Introduction to Enzymes

Enzymes are catalysts that change the rate of a reaction without being changed themselves. Enzymes are highly specific and their activity can be regulated. Virtually all enzymes are proteins, although some catalytically active RNAs have been identified. 

The active site is the region of the enzyme that binds the substrate, to form an enzyme-substrate complex, and transforms it into product. The active site is a three-dimensional entity, often a cleft or crevice on the surface of the protein, in which the substrate is bound by multiple weak interactions. Two models have been proposed to explain how an enzyme binds its substrate the lock-and-key model and the induced-fit model. 

The substrate specificity of an enzyme is determined by the properties and spatial arrangement of the amino acid residues forming the active site. The serine proteases trypsin, chymotrypsin and elastase cleave peptide bonds in protein substrates on the carboxyl side of positively charged, aromatic and small side-chain amino acid residues, respectively, due to complementary residues in their active sites. 

Enzymes are classified into six major groups on the basis of the type of reaction that they catalyze. Each enzyme has a unique four-digit classification number. 

An enzyme assay measures the conversion of substrate to product, under conditions of cofactors, pH and temperature at which the enzyme is optimally active. High substrate concentrations are used so that the initial reaction rate is proportional to the enzyme concentration. Either the rate of appearance of product or the rate of disappearance of substrate is measured, often by following the change in absorbance using a spectrophotometer. Reduced nicotinamide adenine dinucleotide (NADH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH), which absorb light at 340 nm, are often used to monitor the progress of an enzyme reaction. 

The reaction is stereospecific because each new olefin monomer always enters and reacts from the same ligand position on the titanium active site. A stereoregular polyolefin results with all substituents pointing in the same direction. It is an isotactic polymer. If the groups alternate on the chain it is a syndiotactic polymer. If the orientation is random, the molecule is said to be atactic. 

This unique example of solid surface catalysis has many analogies with an enzymatic reaction. In particular there is an active site located in a specific region of the metal surface to accommodate the substrate, and the transformation is always stereospecific. 

The outstanding characteristic of enzyme catalysis is that the enzyme specifically binds it substrate and the reactions take place in the confines of the enzyme-substrate complex. Thus, to understand how an enzyme works, we do not only need to know the structure of the native enzyme but also the structure of the complexes of the enzyme with its substrates, intermediates, and products. 

Why are enzymes macromolecules The reason is that the active center must be of a defined or highly ordered geometry if it is to contain all the binding and catalytic amino acid residues in a correct alignment for optimal catalysis. This imposes a heavy entropy demand upon the system which can be compensated for at the expense of another already ordered region of the biopolymer (58). 

Enzymes catalyze biochemical reactions stereospecifically. For this reason asymmetric syntheses are very common in nature and are often essentially unidirectional. Consequently, most natural products are optically active as 

3 Kinetics Single Substrate Multiple Substrates Metabolism of Drugs 

The catalytic action of enzymes arises from their underlying protein structure. Therefore, appreciation of enzymes first requires a working understanding of the different levels of protein structure. 

Enzymes are catalysts, and catalysts have two key qualities. First, catalysts increase the rate of a reaction. Second, catalysts are not consumed in the reaction and therefore do not appear in the overall balanced reaction equation. Catalysts appear throughout everyday life. Most simple hand tools are catalysts. For example, a shovel greatly accelerates the rate at which one can move dirt or gravel. Furthermore, the same shovel can be used day after day and work as efficiently on the last day as on the first. A shovel facilitates a process but is not consumed by the process. Moving dirt does not absolutely require a shovel, but using a shovel certainly beats using one s bare hands. 

Enzymes have all the qualities mentioned previously for an acid catalyst. Enzymes are not consumed in the overall reaction, and they accelerate both the forward and reverse reaction by altering the mechanism and/or lowering the activation energy of the key steps. Often, the product immediately reacts in a subsequent reaction, and the reverse reaction of the enzyme can be ignored. 

FIGURE 4.2 Acid catalyzed reaction coordinate for hydrolysis of 4.1 

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In addition, Chapters 6 and 7 could be reserved for the enrichment of the treatment of kinetics, and Chapter 10 can be used for an introduction to enzyme kinetics dealing with some of the problems in the reactor design chapters. 

Chapters 2 through 6 introduced many asymmetric organic reactions catalyzed by small molecules, such as C-C bond formation, reduction, and oxidation reactions. Chapter 7 provided further examples of how asymmetric reactions are used in organic synthesis. This chapter starts with a general introduction to enzyme-catalyzed asymmetric organic reactions. 

Introductions to enzyme kinetics and bioenergetics are given with explanations of key terms such as Km and Vmax coenzymes, cofactors and inhibitors typical metabolic reactions free energy exergonic and endergonic reactions, catabolism and anabolism. 

Bugg, T. (1997) An Introduction to Enzyme and CoEnzyme Chemistry, Blackwell, Oxford. 

R. Boyer, Concepts in Biochemistry (1999), Brooks/Cole (Pacific Grove, CA), pp. 142-173. An introduction to enzymes and kinetics. 

D. Voet and J. Voet, Biochemistry, 2nd ed. (1995), John Wiley Sons (New York), pp. 332-410. An introduction to enzymes. 

A Lehninger, D Nelson, and M Cox, Principles of Biochemistry, 3rd ed (1999), Worth Publishers (New York), pp 243-292 Introduction to enzymes C Matthews, K. van Holde, and K Ahem, Biochemistiy, 3rd ed (2000), Ben)amin/Cum-mings (San Francisco), pp 360-413 Introduction to enzyme kinetics L Stryer, Biochemistry, 4th ed (1995), W H Freeman (New York), pp 181-204 Introduction to enzymes and kinetics... 

There are many factors that influence the outcome of enzymatic reactions in carbon dioxide. These include enzyme activity, enzyme stability, temperature, pH, pressure, diffusional limitations of a two-phase heterogeneous mixture, solubility of enzyme and/or substrates, water content of the reaction system, and flow rate of carbon dioxide (continuous and semibatch reactions). It is important to understand the aspects that control and limit biocatalysis in carbon dioxide if one wants to improve upon the process. This chapter serves as a brief introduction to enzyme chemistry in carbon dioxide. The advantages and disadvantages of running reactions in this medium, as well as the factors that influence reactions, are all presented. Many of the reactions studied in this area are summarized in a manner that is easy to read and referenced in Table 6.1. 

An Introduction to Enzyme and Coenzyme Chemistry, T. Bugg, Blackwell Stience 1997, 247 pp., ISBN 0-86542-793-3 (paperback). This is a superb undergraduate/ postgraduate textbook about enzymes. It is well written and illustrated, with interesting examples and well-thought-out exercises. 

Introduction to enzymes (Cl) Antibodies as tools (D5) Membrane protein and carbohydrate (E2)... 

Bugg, T. D. H. 2004 Introduction to Enzyme and Coenzyme Chemistry, 2nd edn., Blackwell Publishing, Oxford UK. 

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