Cofactors vs Coenzymes- Definition, 11 Key Differences, Examples

Cofactors Definition

A cofactor is the non-protein part of an enzyme that is essential for the enzyme’s activity as a catalyst.

• Cofactors, together with the apoenzyme (protein component), form the complete enzyme (holoenzyme). The removal of the cofactor from an enzyme results in the loss of enzymatic activity.
• Cofactors can also be termed as helper molecules that assist in the biochemical transformation of different biomolecules.
• Cofactors can be metal ions, organic compounds, or other chemical substances that have properties otherwise absent in amino acids. Cofactors are either produced within the body like ATP or consumed in the diet.
• The cofactor is a broader group that contains other groups like coenzymes and prosthetic groups depending on the groups’ characteristics. 
• Cofactors can also be differentiated into organic and inorganic cofactors. Organic cofactors include organic molecules like flavin, whereas inorganic cofactors include metal ions like Mg²⁺, Cu²⁺.
• Even though in most cases, a single enzyme contains a single cofactor, there are some enzymes and enzyme complexes that require several cofactors.
• The binding of cofactors to the protein unit of the enzyme also differs in different enzymes. Some cofactors are loosely bound to the apoenzyme, whereas some are bonded by covalent bonds, which require denaturation of the enzyme.
• Cofactors can be differentiated from other similar structures like ligands in that the functions of the cofactors are derived from the binding.
• The primary function of cofactors is to supply chemical groups or elements that are not present within the protein unit but are required for the functioning of the enzyme.

Coenzymes Definition

Coenzymes are organic non-protein part of an enzyme which functions as cofactors for the function of catalysis.

• Coenzymes are a type of cofactors that perform similar functions but include freely diffusion organic compounds.
• The coenzymes usually participate in the enzyme-mediated catalysis in stoichiometric amounts like chemical substances.
• These are usually modified during the reaction and might even require a different enzyme-mediated catalyzed reaction to restore them to their original state.
• Coenzymes can further be divided into two groups; prosthetic groups and cosubstrates. Prosthetic groups remain covalently and permanently bound to the protein, whereas the cosubstrates remain transiently bound to the proteins. The function of both the type of coenzymes is the same.
• Coenzymes, unlike cofactors, are not consumed through the diet. These are produced in the body during different biochemical pathways.
• Coenzymes are often thermostable and dialyzable in nature. These may be attached directly to the protein unit of the enzyme or are present in the cytoplasm.
• Coenzymes account for about 1% of the total enzyme molecule in most enzymes.
• Most of the coenzymes are derived from vitamins like biotin and riboflavin, but some non-vitamin coenzymes like ATP and coenzyme A are also found that are produced during chemical activities in the body.

11 Major Differences (Cofactors vs Coenzymes)

Examples of Cofactors

Iron-Sulfur Clusters

• Iron-sulfur clusters are complexes composed of iron and sulfur atoms held together within the protein subunit by cysteinyl residues.
• These clusters have unique properties that are not observed in amino acids or other units within the proteins.
• Iron-sulfur complexes play structural and functional roles in electron transfer and redox sensing. The clusters have an important role in the redox reactions of the electron transport chain in mitochondria and chloroplasts.
• Both iron and sulfur atoms are capable of storing and releasing electrons with greater ease than other atoms.
• These are found in enzymes like NADH dehydrogenase, complex I, and complex II within the mitochondria.

Examples of Coenzymes

Thiamine pyrophosphate

• Thiamine pyrophosphate is a derivative of thiamine or Vitamin B1 produced by the enzyme thiamine diphosphokinase.
• It is found in all living systems and is involved in the catalysis of different biochemical reactions.
• Thiamine pyrophosphate is synthesized within the cytoplasm and is essential for the activity of enzymes like transketolase and pyruvate- and oxoglutarate-dehydrogenases.
• It is involved in biochemical pathways involved in the production of ATP, NADPH, and ribose-5-phosphate, critical for the generation of cellular energy.
• Thiamine pyrophosphate catalyzes the reversible decarboxylation of carbon compounds.
• Deficiency of Vitamin B1 is one of the causes of Korsakoff Syndrome in people with alcohol addiction.

Folic Acid

• Folic acid is a vitamin-derived coenzyme required for the production of nucleic acids and amino acids.
• Folic acid serves as a growth factor in the metabolism of one-carbon compounds like formate and formaldehyde.
• These compounds are building blocks of purines and certain pyrimidines essential for different nucleic acids.
• Enzymes involving folic acid as a coenzyme include serine hydroxymethylase, among others that are involved in nucleic acid synthesis. 

References

• Jain JL, Jain S and Jain N (2005). Fundamentals of Biochemistry. S. Chand and Company.
• Nelson DL and Cox MM. Lehninger Principles of Biochemistry. Fourth Edition. 
• Berg JM et al. (2012) Biochemistry. Seventh Edition. W. H Freeman and Company.
• Madigan MT et al. (2012). Brock Biology of Microorganisms. Thirteenth Edition. Pearson Education, Inc
• Huennekens, F. M., et al. “Folic Acid Coenzymes.” Science, vol. 128, no. 3316, 1958, pp. 120–124. JSTOR, www.jstor.org/stable/1754600. Accessed 28 Feb. 2021.
• https://pediaa.com/difference-between-coenzyme-and-cofactor/