4.5: Cofactors and Coenzymes

Enzymes require additional components for proper function. There are two such classes of molecules: cofactors and coenzymes. Cofactors are metallic ions and coenzymes are non-protein organic molecules. Both of these types of helper molecule can be tightly bound to the enzyme or bound only when the substrate binds.

Cofactors are present in ~30% of mature proteins. They are frequently incorporated into an enzyme as it is folded and are involved in the enzyme’s catalytic activity. Magnesium is an essential cofactor for over 300 enzymes in the human body, including DNA polymerase. In this case, the magnesium ion aids in the formation of the phosphodiester bond on the DNA backbone. Iron, copper, cobalt, and manganese are other common cofactors.

Many vitamins are coenzymes, as they are nonprotein, organic helper molecules for enzymes. For example, biotin—a type of B vitamin—is important in a variety of enzymes that transfer carbon dioxide from one molecule to another. Biotin, vitamin A and other vitamins must be ingested in our diet, as they cannot be made by human cells.

In many cases, enzymes require additional molecules—called cofactors—to function. These helper molecules can either be classified as metallic ions or organic, non-protein molecules. 

For example, during the first step of glycolysis, the cofactor magnesium binds to ATP, tightening the bond between two of the phosphate groups. This action allows the last phosphate group to be more easily released by the enzyme hexokinase, transforming glucose into glucose 6-phosphate. Therefore, magnesium, as a cofactor, binds to and increases the efficiency of the ATP. 

The other subset of cofactors—coenzymes—are organic compounds, usually derivatives of vitamins.  

For instance, Vitamin C is an important coenzyme in the synthesis of the protein collagen. When a hydroxylase binds to collagen, Vitamin C facilitates the hydroxylation of residues on the collagen. With the help of Vitamin C, the hydroxylase promotes the change in the shape of the collagen to its final triple helical structure, which is essential to the maintenance of important body tissues.