Enzyme covalent catalysis

Covalent enzyme catalysis involves the formation of a transient covalent bond between an enzyme and its substrate. Below are the general structures of commonly encountered so-called acyl-enzyme intermediates and other covalent derivatives. 

Elucidating Mechanisms for the Inhibition of Enzyme Catalysis An inhibitor interacts with an enzyme in a manner that decreases the enzyme s catalytic efficiency. Examples of inhibitors include some drugs and poisons. Irreversible inhibitors covalently bind to the enzyme s active site, producing a permanent loss in catalytic efficiency even when the inhibitor s concentration is decreased. Reversible inhibitors form noncovalent complexes with the enzyme, thereby causing a temporary de-... 

Because mechanism-based inactivation depends on enzyme catalysis, there cannot be more than one molecule of inactivator bound to the enzyme active site. Thus formation of the covalent E-A species cannot result in a stoichiometry of inactivator to enzyme of greater than 1 1. In the case of multimeric enzymes, however, it may not be necessary to covalently modify all of the enzyme active sites within the multi-mer in order to effect total inactivation of the enzyme. In this situation one may observe a stoichiometry of less that 1 1. Under no circumstances, however, can a mechanism-based inactivator display a stoichiometry of greater than 1 1 with the enzyme. 

Enzymes are often considered to function by general acid-base catalysis or by covalent catalysis, but these considerations alone cannot account for the high efficiency of enzymes. Proximity and orientation effects may be partially responsible for the discrepancy, but even the inclusion of these effects does not resolve the disparity between observed and theoretically predicted rates. These and other aspects of the theories of enzyme catalysis are treated in the monographs by Jencks (33) and Bender (34). 

For enzyme catalysis to occur the biocatalyst must be complementary to the reaction transition state so that weak non-covalent interactions can be formed in the ES complex. These interactions maximize when the substrate reaches the transition state. The binding energy released in the interactions (Figure 3) partially compensates the energy required to reach the top of the... 

The factors — or at least some of them — which control reactivity in intramolecular reactions are relevant to enzyme catalysis, which also involves reactions between functional groups brought together in close and precisely defined proximity (Kirby, 1980). This has been an area of lively discussion in the recent literature [for a brief summary and leading references see Paquette et al. (1990)]. The main difficulty in making generalizations about the dependence of reactivity on geometry based on results from systems in which proximity is covalently enforced lies in the constraints imposed by particular systems. These may well affect reactivity... 

Many of the basic elements of enzyme catalysis have been illustrated here, including binding of substrate, multifunctional catalysis, microenvironmental effects, covalent catalysis, and strain effects. The most remarkable rate enhancements reported to date are those brought about by apolar derivatives of PEI, a polycation. These rate enhancements are very en-... 

Proton transfers are particularly common. This acid-base catalysis by enzymes is much more effective than the exchange of protons between acids and bases in solution. In many cases, chemical groups are temporarily bound covalently to the amino acid residues of the enzyme or to coenzymes during the catalytic cycle. This effect is referred to as covalent catalysis (see the transaminases, for example p. 178). The principles of enzyme catalysis sketched out here are discussed in greater detail on p. 100 using the example of lactate dehydrogenase. 

Although most enzyme exchange studies have been investigated at equilibrium, the back exchange of labeled product while the reaction is proceeding in the forward direction can provide valuable information about enzymic catalysis. Under favorable conditions, one may utilize such isotope exchange data to learn about the order of product release and the presence of covalent enzyme-substrate compounds. One of the first systems to be characterized in this way was glucose-6-phos-phatase . ... 

Product inhibition and substrate inhibition are effects also known in enzyme catalysis that can reduce catalytic efficiency. Generally, catalytic systems (natural or artificial) based on covalent interactions are more sensitive towards inhibitions than non-covalent systems utilizing weak interactions Garcia-Junceda, E. (2008) Multi-Step Enzyme Catalysis, Wiley-VCH Verlag GmbH, Weinheim, Germany. 

Other mechanisms The active site can provide catalytic groups that enhance the probability that the transition state is formed. In some enzymes, these groups can participate in general acid-base catalysis in which amino acid residues provide or accept protons. In other enzymes, catalysis may involve the transient formation of a covalent enzyme-substrate complex. 

Escherichia coli have also developed an elegant method to control enzyme catalysis that occurs by covalent modification of each subunit. In this latter reaction a single tyrosyl residue per subunit is adenylylated to produce a stable 5 -adenylyl-O-tyrosyl derivative. Recent NMR and fluorescence data will be reviewed concerning the nature of this adenylyl site and its spatial relationship to the metal ions at the catalytic site. The enzymes responsible for the covalent adenylylation reaction comprise a cascade system for amplifying the activation or inactivation of glutamine synthetase molecules (81). 

L. E. Scriven Yes, and not only for covalent bonding but also for molecular conformation and, I believe, for structured aggregates of molecules. I would say not just enzyme catalysis in the biochemical setting, but also in its... 

It is well known from structural and kinetic studies that enzymes have well-defined binding sites for their substrates (3), sometimes form covalent intermediates, and generally involve acidic, basic and nucleophilic groups. Many of the concepts in catalysis are based on transition state (TS) theory. The first quantitative formulation of that theory was extensively used in the work of H. Eyring (4, 5 ). Noteworthy contributions to the basic theory were made by others (see (6) for review). As an elementary introduction, we will apply the fundamental assumptions of the TS theory in simple enzyme catalysis as follows. 

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