: Cofactors support the function of the respective enzyme.


Coenzyme: Coenzymes serve as carriers for the enzymes.

Cofactor: Cofactors increase the reaction rate, which is catalyzed by the respective enzyme.


Coenzymes: Coenzymes can be easily removed from the enzyme because they are loosely bound to the enzyme.

Cofactor: Cofactors can only be removed by denaturing the enzyme.


Coenzyme: Vitamins, biotin, coenzyme A are coenzymes.

Cofactor: Metal ions such as Zn 2+ , K + and Mg 2+ are cofactors.


Coenzyme and cofactor are two types of non-protein compounds that aid the function of enzymes that catalyze a wide variety of biochemical reactions in living organisms. Both coenzymes and cofactors bind to the active site of the enzyme. There are two types of cofactors known as coenzymes and metals. Coenzymes are organic molecules that bind loosely to the enzyme. Metals are inorganic prosthetic groups that bind tightly to the enzyme. Coenzymes are mainly involved in the conversion of electrons, certain atoms or functional groups. However, the main difference between coenzyme and cofactor lies in the way they bind to the enzyme during catalysis of biochemical reactions.

Reference: 1. Helmenstine, Ph.D. Annemarie. "What is a coenzyme? Definition and examples. "Thought Co. Np, nd web. May 22, 2017. <https://www.thoughtco.com/definition-of-coenzyme-and-examples-604932>. 2. "Cofactor". Encyclopædia Britannica. Encyclopædia Britannica, Inc., nd Web. May 22, 2017. <https://www. britica.com/science/cofactor>. 3. “Coenzymes and Cofactors.” Coenzymes and Cofactors. Np, nd web. May 22, 2017. <http://academic.brooklyn.cuny.edu/biology/bio4fv/page/coenzy_.htm>.

Image courtesy: 1. “DHFR reaction scheme” by Bekidl - Own work (CC BY-SA 4.0) via Commons Wikimedia 2. “Enolase active site” by Kthompson08 in the English Wikipedia (Public Domain) via Commons Wikimedia

About the author: Lakna

Lakna, a graduate in molecular biology and biochemistry, is a molecular biologist and has a broad and strong interest in discovering things related to nature