Page 99 - Color Atlas of Biochemistry

P. 99

90 Metabolism

Enzyme catalysis that productive A–B complexes will arise. In
addition, binding of the substrates results in
Enzymes are extremely effective catalysts. removal of their hydration shells. As a result
They can increase therateofa catalyzed re- of the exclusion of water, very different con-
action by a factor of 10 12 or more. To grasp the ditions apply in the active center of the en-
mechanisms involved in enzyme catalysis, we zyme during catalysis than in solution (3–5).
can start by looking at the course of an un- A third important factor is the stabilization of
catalyzed reaction more closely. the transition state as a result of interactions
between the amino acid residues of the pro-
tein and the substrate (4). This further re-
A. Uncatalyzed reaction
duces the activation energy needed to create
The reaction A + B C + Disusedasan the transition state. Many enzymes also take
example. In solution, reactants A and B are up groups from the substrates or transfer
surrounded by a shell of water molecules them to the substrates during catalysis.
(the hydration shell), and they move in ran- Proton transfers are particularly common.
dom directions due to thermal agitation. They This acid–base catalysis by enzymes is much
can only react with each other if they collide more effective than the exchange of protons
in a favorable orientation. This is not very between acids and bases in solution. In many
probable, and therefore only occurs rarely. cases, chemical groups are temporarily bound
Before conversion into the products C + D, covalently to the amino acid residues of the
the collision complex A-B hasto passthrough enzyme or to coenzymes during the catalytic
a transition state, the formation of which usu- cycle. This effect is referred to as covalent
ally requires a large amount of activation catalysis (see the transaminases, for example;
energy, E a (see p. 22). Since only a few A–B p.178). The principles of enzyme catalysis
complexescan producethisamountof en- sketched out here are discussed in greater
ergy, a productive transition state arises detail on p.100 using the example of lactate
even less often than a collision complex. In dehydrogenase.
solution, a large proportion of the activation
energy is required for the removal of the hy-
dration shells between A and B. However, C. Principles of enzyme catalysis
charge displacements and other chemical Although it is dif cult to provide quantitative
processes within the reactants also play a estimates of the contributions made by indi-
role. As a result of these limitations, conver- vidual catalytic effects, it is now thought that
sion only happens occasionally in the absence the enzyme’s stabilization of the transition
of a catalyst, and the reaction rate v is low, state is the most important factor. It is not
even when the reaction is thermodynamically tight binding of the substrate that is impor-
possible—i. e., when ∆G<0 (see p.18). tant, therefore—this would increase the acti-
vation energy required by the reaction, rather
than reducing it—but rather the binding of the
B. Enzyme-catalyzed reaction
transition state. This conclusion is supported
Shown here is a sequential mechanism in by the very high af nity of many enzymes for
which substrates A and B are bound and prod- analogues of the transition state (see p. 96). A
ucts C and D are released, in that order. An- simple mechanical analogy may help clarify
other possible reaction sequence, known as this (right). To transfer the metal balls (the
the “ping-pong mechanism,” is discussed on reactants) from location EA (the substrate
p. 94. state) via the higher-energy transition state
Enzymes are able to bind the reactants to EP (the product state), the magnet (the
(their substrates) specifically at the active cen- catalyst) has to be orientated in such a way
ter. In the process, the substrates are oriented that its attractive force acts on the transition
in relation to each other in such a way that state (bottom) rather than on EA (top).
they take on the optimal orientation for the
formation of the transition state (1–3). The
proximity and orientation of the substrates
therefore strongly increase the likelihood

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