Enzymes
Definition
Enzymes are very efficient catalysts for biochemical reactions. They
speed up reactions by providing an alternative reaction pathway of
lower activation energy.
Nomenclature of enzymes
Each enzyme is assigned two names:
A. Recommended name:
It is Convenient for everyday use.
1- For hydrolases = name of substrate+ase
Example: .urease, lipase, sucrase, ...
2-For other enzymes:
name of substrate + mechanism of action + ase
e.g. succinic dehydrogenase, lactate dehydrogenase, etc..
• 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 IUBMB names are informative, but are sometimes too
complicated to be of general use.
Composition of Enzymes:
• All enzymes are protein in nature. They are divided
chemically into:
1. Simple protein enzymes: consisting wholly of proteins,
e.g. pepsin, maltase etc..
2. Conjugated protein enzymes (Holoenzymes): consisting
of protein part and non protein part. The protein part
of the enzyme is heat labile and known as apoenzyme.
The non protein part is known as cofactor.
Cofactors
• They are inorganic substances that are required for, or increase the
rate of catalysis.
• They are loosely attached to the protein part of the enzyme
• Examples: Zn++, Fe++, Fe+++
Coenzymes
• They are specific type of cofactors which are organic molecules
that are required by certain enzymes to carry out catalysis.
• They bind to the active site of the enzyme and participate in
catalysis but are not considered substrates of the reaction.
• Coenzymes often function as intermediate carriers of electrons,
specific atoms or functional groups that are transferred in the overall
reaction.
• Examples: usually made from vitamins such as NAD, NADP
Prosthetic groups
• They are cofactors that bind tightly to proteins or enzymes.
• They can be organic or metal ions and are often attached to
proteins by a covalent bond.
Holoenzyme
• An enzyme that requires a helper group and isn't complete
without it. Once attached, it's called a holoenzyme.
• A holoenzyme is an enzyme with any metal ions or coenzymes
attached to it that is now ready to catalyze a reaction.
Types of coenzymes
1. For transfer of hydrogen:
Nicotinamide nucleotides: e.g. NAD+ and NADP+.
Flavin nucleotides e.g. FAD and FMN.
Glutathione (G-SH).
2. For transfer of groups other than hydrogen:
– L-Ascorbic acid.
– Vitamin K.
– Tetrahydrofolic acid (FH4, THFA).
Zymogens (Proenzymes):
• Enzymes secreted in inactive form especially proteolytic enzymes
to prevent destruction of the proteins of the cells that synthesize
them.
• Activation of zymogen takes place either by:
[Link] Changes: pepsinogen HCL pepsin.
trypsin
[Link]: Trypsinogen trypsin.
Enterokinase
[Link]: trypsinogen trypsin.
• The mechanism of activation may involve unmasking of a
polypeptide chain that may be blocking or masking the active
centre of the apoenzyme.
Isoenzymes or isozymes:
Enzymes that catalyze the same reaction but differ in their structure,
properties and activity.
• Examples:
1- Lactate dehydrogenase (LDH) in plasma which by electrophoresis
is separated into 5 isoenzymes. LDH molecule consists of 4
polypeptide chains; each may be H or M type.
Thus the 5 isoenzymes are called LDH 1, 2, 3, 4 and 5. LDH1 (HHHH)
is produced by heart, LDH5 (MMMM) is produced by muscles and
liver and other isoenzymes are produced by other tissues.
2- creatine kinase (CK) occurs as three isoenzymes.
Each isoenzyme is a dimer composed of two polypeptides
called B and M subunits. CK1=BB, CK2=MB and CK3=MM
Properties of the enzymes:
1- Enzyme specificity
2- Active sites
3- Catalytic efficiency
4- Location within the cell
1- Enzyme specificity:
• Enzymes have high specificity as they catalyze only one
reaction or a small group of related reactions.
• Specificity of enzymes is due to the nature and
arrangement of the chemical groups at catalytic site.
