Chapter 6 Basic Concepts of Enzyme Action

Catalytically binding. What is the role of bonding energy in enzyme catalysis?

Binding energy is maximized when an enzyme interacts with the transition state, thereby facilitating the formation of the transition state and enhancing the rate of the reaction.

Mutual attraction. What is meant by the term binding energy?

Binding energy is the fee energy released when two molecules bind together, such as when an enzyme and a substrate interact.

Induced fit

Change in enzyme structure

Protection. Suggest why the enzyme lysozyme, which degrades cell walls of some bacteria, is present in tears.

Lysozyme helps protect the fluid that surrounds eyes from bacterial infection.

Potential donors and acceptors. The hormone progesterone contains two ketone groups. At pH 7, which side chains of a protein might form hydrogen bonds with progesterone?

Potential hydrogen-bonds donors at pH7 are the side chains of the following residues: arginine, asparagine, glutamine, histidine, lysine, serine, threonine, tryptophan, and tyrosine

Mountain climbing. Proteins are thermodynamically unstable. The delta G of the hydrolysis of proteins is quite negative, yet proteins can be quite stable. Explain this apparent paradox. What does it tell you about protein synthesis?

Protein hydrolysis has a large activation energy. Protein synthesis must require energy to proceed.

What are the two properties of enzymes that make them especially useful catalysts?

Rate enhancement Substrate specificity

Substrate

Reactant in an enzyme catalyzed reaction

Active site

Site on the enzyme where catalysis takes place

Coenzymes

Small vitamin-derived organic cofactors

Shared properties. What are the general characteristics of enzyme active sites?

The active site is a three-dimensional crevice or cleft; it makes up only a small part of the total volume of the enzyme. Active sites have unique microenvironments. A substrate binds to the active site with multiple weak interactions. The specificity of the active site depends on the active site's precise three-dimensional structure.

Stability matters. Transition-state analogs, which can be used as enzyme inhibitors and to generate catalytic antibodies, are often difficult to synthesize. Suggest a reason.

Transition states are very unstable. Consequently, molecules that resemble transition states are themselves likely to be unstable and hence, difficult to synthesize.

One a day. Why are vitamins necessary for good health?

Vitamins are converted into enzymes

Sticky situation. What would be the result of an enzyme having a greater binding energy for the substrate that for the transition state?

There would be no catalytic activity. If the enzyme-substrate complex is more stable than the enzyme-transition-state complex, the transition state would not form and catalysis would not take place.

Enzyme

protein catalyst

Cofactor

A coenzyme or metal

Partners. What does an apoenzyme require to become a holoenzyme?

A cofactor

Different partners. What are the two main types of cofactors?

Coenzymes and Metals

Apoenzyme

Enzyme minus its cofactor

Holoenzyme

Enzyme plus cofactor

A function of state. What is the fundamental mechanism by which enzymes enhance the rate of chemical reactions?

Enzymes facilitate the formation of the transition state.

Delta G0'

Function of Keq

Give with one hand, take with the other. Why does the activation energy of a reaction not appear in the final delta G of the reaction?

The energy required to reach the transition state (the activation energy) is returned when the transition state proceeds to product.

Nooks and crannies. What is the structural basis for enzyme specificity?

The intricate three-dimensional structure of proteins allows the construction of active sites that will recognize only specific substrates.

Transition state

The least-stable reaction intermediate

A tenacious mutant. Suppose that a mutant enzyme binds a substrate 100 times as tightly as does the native enzyme. What is the effect of this mutation on catalytic rate if the binding of the transition state is unaffected?

The mutation slows the reaction by a factor of 100 because the activation free energy is increased by 53.22 kJmol-1. Strong binding of the substrate relative to the transition state slows catalysis.