The nature of enzymes

All enzymes are proteins although many are conjugated proteins and are associated with non-protein groups. Their catalytic activity depends on the maintenance of their native structure and slight variations may result in significant changes in this activity. 

A common feature of enzymes is the presence of a cleft or depression in the structure which is lined with mainly hydrophobic amino acid residues and into which the substrate fits. Certain amino acid residues which are concerned with either the orientation of the substrate, and hence the specificity of the enzyme, or are involved in the catalysis of the reaction, are located in this cleft. Those amino acid residues that are associated with the latter role form the active site of the enzyme and are often located towards the base of this cleft. In most cases they are ionic or reactive and include histidine, lysine, cysteine 

Experimental studies on the effect of substrate concentration on the activity of an enzyme show consistent results. At low concentrations of substrate the rate of reaction increases as the concentration increases. At higher concentrations the rate begins to level out and eventually becomes almost constant, regardless of any further increase in substrate concentration. The choice of substrate concentration is an important consideration in the design of enzyme assays and an understanding of the kinetics of enzyme-catalysed reactions is needed in order to develop valid methods. 

The law of mass action states that the rate of a chemical reaction is proportional to the product of the concentrations of the reactants. This means that the rate of a reaction which has a single component will increase in direct relation to the increasing concentration but for a two-component reaction it will increase in proportion to the square of the concentration. These relationships 

The concept of an enzyme-substrate complex is fundamental to the appreciation of enzyme reactions and was initially developed in 1913 by Michaelis and Menten, who derived an equation that is crucial to enzyme studies. Subsequent to Michaelis and Menten several other workers approached the problem from different viewpoints and although their work is particularly useful in advanced kinetic and mechanistic studies, they confirmed the basic concepts of Michaelis and Menten. 

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Enzymes may be described a organic catalysts of biological origin. The majority are obtained from the interior of cells, but some are obtained from natural secretions such as the digestive juices and milk. For a full discussion of the nature of enzymes and the mechanism of their reactions the student should consult a work such as Chemistry and Methods of Enzymes, by J. B. Sumner and G. F. Somers (Academic Press, New York), or Enzymes, by M. Dixon and E. C. Webb[(Longman Group Ltd.). The following points should however be noted ... 

This section deals with the nature of enzymes and their importance in metabolic control is discussed more fully in Chapter 3. Enzymes are biocatalysts whose key characteristics are as follows ... 

S. Subramanian, J. B. A. Ross, L. Brand, and P. D. Ross, Investigation of the nature of enzyme-coenzyme interactions in binary and ternary complexes of liver alcohol dehydrogenase with coenzymes, coenzyme analogs, and substrate analogs by ultraviolet absorption and phosphorescence spectroscopy, Biochemistry 20, 4086-4093 (1981). 

Chapters 17 through 21 deal with carbohydrate-enzyme systems. Hehre presents some new ideas on the action of amylases. Kabat presents some new immunochemical studies on the carbohydrate moiety of certain water-soluble blood-group substances and their precursor antigens. Hassid reviews the role of sugar phosphates in the biosynthesis of complex saccharides. Pazur and co-workers present information obtained by isotopic techniques on the nature of enzyme-substrate complexes in the hydrolysis of polysaccharides. Gabriel presents a common mechanism for the production of 6-deoxyhexoses. An intermediate nucleoside-5 -(6-deoxyhexose-4-ulose pyrophosphate) is formed in each of the syntheses. 

The first reported attempts of what was then called "absolute or total asymmetric synthesis" with chiral solid catalysts used nature (naturally ) both as a model and as a challenge. Hypotheses of the origin of chirality on earth and early ideas on the nature of enzymes strongly influenced this period [15]. Two directions were tried First, chiral solids such as quartz and natural fibres were used as supports for metallic catalysts and second, existing heterogeneous catalysts were modified by the addition of naturally occuring chiral molecules. Both approaches were successful and even if the optical yields were, with few exceptions, very low or not even determined quantitatively the basic feasibility of heterogeneous enantioselective catalysis was established. 

A quarter of a century has passed since the first contribution on catalase to The Enzymes Enzyme substrate compounds Mechanism of action of hydroperoxidases (I). In this perspective, we can identify a sequence of steps in the development of ideas on the mechanism of enzymic action and the nature of enzyme-substrate compounds. The identification of these compounds and the approach to enzymic reactions at concentrations stoichiometric with the substrate caused a principal transition of viewpoint on hemoprotein catalysis from free radical mechanisms (2) unrelated to an active center toward the acceptance of catalysis occurring at the iron atom of the porphyrin (S-5). The latter concept followed natu-... 

Kollman, P. A. Kuhn, B. Perakyla, M. Computational stndies of enzyme-catalyzed reactions Where are we in predicting mechanisms and in nnderstanding the nature of enzyme catalysis , J. Phys. Chem. B 2002,106, 1537-1542. 

A major addition to the second edition is Chapter 9, which discusses computational enzymology. This chapter extends the coverage of quantum chemistry to a sister of organic chemistry—biochemistry. Since computational biochemistry truly deserves its own entire book, this chapter presents a flavor of how computational quantum chemical techniques can be applied to biochemical systems. This chapter presents a few examples of how QM/MM has been applied to understand the nature of enzyme catalysis. This chapter concludes with a discussion of de novo design of enzymes, which is a research area that is just becoming feasible, and one that will surely continue to develop and excite a broad range of chemists for years to come. 

The study of catalytic and inhibitory effects in solutions of flexible chain polymers and micelles is of sufficient intrinsic interest, so that no special justification should be required for investigations of this tyj)e. Nevertheless, many of the workers active in this field insist on emphasizing the utility of such systems as enzyme models and we should, therefore, try to answer two crucial questions. What has been learned so far from these studies about the nature of enzymic catalysis What is the probability that studies of this type will contribute to the clarification of the enzyme problem in the future ... 

Kollman, P.A., et al. (2001). Elucidating the nature of enzyme catalysis utilizing a new twist on an old methodology quantum mechanical-free energy calculations on chemical reactions in enzymes and in aqueous solution. Acc. Chem. Res. 34, 72-79... 

The nature of enzyme inhibition by profenofos and PRO was further studied in the GO-fold resistant strain and enzyme, examining enzyme kinetic activity toward 12.5, 25, 50, 100 and 200 mmol L concentrations of I-naphthyl acetate. 

V. M. Bayliss, " The Nature of Enzyme Action, London, igrg. 

Kollman PA, Kuhn B, Perakyla M. Computational studies of enzyme-catalyzed reactions where are we in predicting mechanisms and in understanding the nature of enzyme catalysis J Phys Chem B 2002 106 1537-1542. 

What does a graph of enzyme activity versus substrate concentration tell us about the nature of enzyme-catalyzed reactions ... 

In 1942 the application of the rate theory to biochemical systems was initiated by an examination of bacterial luminescence (with J. L. Magee) and the nature of enzyme inhibitions in bacterial luminescence (with F. H. Johnson and R. W. Williams). The collaboration with Johnson yielded a successful interpretation of the influence of temperature and pressure on bioluminescent systems and ultimately the major contribution to biological science, Kinetic Basis of Molecular Biology by Eyring with F. H. Johnson and M. J. Polissar. 

Herriott, R. M. (1983). John H. Northrop The Nature of Enzymes and Bacteriophage. Trends in Biochemical Sciences. 13 296-297. 

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