‫ جامع ة كرك وك‬/‫كلية طب االس نان‬ ‫محاضرات الكيمياء الحياتية‬

‫وال عبدهللا مرتضى‬ ‫ ن‬.‫د‬ ‫ة‬ ‫ة الثاني‬ ‫المرحل‬

Enzymes

Chemical Nature of Enzymes

All known enzymes are proteins. They are high molecular weight compounds
(biologic polymers) made up principally of chains of amino acids linked
together by peptide bonds. See Figure 1.

Enzymes catalyze the chemical reactions that make life as we know it

possible. It can be denatured and precipitated with salts, solvents and other
reagents. They have molecular weights ranging from 10,000 to 2,000,000.

Many enzymes require the presence of other compounds - cofactors - before

their catalytic activity can be exerted. This entire active complex is referred to
as the holoenzyme; i.e., apoenzyme (protein portion) plus the cofactor
(coenzyme, prosthetic group or metal-ion-activator) is called the holoenzyme.
Apoenzyme + Cofactor = Holoenzyme

Apo enzyme

Apo protein that forms an active enzyme system by combination with a

coenzyme and determines the specificity of this system for a substrate 

The cofactor may be:

1- A coenzyme - a non-protein organic substance which is dialyzable, thermo

stable and loosely attached to the protein part.

2- A prosthetic group - an organic substance which is dialyzable and thermo

stable which is firmly attached to the protein or apoenzyme portion.

3- A metal-ion-activator - these include K+, Fe++, Fe+++, Cu++, Co++, .Zn+

+, Mn++, Mg++, Ca++ and Mo +++.

Mode of action :

Enzymes enable chemical reactins to occur at cooler temperatures by reducing

the amount of activation energy required to break the bonds of the reactant
molecules. Each enzyme is very selective in the reaction it catalizes, this
feature is based on the ability of the enzyme to recognize the shape of the
certain reactant molecule - substrate. There is a special region on the enzyme
that has same shape and chemistry as the substrate, so the substrate fits
perfectly into tis docking station, the enzyme embraces it slightly and
catalyzes the reaction. When the product is released, the enzyme is ready to
accept another molecule of particular shape.

There are two common models of enzyme action. In the first model, the lock-
and-key model, a protein called an enzyme "the lock" binds with another
substance called a substrate "the key" and causes the lock to break down after
forming an enzyme-substrate complex. The model is so named because
substrates are very specific to individual enzymes. The second model is called
the induced-fit model. It is pretty much the same as the first, except it is
understood that the enzyme undergoes a conformational change before
binding with the substrate. Enzymes are able to facilitate reactions at lower
than usual temperatures because they lower the activation energy
requirements of many biological reactions, acting as organic catalysts. This
catalysis often requires "helper" substances called co-enzymes and cofactors.
The rate at which enzymes work is determined by the type of enzyme, the
amount of substrate present, and the amount of enzyme present. Some
molecules can inhibit enzyme function by imitating the substrate or causing
the enzyme to change shape.
Mechanism

Substrate binding
Enzymes must bind their substrates before they can catalyse any chemical
reaction. Enzymes are usually very specific as to what substrates they bind
and then the chemical reaction catalysed. Specificity is achieved by binding
pockets with complementary shape, charge and hydrophilic/hydrophobic
characteristics to the substrates. Enzymes can therefore distinguish between
very similar substrate molecules to be chemoselective, regioselective and
stereospecific.[26]

Some of the enzymes showing the highest specificity and accuracy are
involved in the copying and expression of the genome. Some of these
enzymes have "proof-reading" mechanisms. Here, an enzyme such as DNA
polymerase catalyzes a reaction in a first step and then checks that the product
is correct in a second step.[27] This two-step process results in average error
rates of less than 1 error in 100 million reactions in high-fidelity mammalian
polymerases.[1]:5.3.1 Similar proofreading mechanisms are also found in
RNA polymerase,[28] aminoacyl tRNA synthetases[29] and ribosomes.[30]

Conversely, some enzymes display enzyme promiscuity, having broad

specificity and acting on a range of different physiologically relevant
substrates. Many enzymes possess small side activities which arose
fortuitously (i.e. neutrally), which may be the starting point for the
evolutionary selection of a new function.[31][32]
Enzyme changes shape by induced fit upon substrate binding to form enzyme-
substrate complex. Hexokinase has a large induced fit motion that closes over
the substrates adenosine triphosphate and xylose. Binding sites in blue,
substrates in black and Mg2+ cofactor in yellow. (PDB: 2E2N, 2E2Q)

"Lock and key" model

To explain the observed specificity of enzymes, in 1894 Emil Fischer

proposed that both the enzyme and the substrate possess specific
complementary geometric shapes that fit exactly into one another.[33] This is
often referred to as "the lock and key" model.[1]:8.3.2 This early model
explains enzyme specificity, but fails to explain the stabilization of the
transition state that enzymes achieve.[34]

Induced fit model

In 1958, Daniel Koshland suggested a modification to the lock and key

model: since enzymes are rather flexible structures, the active site is
continuously reshaped by interactions with the substrate as the substrate
interacts with the enzyme.[35] As a result, the substrate does not simply bind
to a rigid active site; the amino acid side-chains that make up the active site
are molded into the precise positions that enable the enzyme to perform its
catalytic function. In some cases, such as glycosidases, the substrate molecule
also changes shape slightly as it enters the active site.[36] The active site
continues to change until the substrate is completely bound, at which point the
final shape and charge distribution is determined.[37] Induced fit may
enhance the fidelity of molecular recognition in the presence of competition
and noise via the conformational proofreading mechanism.[38

Specificity of Enzymes

One of the properties of enzymes that makes them so important as diagnostic

and research tools is the specificity they exhibit relative to the reactions they
catalyze. A few enzymes exhibit absolute specificity; that is, they will
catalyze only one particular reaction. Other enzymes will be specific for a
particular type of chemical bond or functional group. In general, there are four
distinct types of specificity:

Absolute specificity - the enzyme will catalyze only one reaction.

Group specificity - the enzyme will act only on molecules that have specific
functional groups, such as amino, phosphate and methyl groups.

Linkage specificity - the enzyme will act on a particular type of chemical

bond regardless of the rest of the molecular structure.

Stereochemical specificity - the enzyme will act on a particular steric or

optical isomer.

Though enzymes exhibit great degrees of specificity, cofactors may serve

many apoenzymes. For example, nicotinamide adenine dinucleotide (NAD) is
a coenzyme for a great number of dehydrogenase reactions in which it acts as
a hydrogen acceptor. Among them are the alcohol dehydrogenase, malate
dehydrogenase and lactate dehydrogenase reactions.
.