Enzymes/properties

Increase rate of chemical reactions.

Most enzymes are proteins with diverse structure.
Functionally are biological catalysts:
Ribozymes are a class of RNA enzymes
Chemicals that increases the rate of a reaction.

Are not changed at the end of the reaction.

Do not change the nature of the reaction.

Lower the activation energy required.

 Nomenclature

Each enzyme is assigned two names. The first is its

short, recommended name, convenient for everyday
use.

The second is the more complete systematic name,

which is used when an enzyme must be identified
without ambiguity.
A. Recommended name

Most commonly used enzyme names have the suffix -ase attached to the substrate
of the reaction (for example, glucosidase, urease, sucrase), or to a description of the
action performed (for example, lactate dehydrogenase and adenylyl cyclase).

Some enzymes retain their original trivial names, which give no hint of the associated
enzymic reaction, for example, trypsin and pepsin.

B. Systematic name

The International Union of Biochemistry and Molecular Biology (IUBMB) developed a

system of nomenclature in which enzymes are divided into six major classes , each
with numerous subgroups.

The suffix -ase is attached to a fairly complete description of the chemical reaction
catalyzed, including the names of all the substrates; for example D-glyceraldehyde 3-
phosphate:NAD+ oxidoreductase.
Enzyme classification
 Properties of Enzymes

Specificity
Enzymes are usually highly specific as to which reactions they catalyze
and the substrates that are involved in these reactions.
Complementary shape, charge and hydrophilic/hydrophobic
characteristics of enzymes and substrates are responsible for this
specificity
Some of the enzymes showing the highest specificity and accuracy
are involved in the copying and expression of the genome.
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.
Catalytic efficiency

Most enzyme-catalyzed reactions are highly efficient, proceeding from 103 to

108 times faster than uncatalyzed reactions.

Typically, each enzyme molecule is capable of transforming 100 to 1,000

substrate molecules into product each second.

The number of molecules of substrate converted to product per enzyme

molecule per second is called the turnover number, or kcat.
Holoenzymes
Some enzymes require molecules other than proteins for enzymic activity.

Holoenzyme refers to the active enzyme with its nonprotein component,

whereas the enzyme without its nonprotein moiety is termed an
apoenzyme and is inactive.

If the nonprotein moiety is a metal ion such as Zn2+ or Fe2+, it is called a

cofactor.
If it is a small organic molecule, it is termed a coenzyme. Coenzymes that
only transiently associate with the enzyme are called cosubstrates.

Cosubstrates dissociate from the enzyme in an altered state (NAD+ and

coenzyme A ).

If the coenzyme is permanently associated with the enzyme and returned

to its original form, it is called a prosthetic group (FAD ).

Coenzymes frequently are derived from vitamins. For example, NAD+

contains niacin, coenzyme A contains pantothenic acid, and FAD contains
riboflavin.
 Regulation
Enzyme activity can be regulated, that is, enzymes can be activated or inhibited,
so that the rate of product formation responds to the needs of the cell.

Location within the cell

Many enzymes are localized in specific organelles within the cell. Such
compartmentalization serves to isolate the reaction substrate or product from
other competing reactions.
The intracellular location of some important biochemical pathways
 How Enzymes Work
The mechanism of enzyme action can be viewed from two different
perspectives.

The first treats catalysis in terms of energy changes that occur during the
reaction, that is, enzymes provide an alternate, energetically favorable
reaction pathway different from the uncatalyzed reaction.

The second perspective describes how the active site chemically facilitates
catalysis.
Effect of an enzyme on the activation energy of a reaction
energy changes and formation of an enzyme-substrate complex
 Active sites

Enzyme molecules contain a special pocket or cleft called the active site.

The active site contains amino acid side chains that create a three-
dimensional surface complementary to the substrate .

The active site binds the substrate, forming an enzymesubstrate (ES)

complex.

ES is converted to an enzymeproduct (EP) complex that subsequently

dissociates to enzyme and product
Active site

an enzyme with active site binding a substrate molecule.

 Role of active site

Transition-state stabilization: The active site often acts as a flexible molecular

template that binds the substrate in a geometric structure resembling the
activated transition state of the molecule .

