Cofactor (biochemistry)

The bound heme cofactor of succinate dehydrogenase, an enzyme in the mitochondrial electron transfer chain. The large semi-transparent sphere indicates the location of the iron ion.

A cofactor is a non-protein chemical compound that is bound (either tightly or loosely) to an enzyme and is required for catalysis.^[1] They can be considered "helper molecules/ions" that assist in biochemical transformations. Certain substances such as water and various abundant ions may be bound tightly by enzymes, but are not considered to be cofactors since they are ubiquitous and rarely limiting. Some sources limit the use of the term "cofactor" to inorganic substances.^[2][3]

Cofactors can be divided into two broad groups: coenzymes and prosthetic groups. Coenzymes are small organic non-protein molecules that carry chemical groups between enzymes. These molecules are not bound tightly by enzymes and are released as a normal part of the catalytic cycle. In contrast, prosthetic groups form a permanent part of the protein structure.

Apoenzymes and holoenzymes

An enzyme without a cofactor is referred to as an apoenzyme, and the completely active enzyme (in addition to the cofactor) is called a holoenzyme.

Apoenzyme + cofactor <=> Holoenzyme

Metal ion cofactors

Further information: Metalloproteins

Metal ions are common cofactors. The study of these cofactors falls under the area of bioinorganic chemistry. In nutrition, the list of essential trace elements reflects their role as cofactors. In humans this list commonly includes iron, manganese, cobalt, copper, zinc, selenium, and molybdenum.^[4] Although chromium deficiency causes impaired glucose tolerance, no human enzyme that uses this metal as a cofactor has been identified.^[5][6] Iodine is also an essential trace element, but this element is used as part of the structure of thyroid hormones rather than as an enzyme cofactor.^[7] Calcium is another special case, in that it is required as a component of the human diet, and it is needed for the full activity of many enzymes: such as nitric oxide synthase, protein phosphatases or adenylate kinase, but calcium activates these enzymes in allosteric regulation, often binding to these enzymes in a complex with calmodulin.^[8] Calcium is therefore a cell signaling molecule, and not usually considered as a cofactor of the enzymes it regulates.^[9]

Other organisms require additional metals as enzyme cofactors, such as vanadium in the nitrogenase of the nitrogen-fixing bacteria of the genus Azotobacter,^[10] tungsten in the aldehyde ferredoxin oxidoreductase of the thermophilic archaean Pyrococcus furiosus,^[11] and even cadmium in the carbonic anhydrase from the marine diatom Thalassiosira weissflogii.^[12][13]

In many cases, the cofactor includes both an inorganic and organic component. One diverse set of examples are the haem proteins, which consists of a porphyrin ring coordinated to iron.

Cofactors and coenzymes

Cofactors vary in their location and the tightness of their binding to the host enzyme. When bound tightly to the enzyme, cofactors are called prosthetic groups. Loosely-bound cofactors typically associate in a similar fashion to enzyme substrates. These are better described as coenzymes, which are organic substances that directly participate as substrates in an enzyme reaction. Vitamins can serve as precursors to coenzymes (e.g. vitamins B₁, B₂, B₆, B₁₂, niacin, folic acid) or as coenzymes themselves (e.g. vitamin C).

Non-enzymatic cofactors

The term is used in other areas of biology to refer more broadly to non-protein (or even protein) molecules that either activate or inhibit proteins. For example, ligands such as hormones that bind to and activate receptor proteins are termed cofactors or coactivators, while molecules that inhibit receptor proteins are termed corepressors.

See also

• Enzyme catalysis
• Inorganic chemistry

References

External links

• Cofactor at eMedicine Dictionary
• MeSH Enzyme+cofactors