Comparatively Speaking: Cofactors vs. Coenzymes

February 23, 2010 | Contact Author | By: Anthony J. O'Lenick, Jr., Siltech LLC
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Editor's note: Enzymes for DNA repair or Coenzyme Q10 for antioxidant and antiaging benefits have become typical ingredients in today's skin care. Here, industry expert O'Lenick illustrates the difference between cofactors and coenzymes.

While some enzymes do not need additional components to show full activity, others require non-protein molecules known as cofactors to be bound for activity. Cofactors can either be inorganic, such as metal ions and iron-sulfur clusters, or organic compounds, such as flavin and heme. Organic cofactors can either be prosthetic groups, which are tightly bound to an enzyme, or coenzymes, which are released from the enzyme's active site during the reaction. Coenzymes include the reduced form of nicotinamide adenine dinucleotide (NADH), the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) and adenosine triphosphate. These molecules transfer chemical groups between enzymes.1

An example of an enzyme that contains a cofactor is carbonic anhydrase, which has a zinc cofactor bound as part of its active site.2 These tightly bound molecules are usually found in the active site and are involved in catalysis. For example, flavin and heme cofactors are often involved in redox reactions.

Enzymes that require a cofactor but do not have one bound are called apoenzymes or apoproteins. An apoenzyme with its cofactor(s) is called a holoenzyme, which is the active form. Most cofactors are not covalently attached to an enzyme but are tightly bound. However, organic prosthetic groups can be covalently bound such as thiamine pyrophosphate in the enzyme pyruvate dehydrogenase. The term holoenzyme can also be applied to enzymes that contain multiple protein subunits, such as the DNA polymerases. Here, we refer to the holoenzyme as a complete complex containing all the subunits needed for activity.

Coenzymes are small organic molecules that transport chemical groups from one enzyme to another. Some of these chemicals, such as riboflavin, thiamine and folic acid, are vitamins. These vitamins are compounds that cannot be synthesized by the body and must be acquired from the diet. The chemical groups carried include: the hydride ion (H-), carried by nicotinamide adenine dinucleotide (NAD+), or nicotinamide adenine dinucleotide phosphate (NADP+); the acetyl group, carried by coenzyme A; formyl, methenyl or methyl groups, carried by folic acid; and the methyl group, carried by S-adenosylmethionine.3

Since coenzymes are chemically changed as a consequence of enzyme action, it is useful to consider coenzymes to be a special class of substrates, or second substrates, which are common to many different enzymes.

Coenzymes are usually regenerated and their concentrations are maintained at a steady level inside the cell. For example, NADPH is regenerated through the pentose phosphate pathway and S-adenosylmethionine is regenerated through methionine adenosyltransfera. Coenzymes are involved in the transfer of hydrogen ions and electrons.

1. MWG de Bolster, Glossary of terms used in bioinorganic chemistry: Coenzyme, international union of pure and applied chemistry (1997)
2. Z Fisher et al, Structural and kinetic characterization of active-site histidine as a proton shuttle in catalysis by human carbonic anhydrase II, Biochemistry 44 (4) 1097–115 (2005)
3. AL Wagner, Vitamins and Coenzymes, Krieger Publishing Co. (1975)