Enzymes, the

Catalysts of Life

Chapter 6

Becker’s The World of Cell

Activation Energy and the

Metastable State

While thermodynamics allows us to assess

the feasibility of a reaction, it says nothing

about the likelihood that the reaction will

actually occur at a reasonable rate in the

cell.

For a given chemical reaction to occur in

the cell, substrates must reach the

transition state, which has a higher free

energy than either the substrates or

products. Reaching the transition state

requires the input of activation energy.

Activation Energy and the

Metastable State

Because of this activation energy barrier,

most biological compounds exist in an

unreactive, metastable state. To ensure

that the activation energy requirement is

met and the transition state is achieved, a

catalyst is required, which is always an

enzyme in biological systems.

Activation Energy and the

Metastable State

Enzymes as Biological Catalysts

Catalysts, whether inorganic or organic,

act by forming transient complexes with

substrate molecules that lower the

activation energy barrier and rapidly

increase the rate of the particular

reaction.

Chemical reactions in cells are catalyzed

by enzymes, which in some cases require

organic or inorganic cofactors for activity.

The vast majority of enzymes are proteins,

but a few are composed of RNA and are

known as ribozymes.

Enzymes as Biological Catalysts

Enzymes are exquisitely specific, either for

a single specific substrate or for a class of

closely related compounds. This is

because the actual catalytic process

takes place at the active site—a pocket

or groove on the enzyme surface that

only the correct substrates will fit into.

Enzymes as Biological Catalysts

Binding of the appropriate substrate at the active site causes a change in the shape of the enzyme and substrate known as induced fit. This facilitates substrate activation, often by distorting one or more bonds in the substrate, by bringing necessary amino acid side chains into the active site, or by transferring protons and/or electrons between the enzyme and substrate.

Enzymes as Biological Catalysts

Enzyme Kinetics

■ An enzyme-catalyzed reaction

proceeds via an enzyme substrate

intermediate. Most reactions follow

Michaelis–Menten kinetics, characterized

by a hyperbolic relationship between the

initial reaction velocity v and the substrate

concentration [S].

■ The upper limit on velocity is called Vmax,

and the substrate concentration needed to

reach one-half of this maximum velocity is

termed the Michaelis constant, Km. The

hyperbolic relationship between v and [S]

can be linearized by a double-reciprocal

equation and plot, from which Vmax and

Km can be determined graphically.

Enzyme Kinetics

■ Enzyme activity is sensitive to

temperature, pH, and the ionic

environment. Enzyme activity is also

influenced by substrate availability,

products, alternative substrates, substrate

analogues, drugs, and toxins, most of which

have an inhibitory effect.

Enzyme Kinetics

■ Irreversible inhibition involves covalent

bonding of the inhibitor to the enzyme

surface, permanently disabling the enzyme.

A reversible inhibitor, on the other hand,

binds noncovalently to an enzyme in a

reversible manner, either at the active site

(competitive inhibition) or elsewhere on the

enzyme surface (noncompetitive inhibition).

Enzyme Kinetics

Enzyme Regulation

■ Enzymes must be regulated to adjust their

activity levels to cellular needs. Substrate-

level regulation involves the effects of

substrate and product concentrations on

the reaction rate. Additional control

mechanisms include allosteric regulation

and covalent modification.