Enzymes are either proteins (polymers of amino acids) or ribozymes (polymers of ribonucleotides). Some protein-based enzymes require small molecules called cofactors to become fully functional. The relationship between enzymes and cofactors is shown by the equation
apoenzyme + cofactor = holoenzyme
where apoenzyme refers to the nonfunctional protein and holoenzyme refers to the completely functional enzyme.
There are two types of cofactors: metal ions and small organic molecules. The latter of the two are also called coenzymes. The relationship between cofactor and coenzyme and some further subclassification can be seen in the following simple outline.
- Essential ions
- Loosely bound (metal-activated enzymes)
- Tightly bound (metalloenzymes )
- Tightly bound prosthetic groups
- Loosely bound cosubstrates
Metal-activated enzymes may have an absolute requirement for the metal ion, or they may simply have enhanced activity in the presence of the metal ion. Phosphofructokinase is an example of a metal-activated enzyme, which catalyzes the reaction
fructose-6-phosphate + ATP → fructose-1,6-bisphosphate + ADP
A divalent metal ion (Mg2+) is needed to coordinate the phosphate groups on the ATP molecule in order for phosphofructokinase to successfully catalyze this reaction. Mg2+, Mn2+, Ca2+, and K+ often function as cofactors for metal-activated enzymes.
Metalloenzymes are enzymes that have a tightly bound metal ion. These metal ions are normally incorporated into the enzymes during enzyme synthesis , and removal of the metal ions often results in the complete denaturation of the enzyme. These metal ions may contribute either to the structure or the catalytic mechanism of a metalloenzyme. For example, horse liver alcohol dehydrogenase contains two tightly bound zinc ions (Zn2+). The first zinc ion is structural: it is bound to four cysteine side chains and is essential to maintain the structural integrity of the enzyme. The second zinc ion is catalytic: it is bound to the side chains belonging to two cysteines and one histidine at the active site of the enzyme, and it participates in the catalytic cycle of the enzyme.
A wide range of metal ions is present in metalloenzymes as cofactors. Copper zinc superoxide dismutase is a metalloenzyme that uses copper and zinc to help catalyze the conversion of superoxide anion to molecular oxygen and hydrogen peroxide. Thermolysin is a protease that uses a tightly bound zinc ion to activate a water atom, which then attacks a peptide bond. Aconitase is one of the enzymes of the citric acid cycle; it contains several iron atoms bound in the form of iron-sulfur clusters, which participate directly in the isomerization of citrate to isocitrate. Other metal ions found as cofactors in metalloenzymes include molybdenum (in nitrate reductase), selenium (in glutathione peroxidase), nickel (in urease), and vanadium (in fungal chloroperoxidase).
see also Catalysis and Catalysts; Coenzymes; Denaturation; Enzymes; Krebs Cycle.
Paul A. Craig
Horton, H. Robert, et al. (2002). Principles of Biochemistry, 3rd edition. Upper Saddle River, NJ: Prentice Hall.
Nelson, David L., and Cox, Michael M. (2000). Lehninger Principles of Biochemistry, 3rd edition. New York: Worth Publishers.
Voet, Donald; Voet, Judith G.; and Pratt, Charlotte (1999). Fundamentals of Biochemistry. New York: Wiley.