BRENDA and the IUBMB
Nomenclature and Classification of Enzymes
The IUBMB maintains a list of enzyme classifications. This list is authorized by the Enzyme Nomenclature Committee, a group of enzymology experts. Since 1996, curation experts from the BRENDA team participate as an active part in the Enzyme Nomenclature Committee.
Definitions of some common terms used in the field of enzymology
The IUBMB provides a set of accepted definitions for some of the common terms used in the field of enzymology. Over the years, many definitions have been published for these terms. Unfortunately, these definitions have not always been in full agreement with each other, resulting in some confusion. By providing the following definitions, prepared by Ron Caspi, which are endorsed by the Enzyme Commission, the IUBMB hopes to help consolidate the use of these terms (original link).
Enzymes are macromolecular biological catalysts of biochemical reactions. Most enzymes are proteins, but a small number of catalytic RNA molecules, known as ribozymes, are also included in this definition.
Enzymes do not alter the reaction's equilibrium; they accelerate the reaction by lowering its activation energy or by facilitating an alternative catalytic mechanism. Enzymes differ from simple chemical catalysts in showing specificity for individual compounds or groups of compounds.
Generally speaking, enzymes are not consumed during the reaction they catalyse and are ready to catalyse another reaction as soon as they release the reaction's product(s). However, in a small number of cases enzymes may also participate as substrates in the reaction they catalyse (e.g. enzymes that transfer sulfur from an internal iron-sulfur cluster to a substrate), in which case the enzyme must be restored to its active state before it can catalyse an additional cycle.
- Proenzymes, apoenzymes and holoenzymes
Some enzymes are produced in an inactive form and require certain modifications before they are able to catalyse reactions. A proenzyme, also known as a zymogen, is an inactive precursor of an enzyme that must be cleaved before becoming active. The cleavage could be performed by the enzyme itself following an environmental change (e.g. in pH) or it may require a peptidase. Sometimes the term preproenzyme is used, indicating that the precursor also contains a signal peptide that directs it to a specific organelle or subcellular localization, which needs to be cleaved to produce the proenzyme. Some enzymes are only active when bound to additional non-protein molecules (see cofactors below). The inactive form of such enzymes is called an apoenzyme, while the active form is called a holoenzyme. These terms are not normally applied to the freely reversible binding of substrates or activators.
Examples for a modification from an apo form to a holo form is the attachment of a 4'-phosphopantetheine group, removed from coenzyme A, to a serine residue of the enzyme, which allows the enzyme to bind acyl moieties.
- Reactants, substrates and products
A reactant is a chemical compound that participates in, and is modified during, an enzymic reaction. Compounds that existed prior to the reaction are called substrates, and compounds that are produced during the reaction are called products. Enzymes may act on single or multiple substrates, depending on the specific reaction and enzyme. Following the chemical transformation, the product(s) is/are released from the enzyme.
Substrates are sometimes classified further into main substrates and cosubstrates. This distinction derives from the role that the compound plays during the reaction. Cosubstrates commonly provide electrons, protons, phosphate groups, methyl groups etc. for the modification of the main substrate, and most cosubstrates participate in many different reactions and are used by several different enzymes. Since the definition of a cosubstrate depends on its role in a specific reaction, the same compound may be considered a main substrate in one reaction and a cosubstrate in a different one. Examples for common cosubstrates include NADH, S-adenosyl-L-methionine, and ATP.
A cofactor is a non-protein chemical compound that is required by an enzyme for catalysis of a chemical reaction. Cofactors associate with inactive apoenzymes, resulting in formation of active holoenzymes. Although the state of a cofactor may change during the course of the reaction, it remains unchanged at the end of the catalytic cycle and thus, unlike cosubstrates, cofactors are not normally included in the reaction equation. Cofactors can be inorganic ions (e.g. Ca2+), inorganic molecules (e.g. an iron-sulfur cluster) or organic molecules (e.g. pyridoxal 5'-phosphate). In some cases a precursor of the cofactor binds, followed by in situ modification that generates the cofactor. Some cofactors may be formed by modification of existing amino acid residues within the enzyme. Some compounds may act as cofactors for a particular enzyme and a cosubstrate for a different enzyme, depending on whether they are restored to their active state at the end of the reaction.
- Prosthetic Groups (not acceptable)
Cofactors that are tightly bound to an enzyme have often been referred to as prosthetic groups. It should be noted that the degree of tightness required for this definition has not been defined, and that the same cofactor may bind differently to different enzymes, making this term imprecise. Thus, it is recommended not to use it.
The term "coenzyme" has been used in the past to refer to chemical compounds that serve functions that fit both the cosubstrate and cofactor categories. The term is currently included in the IUPAC Gold Book. It is strongly recommended to use the alternative terms cosubstrate and cofactor. For historical reasons, the term is acceptable in the case of the well-established names coenzyme A, B, M, and F420.