By stabilizing the substrate in its transition state, the enzyme greatly increases
the concentration of the reactive intermediate that can be converted to
product and, thus, accelerates the reaction.
Other mechanisms: The active site can provide catalytic groups that
enhance the probability that the transition state is formed.

In some enzymes, these groups can participate in general acid-base

catalysis in which amino acid residues provide or accept protons.
In other enzymes, catalysis may involve the transient formation of a
covalent ES complex.
The mechanism of action of chymotrypsin,
an enzyme of protein digestion in the intestine, includes general base,
general acid, and covalent catalysis. A histidine at the active site of the
enzyme gains (general base) and loses (general acid) protons, mediated
by the pK of histidine in proteins being close to physiologic pH. Serine at
the active site forms a covalent link with the substrate.
Mechanism of Enzyme Action
Substrates have specific
shapes to fit into the
active sites
(Substrate fits into active
sites in enzyme.
Perfect fit may be induced:
Enzyme undergoes
structural change.

Enzyme-substrate complex
formed, then dissociates.

Products formed and

enzyme is unaltered.
Lock and key" model

Enzymes are very specific, and it was suggested by Emil Fischer in 1894 that this
was because both the enzyme and the substrate possess specific complementary
geometric shapes that fit exactly into one another. This is often referred to as "the
lock and key" model.

However, while this model explains enzyme specificity, it fails to explain the
stabilization of the transition state that enzymes achieve.

The "lock and key" model has proven inaccurate and the induced fit model is the
most currently accepted model.
Has static active site
Molecules fit into active site where
chemical change occurs no change in
the shape of the active site
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 continually
reshaped by interactions with the substrate as the substrate interacts with the
enzyme.
As a result, the substrate does not simply bind to a rigid active site, the amino
acid side chains which 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.

The active site continues to change until the substrate is completely bound, at
which point the final shape and charge is determined.
Often these molecules are flexible, and change shape when
an appropriate molecule binds to an active site. This is
known as an Induced Fit.
Factors Affecting Reaction Velocity

Enzymes can be isolated from cells, and their properties studied.

Different enzymes show different responses to changes in substrate

concentration, temperature, and pH.

Various physical and Chemical factors influence the reaction velocity of

enzymes.

Enzymatic responses to these factors give us valuable clues as to how

enzymes function in living cells.
Substrate concentration :(S)

Maximal velocity: The rate or velocity of a reaction (v) is the

number of substrate molecules converted to product per unit
time;
velocity is usually expressed as mol of product formed per
minute.

The rate of an enzyme-catalyzed reaction increases with

substrate concentration until a maximal velocity (Vmax) is
reached .

The leveling off of the reaction rate at high substrate

concentrations reflects the saturation with substrate of all
available binding sites on the enzyme molecules present.
Effect of substrate concentration on reaction velocity
Temperature
Increase of velocity with temperature: The reaction velocity increases with
temperature until a peak velocity is reached . This increase is the result of the
increased number of molecules having sufficient energy to pass over the
energy barrier and form the products of the reaction.

Decrease of velocity with higher temperature: Further elevation of the

temperature results in a decrease in reaction velocity as a result of
temperature-induced denaturation of the enzyme .
 pH
Effect of pH on the ionization of the active site: The concentration of H+ affects
reaction velocity in several ways. First, the catalytic process usually requires that the
enzyme and substrate have specific chemical groups in either an ionized or un-ionized
state in order to interact.

For example, catalytic activity may require that an amino group of the enzyme be in
the protonated form (NH3+). At alkaline pH, this group is deprotonated, and the rate
of the reaction, therefore, declines.

Effect of pH on enzyme denaturation: Extremes of pH can also lead to denaturation

of the enzyme, because the structure of the catalytically active protein molecule
depends on the ionic character of the amino acid side chains.

The pH optimum varies for different enzymes: The pH at which maximal enzyme
activity is achieved is different for different enzymes, and often reflects the [H+] at
which the enzyme functions in the body.

For example, pepsin, a digestive enzyme in the stomach, is maximally active at pH 2,

whereas other enzymes, designed to work at neutral pH, are denatured by such an
acidic environment.
Effect of pH on enzyme-catalyzed reactions