BIOMEDICAL IMPORTANCE

Enzymes are proteins that catalyze the chemical

reactions which make life as we know it possible.

The presence and maintenance of a complete and balanced

set of enzymes is essential for the breakdown of
nutrients to supply energy and chemical building
blocks; the assembly of those building blocks into proteins,
DNA, membranes, cells, and tissues; and the harnessing
of energy to power cell motility and muscle contraction.
 KLASIFIKASI & NOMENKLATUR
(IUBMB)
1. 6 KELAS
2. NAMA : SUBSTRAT(2) - JENIS REAKSI
3. (KETERANGAN TAMBAHAN)
4. NOMOR KODE SISTEMATIK

CONTOH: 1.1.1.37 L- MALAT : NAD+

OKSIDOREDUKTASE (DEKARBOKSILASI

L- MALAT + NAD+  PIRUVAT + CO2 + NADH + H+

 ENZYMES ARE CLASSIFIED BY REACTION
TYPE & MECHANISM
1. Oxidoreductases catalyze oxidations and
reductions.
Sred + S’ox ↔ Sox + S’red
(1.1.1.1 Alcohol : NAD oxidoreductase)
2. Transferases catalyze transfer of groups from a donor
molecule to an acceptor molecule.
S-G + S’ ↔ S + S’-G
(2.7.1.1 ATP : D-HEKSOSE 6 PHOSPHOTRANSFERASE)
3. Hydrolases catalyze the hydrolytic cleavage of C.C,
C.O, C.N, P.O, and certain other bonds, including acid
anhydride bonds.
(3.1.1.8 ACYLCHOLINE-ACYLHYDROLASE)
4. Lyases catalyze cleavage of C.C, C.O, C.N, and
other bonds by elimination, leaving double bonds, and
also add groups to double bonds.
X Y
-C–C- ↔ X–Y + -C–C–
(4.2.1.2 L MALAT HIDRO LYASE)
5. Isomerases catalyze geometric or structural changes
within a single molecule.
(5.1.1,1 ALANINE RACEMASE)
6. Ligases catalyze the joining together of two
molecules, coupled to the hydrolysis of a
pyrophosphoryl group in ATP or a similar nucleoside
triphosphate
(6.4.1.2 ACETYL- CoA : CO2 LIGASE)
 ENZYMES ARE CLASSIFIED BY
REACTION TYPE & MECHANISM
1. Oxidoreductases catalyze oxidations and reductions.
Sred + S’ox ↔ Sox + S’red
(1.1.1.1 Alcohol : NAD oxidoreductase)
2. Transferases catalyze transfer of groups from a donor
molecule to an acceptor molecule.
S-G + S’ ↔ S + S’-G
(2.7.1.1 ATP : D-HEKSOS6PHOSPHOTRANSFERASE)

3. Hydrolases catalyze the hydrolytic cleavage of C.C,

C.O, C.N, P.O, and certain other bonds, including acid
anhydride bonds.
(3.1.1.8 ACYLCHOLINE-ACYLHYDROLASE)
4. Lyases catalyze cleavage of C.C, C.O, C.N, and other
bonds by elimination, leaving double bonds, and also
add groups to double bonds.
X Y
-C–C- ↔ X–Y + -C–C–
(4.2.1.2 L MALAT HIDRO LYASE)
5. Isomerases catalyze geometric or structural changes within
a single molecule.
(5.1.1,1 ALANINE RACEMASE)

6. Ligases catalyze the joining together of two molecules,

coupled to the hydrolysis of a pyrophosphoryl group in ATP
or a similar nucleoside triphosphate
(6.4.1.2 ACETYL- CoA : CO2 LIGASE)
The enzyme classes
ENZYMES EMPLOY MULTIPLE MECHANISMS TO FACILITATE
CATALYSIS

Catalysis by Proximity

Acid-Base Catalysis

Catalysis by Strain

Covalent Catalysis
 CATALYSIS OCCURS AT THE ACTIVE SITE

• Termed the active site, this environment generally

takes the form of a cleft or pocket.

• The three-dimensional active site both shields substrates from

solvent and facilitates catalysis.

• Substrates bind to the active site at a region complementary to

a portion of the substrate that will not undergo chemical change
during the course of the reaction.
 FISHER’S:
Lock-and-Key Model of Enzyme-Substrate Binding
(Early in the last century)
 Daniel Koshland’s
Induced-Fit Model of Enzyme-Substrate
Binding
KEKHUSUSAN ENZIM

RELATIF

ABSOLUT
THREE POINT ATTACHMENT THEORY
PROSTHETIC GROUPS, COFACTORS & COENZYMES PLAY IMPORTANT
ROLES IN CATALYSIS

ORGANIC : COENZYMES
APOENZYME – COFACTOR
 INORGANIC : METALS
HOLOENZYME
 KOENZIM
I. PEMINDAHAN GUGUS BUKAN H+:
1. KoA
2. ASAM LIPOAT
3. TPP
4. B6 FOSFAT
5. FOLAT
6. BIOTIN
7. B12

II. PEMINDAHAN H+:

1. NAD+,NADP+
2. FMN, FAD
3. LIPOAT
4. KoQ
 proenzymes or zymogens

UNMASKING
PROENZYME ENZYME

CONTOH:
H+/ PEPSIN
PEPSINOGEN PEPSIN
ENTEROKINASE / TRIPSIN
TRIPSINOGEN TRIPSIN
TRIPSIN
KIMOTRIPSINOGEN KIMOTRIPSIN

Proenzymes facilitate rapid mobilization of an activity in response to

physiologic demand
 NUMEROUS FACTORS AFFECT
THE REACTION RATE

SUBSTRATE CONCENTRATION
ENZYME CONCENTRATION
TEMPERATURE
pH
OTHERS: ACTIVATORS
INHIBITORS
OXIDATION/REDUCTION
RADIATION
Enzymes Decrease the Activation Energy
The progress curve for an enzymatic reaction in
which the substrate S is converted into products
 An enzymecatalyzed
reaction reaches a maximal velocity
THE RATE OF CATALYSIS

(1)

(2)

(3)

(4)
(5)
 (6)

(7)

(8)

KM called the Michaelis constant:

Note that KM has the units of concentration

Inserting equation 8 into equation 7 and solving for [ES] yields

(9)
The concentration of uncombined enzyme [E] is
(10)

Substituting this expression for [E] in equation 9 gives

(11)

(12)

(13)
By substituting this expression for [ES] into equation 3:

(14)

The maximal rate, V max, is attained when [ES] = [E]T. Thus,

(15)

Substituting equation 15 into equation 14 yields

the Michaelis-Menten equation:

(16)
The Michaelis-Menten Equation

Bagaimana harga v bila:

1: S ↓↓
2: S = Km
3: S ↑↑
 Effect of substrate concentration on the
initial velocity of an enzyme-catalyzed reaction
EFFECT OF ENZYME CONCENTRATION

vi

[E]
Temperature Dependency of Enzyme Activity
pH Dependency of Enzyme Activity
Effect of pH on Enzyme Activity
 ENZYME MODIFIERS

ORGANIC : COENZYMES
POSITIVE
INORGANIC: COFACTORS

ORGANIC : INHIBITORS
NEGATIVE
INORGANIC: Hg, Pb, Ag
 INORGANIC MODIFIERS

METALS

* POSITIVE : Fe, Mn, Mg, Cu, Ca, Zn, Co

* NEGATIVE : Hg, Ag, Pb

 ORGANIC MODIFIERS

INHIBITORS
1. COMPETITIVE INHIBITION
EI
+I

+S
ES E + P
2. NON COMPETITIVE INHIBITION

2.1 REVERSIBLE
EI
+I +S
E EIS EI + P

+S ES +I

E + P

2.2 IRREVERSIBLE
- TOXINS : iodoasetate
- OXIDATORS/REDUCTORS
- HEAVY METALS
Kinetics of Inhibition
Distinction Between a Competitive and a
Noncompetitive Inhibitor
Double-reciprocal or Lineweaver–Burk plot of 1/v vs 1/ [S]. The intercept
on the vertical axis gives 1/Vmax and the slope gives Km /Vmax. The
intercept on the horizontal axis equals –1/Km.
 .
Kinetics of a Competitive Inhibitor
Effect of a Competitive Inhibitor
Kinetics of a Nonccompetitive Inhibitor
 Non Competitive Inhibition

+ inhibitor
1/v

without inhibitor

-1/VM

-1/KM 1/[S]
 ALLOSTERIC ENZYME

D acts as a negative allosteric effector of Enz1

 PENGHAMBATAN ALLOSTERIK

INHIBITOR
INHIBITOR

SISI ALLOSTERIK

PERUBAHAN
KONFORMASI
SISI AKTIF
SUBSTRAT

ENZIM
SUBSTRAT
Sites of Feedback Inhibition in a
Branched Biosynthetic Pathway
Multiple Feedback Inhibition
 FUNGSI DIAGNOSTIK

FUNGSIONAL
ENZIM PLASMA/ CHE (3.1.1.8)
SERUM Lipase (3.1.1.3)

NON FUNGSIONAL

SEKRETORIK INTRASEL
 Amilase (3.2.1.1) AST (2.6.1.1)
Lipase (3.1.1.3) ALT (2.6.1.2)
 Principal serum enzymes used in clinical diagnosis.
Many of the enzymes are notspecific for the disease listed.