Enzymes

Enzymes, are the most extraordinary 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
substrates,
they
accelerate
chemical
reactions
tremendously,
and they function in aqueous solutions under
very mild conditions of temperature and pH.
Few nonbiological catalysts have all these
properties.

 Enzymes accelerate reactions by factors of as

much as a million or more.
Indeed, most reactions in biological systems do
not take place at observable rates in the
absence of enzymes.
Even a reaction as simple as the hydration of
carbon dioxide is catalyzed by an enzyme
namely, carbonic anhydrase.
The transfer of CO2 from the tissues into the
blood and then to the alveolar (air sac in the
lung) air would be less complete in the absence
of this enzyme.
In fact, carbonic anhydrase is one of the fastest
enzymes known. Each enzyme molecule can
hydrate 106 molecules of CO2 per second.

 This catalyzed reaction is 107 times as fast as

the uncatalyzed one.
Enzymes are highly specific both in the
reactions that they catalyze and in their
choice of reactants, which are called
substrates.
An enzyme usually catalyzes a single chemical
reaction or a set of closely related reactions.
Side reactions leading to the wasteful
formation of by-products are rare in enzymecatalyzed reactions, in contrast with
uncatalyzed ones.

 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 precursors.
Through the action of regulatory enzymes,
metabolic pathways are highly coordinated
to yield a tuneful interplay among the
many activities necessary to sustain life.

 The study of enzymes has immense

practical importance.
In some diseases, especially inheritable
genetic disorders, there may be a
deficiency or even a total absence of one
or more enzymes.
For other disease conditions, excessive
activity of an enzyme may be the cause.
Measurements of the activities of enzymes
in
blood plasma, erythrocytes, or tissue
samples are important in diagnosing certain
illnesses.

 Many drugs exert their biological

effects through interactions with
enzymes. And enzymes are
important practical tools, not only in
medicine but in the chemical
industry, food processing, and
agriculture.

History of Enzyme
Biological catalysis was first recognized
and described in the late 1700s, in studies
on the digestion of meat by secretions of
the stomach, and research continued in
the 1800s with examinations of the
conversion of starch to sugar by saliva and
various plant extracts.
In the 1850s, Louis Pasteur concluded that
fermentation of sugar into alcohol by yeast
is catalyzed by ferments.

 He postulated that these ferments

were inseparable from the structure
of living yeast cells
Then in 1897 Eduard Buchner
discovered that yeast extracts could
ferment sugar to alcohol, proving that
fermentation was promoted by
molecules that continued to function
when removed from cells
Frederick W. Khne called these
molecules enzymes.

 The isolation and crystallization of urease

by James Sumner in 1926 provided a
breakthrough in early enzyme studies.
Sumner found that urease crystals consisted
entirely of protein, and he postulated that
all enzymesare proteins.
In the absence of other examples, this idea
remained controversial for some time.
Only in the 1930s was Sumners conclusion
widely accepted, after John Northrop and
Moses Kunitz crystallized pepsin, trypsin,
and other digestive enzymes and found
them also to be proteins

 With the exception of a small group of catalytic

RNA molecules , all enzymes are proteins.
Their catalytic activity depends on the integrity
of their native protein conformation.
If an enzyme is denatured or dissociated into its
subunits, catalytic activity is usually lost.
If an enzyme is broken down into its component
amino acids, its catalytic activity is always
destroyed.
Thus the primary, secondary, tertiary, and
quaternary structures of protein enzymes are
essential to their catalytic activity.

 Enzymes, like other proteins, have

molecular
weights ranging from about 12,000 to
more than 1 million.
Some enzymes require no chemical
groups for
activity other than their amino acid
residues. Others require an additional
chemical component called a cofactor
either one or more inorganic
ions, such as Fe2+, Mg2+, Mn2+, or Zn2+

 A complex organic or metalloorganic molecule called a

coenzyme
OR Cofactors that are small organic molecules are called
coenzymes.