• This allows the enzyme to unite with and activate only
one substrate or a small number of structurally related
substrates.
There are 4 types of specificity:
A- Absolute specificity: The enzyme acts only on one
substrate.
B- Group specificity: The enzyme will act only on molecules
that have specific functional groups, such as amino,
phosphate and methyl groups.
Examples:
• Maltase hydrolyzes glucosidic linkage attaching on one
side of glucose
C- Linkage specificity: the enzyme will act on a particular
type of chemical bond regardless of the rest of the
molecular structure.
D- Stereo specificity: Includes:
1- Optical specificity: Enzymes of glycolysis act on
D-sugars only.
2- Cis-trans specificity: e.g. fumarase enzyme acts
on fumaric acid but not maleic acid.
[Link] sites:
• Enzyme molecules contain a special pocket or cleft called the active
site.
• It is the site where substrate molecules bind and undergo a
chemical reaction
[Link] efficiency:
• Each enzyme molecule is capable of transforming 100 to 1000
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.
[Link] within the cell:
Many enzymes are localized in specific organelles within the cell.
Mechanisms of enzyme action:
• For two molecules to react they must collide with one
another.
• They must collide in the right direction (orientation) and
with sufficient energy.
• Sufficient energy means that they have enough energy to
overcome the energy barrier to reaction. This is called the
activation energy.
.
• Enzymes have an active site. This is part of the molecule
that has just the right shape and functional groups to bind
to one of the reacting molecules. The reacting molecule
that binds to the enzyme is called the substrate.
• The enzyme and substrate form a reaction intermediate. Its
formation has a lower activation energy than the reaction
between reactants without a catalyst
The active site of enzyme unites with the substrate by
many mechanisms:
1. Lock and key model (rigid template) :
• This is the simplest model to represent how an enzyme
works.
• The substrate simply fits into the active site to form a
reaction intermediate
2. Induced fit model:
• In this model the enzyme molecule changes shape as
the substrate molecules gets close.
• The change in shape is 'induced' by the approaching
substrate molecule.
• This more sophisticated model relies on the fact that
molecules are flexible because single covalent bonds
are free to rotate.
Factors which affect enzyme activity:
1. Nature of the Enzyme (Isoenzymes).
2. Substrate Concentration :
The rate of an enzyme catalyzed reaction
increases with substrate
concentration until a maximal velocity
(Vmax) is reached.
The leveling of the reaction rate at
high substrate concentrations reflects
the saturation with substrate of all
available binding sites on the enzyme.
3. Temperature:
• The reaction velocity increases with temperature until a peak
velocity is reached. This increase is due to the increased number of
molecules having sufficient energy to pass over the energy barrier
and form the products of the reaction.
• Further elevation of the temperature results in a decrease in
reaction velocity as a result of
temperature-induced
denaturation of the enzyme.
4. pH:
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.
•The most favorable pH value - the
point where the enzyme is most
active - is known as the optimum
pH.
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.
The concentration of H+ affects reaction velocity in several ways:
1. Achievement of ionized or unionized state of active site of the
enzyme and substrate required for their action.
2. Extremes of pH can lead to denaturation of the enzyme.
5. Enzyme Concentration:
The velocity the reaction is directly proportional to the
concentration of the enzyme. Further increase in the enzyme
concentration will not increase the velocity of the reaction
(within limit).
6. Concentration of Reaction Products:
When the products of the reaction are removed as fast as they are
formed, the reaction would be 100% complete.
7. Effect of Time:
As the reaction proceeds, the velocity of the reaction decreases
due to decreased concentration of substrate, and increased
concentration of products, which tend to reverse.
8. Activators:
They are inorganic ions which increase the activity of enzyme.
Chloride ions activate amylase, magnesium ions activate kinases
and calcium ions activate thrombokinase.
9. Inhibitors:
The activity of enzymes is inversely proportional to inhibitor
concentration
