Fundamentals of Biochemistry - A. A. Anisimov 1986

Enzymes
General principles of enzyme structure

Until the beginning of the 20th century, very little was known about the Chemical Nature of Enzymes, yet hypotheses regarding their proteinaceous nature had already been put forward. This viewpoint was held by Professor N. Ye. Lyaskovsky of Moscow University, and later similar opinions were expressed by Academician I. P. Pavlov, the German chemist E. Fischer, and others; however, these assumptions lacked experimental confirmation. A different perspective was held by the renowned German chemist R. Willstätter, who achieved major success in the Isolation and Purification of enzymes. Upon studying The properties of isolated enzymes, R. Willstätter concluded that they belong to a special Class of substances consisting of two components: a low-molecular-weight active moiety (the agon) and a high-molecular-weight carrier (the pheron).

During the 1920s and 1930s, accumulating evidence increasingly indicated that enzymes are Proteins. In 1926, D. Sumner (USA) isolated the enzyme urease in crystalline protein form from jack bean seeds. Somewhat later, in 1931, D. Northrop (USA) obtained crystalline Pepsin. These studies definitively proved the protein nature of enzymes. In recognition of their major contributions to enzymology, D. Sumner and D. Northrop were awarded the Nobel Prize in 1946.

The relative molecular mass of Proteins with Enzymatic Properties ranges from 15,000 to several million. Enzymatic proteins exhibit the same physicochemical properties as proteins devoid of these Functions. Enzymes are Globular proteins, and their molecules may consist of either simple or complex proteins. In the former case, enzymes are referred to as single-component, and in the latter, as two-component.

The protein moiety of two-component enzymes is called the apoenzyme, and the molecule as a whole is termed the holoenzyme. Non-protein components that readily dissociate from the complex with the enzymatic protein are conventionally called Coenzymes. They act as acceptors (or Donors) of atoms or functional groups removed from (or added to) the substrate. Consequently, it is considered more accurate to view coenzymes as co-substrates. This is clearly illustrated by the following reactions (E — enzyme, K — coenzyme, AH₂, B — substrates):

Before a new AH₂ molecule can be oxidized, the coenzyme KH₂ must return to its initial state K. This is accomplished with the participation of another enzyme E', to which the reduced coenzyme is transferred.

If the non-protein moiety of an enzyme is firmly bound to the protein and does not dissociate from it during the cycle of biochemical reactions, it is conventionally called a prosthetic group. However, there is no sharp boundary between coenzymes and prosthetic groups, and the strength of the bond between enzymatic proteins and non-protein components varies widely.

Non-protein Components of the enzyme molecule are also commonly referred to as Cofactors. The association of the protein and non-protein parts of an enzyme can be mediated by ionic bonds, Hydrogen Bonds, hydrophobic interactions, and less frequently, by covalent bonds.

The functions of coenzymes and prosthetic groups include: 1) Participation in the catalytic act, 2) establishing contact between the enzymatic protein and the substrate, and 3) stabilization of the apoenzyme. The apoenzyme, in turn, enhances the catalytic activity of the non-protein moiety and, furthermore, determines the reaction Specificity of the enzymes, given that the same chemical non-protein moiety can function as part of various enzymes. For instance, NAD⁺ serves as a coenzyme for numerous dehydrogenases — Lactate dehydrogenase (LDH), malate dehydrogenase (MDH), etc.; they differ in the apoenzyme, protein portion of the molecule.