 Coenzymes are often derived from vitamins, it can

be either tightly or loosely bound to the enzyme.
If tightly bound, they are called prosthetic groups.
Loosely associated coenzymes are more like
cosubstrates because they bind to and are
released from the enzyme just as substrates and
products are.

The use of the same coenzyme by a variety of

enzymes and their source in vitamins sets
coenzymes apart from normal substrates,

However, enzymes that use the same coenzyme

are usually mechanistically similar

Classification of enzyme
Enzymes Are Classified on the Basis of the
Types of Reactions That They Catalyze
To bring some consistency to the
classification of enzymes, in 1964 the
International Union of Biochemistry
established an Enzyme Commission to
develop a nomenclature for enzymes.
Reactions were divided into six major
groups
numbered 1 through 6

 These groups were subdivided and further subdivided,

so that a four-digit number preceded by the letters EC
for Enzyme Commission could precisely identify all
enzymes

 Consider as an example nucleoside monophosphate

(NMP) kinase. It catalyzes the following reaction:

NMP kinase transfers a phosphoryl group from ATP to NMP to

form a nucleoside diphosphate (NDP) and ADP
Consequently, it is a transferase, or member of group 2. Many
groups in addition to phosphoryl groups, such as sugars and
carbon units, can be transferred.
Transferases that shift a phosphoryl group are designated 2.7.
Various functional groups can accept the phosphoryl group. If a
phosphate is the acceptor, the transferase is designated 2.7.4.
The final number designates the acceptor more precisely.
In regard to NMP kinase, a nucleoside monophosphate is the
acceptor, and the enzyme's designation is EC 2.7.4.4.
Although the common names are used routinely, the
classification number is
used when the precise identity of the enzyme might be

Kinetics of enzyme catalyzed

reactions
The formation of an enzyme-substrate complex is the
first step in enzymatic catalysis
Emil Fischer's proposed the lock and key model in
1890, in this model the active site of the unbound
enzyme is complementary in shape to the substrate

Induced-Fit Model of Enzyme-Substrate

Binding
In this model, the enzyme changes shape on
substrate
binding.
The active site forms a shape complementary to the
substrate only after the substrate has been bound.

Evidences for the existence of an

enzyme-substrate complex
At a constant concentration of enzyme, the
reaction rate increases with increasing substrate
concentration until a maximal velocity is reached.
In contrast, uncatalyzed reactions do not show
this saturation effect. The fact that an enzymecatalyzed reaction has a maximal velocity
suggests the formation of a distinct ES complex

 X-ray crystallography has provided

high-resolution images of substrates
and substrate analogs bound to the
active sites of many enzymes

Spectroscopic characteristics of many enzymes and

substrates change on formation of an ES complex
Tryptophan synthetase, a bacterial enzyme that
contains a pyridoxal phosphate (PLP) prosthetic group.
This enzyme catalyzes the synthesis of l-tryptophan from
l-serine and indole-derivative.
The addition of l-serine to the enzyme produces a
marked increase in the fluorescence of the PLP group
The subsequent addition of indole, the second
substrate, reduces this fluorescence to a level even
lower than that of the enzyme alone.

Active site
The active site of an enzyme is the region
that binds the substrates (and the
cofactor, if any).
It also contains the residues that directly
participate in the making and breaking of
bonds. These residues are called the
catalytic groups.
Thus, the interaction of the enzyme and
substrate at the active site promotes the
formation of the transition state

 The active site is a three-dimensional

cleft formed by groups that come from
different parts of the amino acid
sequence indeed, residues far apart in
the sequence may interact more strongly
than adjacent residues in the amino
acid sequence. In lysozyme, an enzyme
that degrades the cell walls of some
bacteria, the important groups in the
active
site are contributed by residues
numbered 35, 52, 62, 63, 101, and 108 in
the sequence of the 129 amino acids