ENZYMES

Overview

Virtually all reactions in the body are mediated by enzymes, which are
protein catalysts that increase the rate of reactions without being
changed in the overall process.
Activation energy. . .decreased, rate of reaction speed up
The macromolecular components of almost all enzymes are composed
of protein, except for a class of RNA catalysts known as ribozymes
Enzymes are produced by cells and each cell will have its own
determined set of enzymes.

Compartmentalized – i.e. mitochondria, cytoplasm, lysosomes,

peroxisomes etc.

Enzymes only accelerate the reaction and do not initiate them.

Enzymes are found in all tissues and fluids of the body. Intracellular
enzymes catalyze the reactions of metabolic pathways

Plasma membrane enzymes regulate catalysis within cells in response

to extracellular signals

enzymes of the circulatory system are responsible for regulating the

clotting of blood
PROPERTIES OF ENZYMES
Enzymes are catalysts that increase the velocity of a chemical reaction,
and are not consumed during the reaction they catalyze

Some types of RNA can act like enzymes, RNAs with catalytic activity are
called ribozymes, and are much less commonly encountered than
protein catalysts
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 enzyme substrate (ES)
complex. ES is converted to an enzyme product (EP) complex that
subsequently dissociates to enzyme and product

Enzyme+Substrate. . . . .ES complex. .. . .EP complex. . product+Enzyme

The active site is not a passive receptacle for binding the substrate, but
rather is a complex molecular machine employing a diversity of
chemical mechanisms to facilitate the conversion of substrate to
product
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.
Specificity

Enzymes are highly specific, interacting with one or

a few substrates and catalyzing only one type of
chemical reaction.
Absolute specificity
Relative specificity
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

This provides a favorable environment for the reaction, and organizes

the thousands of enzymes present in the cell into purposeful pathways
Chemical nature
Protein in nature- are colloids, heat labile, have isoelectric pH values
Except ribozymes
On denaturation they lose their catalytic activity
Direction of enzyme reaction
Reversible
Irreversible
Proenzymes or Zymogens
Many enzymes are in the inactive state
Induction and repression of
enzymes
Constitutive enzymes

Regulatory enzymes
Holoenzymes
Some enzymes require molecules other than proteins for enzymic
activity

the enzyme without its nonprotein moiety is termed an Apo enzyme

and is inactive.
Complex enzymes are also known as holoenzymes

Holoenzyme refers to the active enzyme with its non-protein

component

In this the protein component is known as the apoenzyme

Holoenzyme= Apoenzyme+ non protein component

The non-protein component is known as the coenzyme or prosthetic
group.
Prosthetic group describes a complex in which the small organic
molecule is bound to the apoenzyme by covalent bonds
If it is a small organic molecule, it is termed a coenzyme.
Coenzymes that only transiently associate with the enzyme are called
co-substrates
when the binding between the apoenzyme and non-protein
components is non-covalent, the small organic molecule is called a
coenzyme.

Many prosthetic groups and coenzymes are water-soluble derivatives of

vitamins. Coenzymes frequently are derived from vitamins. For
example, NAD+ contains niacin, coenzyme A contains pantothenic acid,
and FAD contains riboflavin
If the non-protein moiety is a metal ion such as Zn2+ or Fe2+, it is called
a cofactor
 If the coenzyme is permanently associated with the enzyme and
returned to its original form, it is called a prosthetic group (FAD)
It should be noted that the main clinical symptoms of dietary vitamin
insufficiency generally arise from the malfunction of enzymes, which
lack sufficient cofactors derived from vitamins to maintain homeostasis.
Enzyme Classifications
Currently enzymes are grouped into six functional classes by the
International Union of Biochemists (I.U.B.).
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)
Enzymes are also classified on the basis of their composition.

Enzymes composed wholly of protein are known as simple enzymes in

contrast to complex enzymes, which are composed of protein plus a
relatively small organic molecule.
Classification Biochemical Properties
Oxidoreductases Act on many chemical groupings to add
or remove hydrogen atoms.
Transferases Transfer functional groups between
donor and acceptor molecules. Kinases
are specialized transferases that
regulate metabolism by transferring
phosphate from ATP to other
molecules.
Hydrolases Add water across a bond, hydrolyzing
it.
Lyases Add water, ammonia or carbon dioxide across
double bonds, or remove these elements to
produce double bonds.
Isomerases Carry out many kinds of isomerization: L to D
isomerizations, mutase reactions (shifts of
chemical groups) and others.
Ligases Catalyze reactions in which two chemical groups
are joined (or ligated) with the use of energy
from ATP.
MECHANISM OF ACTION
1. Formation of enzyme- substrate complex
2. Conversion of substrate to product
3. Release of product from the enzyme
LOCK AND KEY MODEL
Enzyme + substrate  enzyme-substrate complex

Bonds - hydrogen bonds, electrostatic bonds, covalent bonds, Vander

der wall’s forces
This model is now largely of historical interest because it does not take
into account an important property of proteins, namely their
conformational flexibility.
INDUCED FIT MODEL
Catalytic site is not rigid
Shows flexibility
Presence of substrate molecule induces a conformational change in the
enzyme molecule
The model takes into account the fact that proteins have some three-
dimensional flexibility.
The second model takes into account the fact that proteins have some
three-dimensional flexibility. According to this induced-fit model, the
binding of the substrate in- duces a conformational change in the
enzyme that results in a complementary