8885dc06190-2371/27/047:13 AM Page190 chapter ENZYMES 6.1 An Introduction to Enzymes 191 H2O in the presence of oxygen is a highly exergonic 6.2 How Enzymes Work 193 process, releasing free energy that we can use to think, move, taste, and see. However, a bag of sugar can re- 6.3 Enzyme Kinetics as an Approach to Understanding main on the shelf for years without any obvious con Mechanism 202 version to CO2 and H.O. Although this chemical process 6.4 Examples of Enzymatic Reactions 213 is thermodynamically favorable, it is very slow! Yet when 6.5 Regulatory Enzymes 225 sucrose is consumed by a human (or almost any other organism), it releases its chemical energy in seconds The difference is catalysis. Without catalysis, chemical reactions such as sucrose oxidation could not occur on One way in which this condition might be fulfilled would a useful time scale and thus could not sustain life be if the molecules when combined with the enzyme, lay In this chapter, then, we turn our attention to the slightly further apart than their equilibrium distance when reaction catalysts of biological systems: the enzymes, [covalently joined], but nearer than their equilibrium distance when free.... Using fischers lock and ke Enzymes have extraordinary catalytic power, often far greater than that of synthetic or inorganic catalysts simile, the key does not fit the lock quite perfectly but They have a high degree of specificity for their sub- exercises a certain strain on it strates, they accelerate chemical reactions tremen- . B S Haldane, Enzymes, 1930 dously, and they function in aqueous solutions under very mild conditions of temperature and pH Few non- Catalysis can be described formally in terms of a biological catalysts have all these properties stabilization of the transition state through tight binding to Enzymes are central to every biochemical process. Acting in organized sequences, they catalyze the the catalyst. hundreds of stepwise reactions that degrade nutrient William P Jencks, article in Advances in Enzymology, 1975 molecules, conserve and transform chemical energy, and make biological macromolecules from simple pre cursors. Through the action of regulatory enzymes metabolic pathways are highly coordinated to yield a here are two fundamental conditions for life. First, harmonious interplay among the many activities ne the living entity must be able to self-replicate(a top essary to sustain life onsidered in Part ID; second, the organism must be The study of enzymes has immense practical im- able to catalyze chemical reactions efficiently and se portance. In some diseases, especially inheritable ge- lectively. The central importance of catalysis may sur- netic disorders, there may be a deficiency or even a prise some beginning students of biochemistry, but it is total absence of one or more enzymes. For other dis easy to demonstrate. As described in Chapter 1, living ease conditions, excessive activity of an enzyme may be ystems make use of energy from the environment he cause. Measurements of the activities of enzymes in Many of us, for example, consume substantial amounts blood plasma, erythrocytes, or tissue samples are im- of sucrose---common table sugar-as a kind of fuel, portant in diagnosing certain illnesses. Many drugs ex- whether in the form of sweetened foods and drinks or ert their biological effects through interactions with as sugar itself. The conversion of sucrose to COe and enzymes. And enzymes are important practical tools,chapter T here are two fundamental conditions for life. First, the living entity must be able to self-replicate (a topic considered in Part III); second, the organism must be able to catalyze chemical reactions efficiently and se￾lectively. The central importance of catalysis may sur￾prise some beginning students of biochemistry, but it is easy to demonstrate. As described in Chapter 1, living systems make use of energy from the environment. Many of us, for example, consume substantial amounts of sucrose—common table sugar—as a kind of fuel, whether in the form of sweetened foods and drinks or as sugar itself. The conversion of sucrose to CO2 and H2O in the presence of oxygen is a highly exergonic process, releasing free energy that we can use to think, move, taste, and see. However, a bag of sugar can re￾main on the shelf for years without any obvious con￾version to CO2 and H2O. Although this chemical process is thermodynamically favorable, it is very slow! Yet when sucrose is consumed by a human (or almost any other organism), it releases its chemical energy in seconds. The difference is catalysis. Without catalysis, chemical reactions such as sucrose oxidation could not occur on a useful time scale, and thus could not sustain life. In this chapter, then, we turn our attention to the reaction catalysts of biological systems: the enzymes, the most remarkable and highly specialized proteins. Enzymes have extraordinary catalytic power, often far greater than that of synthetic or inorganic catalysts. They have a high degree of specificity for their sub￾strates, they accelerate chemical reactions tremen￾dously, and they function in aqueous solutions under very mild conditions of temperature and pH. Few non￾biological catalysts have all these properties. Enzymes are central to every biochemical process. Acting in organized sequences, they catalyze the hundreds of stepwise reactions that degrade nutrient molecules, conserve and transform chemical energy, and make biological macromolecules from simple pre￾cursors. Through the action of regulatory enzymes, metabolic pathways are highly coordinated to yield a harmonious interplay among the many activities nec￾essary to sustain life. The study of enzymes has immense practical im￾portance. In some diseases, especially inheritable ge￾netic disorders, there may be a deficiency or even a total absence of one or more enzymes. For other dis￾ease conditions, excessive activity of an enzyme may be the cause. Measurements of the activities of enzymes in blood plasma, erythrocytes, or tissue samples are im￾portant in diagnosing certain illnesses. Many drugs ex￾ert their biological effects through interactions with enzymes. And enzymes are important practical tools, ENZYMES 6.1 An Introduction to Enzymes 191 6.2 How Enzymes Work 193 6.3 Enzyme Kinetics as an Approach to Understanding Mechanism 202 6.4 Examples of Enzymatic Reactions 213 6.5 Regulatory Enzymes 225 One way in which this condition might be fulfilled would be if the molecules when combined with the enzyme, lay slightly further apart than their equilibrium distance when [covalently joined], but nearer than their equilibrium distance when free. . . . Using Fischer’s lock and key simile, the key does not fit the lock quite perfectly but exercises a certain strain on it. —J. B. S. Haldane, Enzymes, 1930 Catalysis can be described formally in terms of a stabilization of the transition state through tight binding to the catalyst. —William P. Jencks, article in Advances in Enzymology, 1975 6 190 8885d_c06_190-237 1/27/04 7:13 AM Page 190 mac76 mac76:385_reb: