Structural Biochemistry/Enzyme/Apoenzyme and Holoenzyme

Cofactor: A Definition

Many enzymes require an additional small molecule, known as a cofactor to aid with catalytic activity. A cofactor is a non-protein molecule that carries out chemical reactions that cannot be performed by the standard 20 amino acids. Cofactors can be either inorganic molecules (metals) or small organic molecules (coenzymes).

Cofactors, mostly metal ions or coenzyme, are inorganic and organic chemicals that function in reactions of enzymes. Coenzymes are organic molecules that are nonproteins and mostly derivatives of vitamins soluble in water by phosphorylation; they bind apoenzyme protein molecule to produce active holoenzyme.

Figure 1-1: A flow chart of the two types of cofactors.

Apoenzyme- An enzyme that requires a cofactor but does not have one bound. An apoenzyme is an inactive enzyme, activation of the enzyme occurs upon binding of an organic or inorganic cofactor.

Holoenzyme- An apoenzyme together with its cofactor. A holoenzyme is complete and catalytically active. Most cofactors are not covalently bound but instead are tightly bound. However, organic prosthetic groups such as an iron ion or a vitamin can be covalently bound. Examples of holoenzymes include DNA polymerase and RNA polymerase which contain multiple protein subunits. The complete complexes contain all the subunits necessary for activity.

Figure 1-2: Illustrates that an Apoenzyme + Cofactor = Holoenzyme.

Examples of Holoenzymes

DNA polymerase is a holoenzyme that catalyzes the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerase is an active participant in DNA replication. It reads the intact DNA strand as a template and uses it to synthesize the new strand. The newly polymerized DNA strand is complementary to the template strand and identical to template's original partner strand. DNA polymerase uses a magnesium ion for catalytic activity.

Figure 1-3: Illustrates the holoenzyme DNA polymerase a multi-subunit complex.

RNA polymerase is also a holoenzyme that catalyzes RNA. RNA polymerase is needed for constructing RNA chains from DNA genes as templates, a process known as transcription. It polymerizes ribonucleotides at the 3' end of an RNA transcript.

Figure 1-4: Illustrates the holoenzyme RNA polymerase a subunit complex.

References

Berg, Jeremy M., et al. "Biochemistry". 6th ed. W.H. Freeman and Company, NY, 2006.