Enzymes

Chemical Nature of Enzymes

• All enzymes are globular proteins. They
have complex 3ry or 4ry structure in nature.
• With the exception of self-splicing
ribosomal RNA, all other enzymes are
protein in nature.
o The substance acted upon by the enzyme.
In-vivo reactions the energy barrier separates the reactants and
products (so preventing spontaneous uncontrolled reactions).
• Enzymatic reactions are 103 to 1017
times faster than the corresponding
un–catalyzed reactions.
Enzymes are superior to other
catalysts in several ways

1. Enzymes act at physiological temperatures.

2. Enzymes act in low ionic strength solution.
3. Enzymes act at near neutral pH.
4. Enzymes are highly specific with varying
degrees of specificity.
5. The activity of enzymes is closely regulated,
whereas the catalyst is difficulty to control.
 6.

Carbonic anhydrase catalysis the hydration of 106 CO2 molecules

per second which is 107 faster than spontaneous hydration.
1 2 3 4
 Enzyme Nomenclature
5. The International Union of Biochemistry (IUB) developed
a system of nomenclature in which enzymes are divided
into six major groups each with numerous sub-classes:

• The suffix “-ase” is attached to a fairly complete

description of the chemical reaction catalyzed, e.g.:

• D-glyceraldehyde-3-phosphate:NAD oxido-reductase.

• The IUB names are informative, but are sometimes too

cumbersome (‫ )ثقيل‬to be of general use.
 IUB Classification of Enzymes
No Group Name Type of Reaction Catalyzed

1 Oxidoreductases Oxidation–Reduction Reactions

2 Transferases Transfer of functional groups

3 Hydrolases Hydrolysis reactions

Addition to double bonds or its
4 Lyases
reverse
5 Isomerases Isomerization reactions
Ligases or Formation of bonds with ATP
6
Synthases cleavage into AMP + P~P.
Chemical Structure of Enzymes
• Enzymes are divided chemically into:

1. Simple protein enzymes: consisting only of proteins,

e.g. digestive enzymes: pepsin, maltase, etc...

2. Conjugated protein enzymes (Holoenzymes):

consisting of a protein part and a non–protein part.

• The protein part of the enzyme is heat labile and

known as apoenzyme.

• The non–protein part of the enzyme: Co–factor.

The non–protein part (Co–factor) can be:

A. Coenzymes (Co–substrate):
• They are non–protein, dialyzable,
thermolabile, organic part and loosely
attached to the protein part.

• It comes in full contact during the

activity of the enzyme.

• Coenzymes are vitamins or vitamin

derivatives and help enzyme catalysis.
The non–protein part (Co–factor) can be:

B. Prosthetic Group:
• It is an inorganic metal which is firmly attached to
the protein part. It is part of enzyme structure. e.g.:

1. Ascorbic acid oxidase contains copper.

2. Carbonic anhydrase & Matrix metalloproteinases

(MMPs) contain zinc.

3. Super oxide dismutase contains copper and zinc.

4. Cytochrome oxidase contains iron.

Forms of Enzymes

1. Zymogens.
2. Zymase.
3. Isoenzymes.
 Forms of Enzymes
1. Zymogens (Pro-enzymes or Pre-enzymes):

• Enzymes secreted as inactive form especially

proteolytic enzymes.

a) They are extracellularly.

b) Inactive to prevent destruction of the proteins of
the cells that synthesize them.

• The activation may involve the removal of a

polypeptide chain that is blocking or masking the
active site of the apoenzyme.
 Activation of Gastric Zymogen
1
 Proton activation:
H+
 Pepsinogen Pepsin + Peptide
(Proton)

2
 Autoactivation:
Pepsin
 Pepsinogen Pepsin + Peptide
(Auto-activation)
 Activation of Pancreatic Zymogens
3
 Enterokinase:
Enterokinase
 Trypsinogen Trypsin + Peptide
Kinase enzyme
4
 Proteolysis:
Trypsin
 Chymotrypsinogen Chymotrypsin
Proteolysis + Peptides
 Procarboxypeptidase Trypsin

Carboxypeptidase + Peptides
Trypsin
 Proelastase Elastase + Peptide
 Forms of Enzymes

2. Zymase:

• An enzyme that is secreted ready for

action, such as salivary amylase (Ptyalin).

3. Isoenzymes or isozymes:

• Enzymes that catalyze the same reaction

but differ in their physical properties,
chemical structure and activity,
i
Lactate Dehydrogenase (LDH)
Lactate Dehydrogenase (LDH)
Lactate DH in Heart & Muscles
Heart (H4) Muscle (M4)
LD1 LD5
H H M M
H H M M
Lactate DH in different tissues
H3M H2M2 HM3
LD2 LD3 LD4
H H H H H M
H M M M M M
Absolute
1
 2. Group Specificity
• Group or Relative specificity: The enzyme acts on
substances which are "similar" in structure &
posses the same type of bonds.

a) Lipase which hydrolyzes ester bonds of lipids

(Fatty acid with alcohol).

b) Trypsin hydrolyzes peptide bond whose –COOH

group belongs to one of the basic amino acids
only, (Tryptic fragments).
 2

C-
b)
 Enzyme Specificity
3. Absolute specificity: The enzyme acts on
ONE substrate only e.g. arginase, histidase,
urease, uricase, sucrase, maltase, lactase.
 4. Dual Specificity
• The enzyme may act upon:

a) Two different substrates by one and the

same mechanism (Xanthin oxidase).

b) Only one substrate by two different

mechanisms (Isocitrate Dehydrogenase).
4. Dual Specificity
4. Dual Specificity
 5. Stereo Specificity
a) Optical specificity:

• Enzymes of glycolysis act on D–sugars only.

• D-Amino acid oxidase and L–amino acid

oxidase.

b) Cis-trans specificity: e.g. fumarase enzyme

acts on trans form only (fumaric acid) but not
cis form (maleic acid).
 Optical specificity
1. L-Amino acid oxidase:

L-Amino acid -Keto acid + NH3

FMN FMNH2

2. D-Amino acid oxidase:

D-Amino acid -Keto acid + NH3

FAD FADH2
Cis-trans specificity
 Properties of the Enzymes

• Active sites:
• Enzyme molecules contain a special
pocket or cleft called the active site.

• The active site contains amino acid chains

that create a three dimensional structure
(Domain) complementary to the substrate.
Properties of the Enzymes

• Catalytic efficiency:
• Typically, each enzyme molecule is capable
of transforming 100 to 1000 substrate
molecules into product each second.

• The turnover number is the number of

molecules of substrate converted into
product per enzyme molecule per second.
 Location within the cell

• Enzymes are distributed among many

organelles within the cell.

1. Enzymes founds in the cell–membrane are

called (particulate) as adenyl cyclase.

2. Enzymes floating in the cytosol are called

(soluble), and some are found in the
mitochondria or in the nucleus.
HOW THE ENZYME WORK?
HOW THE ENZYME WORK?
 What is the mechanism of action?

• The mechanism of enzyme action

was explained by one of two theories:

1. Lock and key model.

2. Induced fit model.

 1

• This rigid template model is still useful for understanding

certain properties of enzymes as kinetics of simple substrate.
The “lock and key” Hypothesis
 Hexokinase
Or Glucokinase

Lock & Key Model of the Active Site

 2

o The substrate induces a conformational change in the active site of

the enzyme to fit the substrate.
Induced Fit Model of the Active Site
The “induced fit” model
Induced–Fit Theory